Long-term Treatments Research Articles

Unraveling the potential of Cu addition and cluster hardening in Al-Mg-Si alloys

With the aim of further exploiting the trade-off between formability and strength in Al alloys, this study addresses the influence of Cu in Al-Mg-Si alloys that achieve simultaneously high strength and high ductility via cluster hardening. The study carefully examines the mechanical properties and strain hardening behavior of various Mg/Si ratios with and without Cu and compares the effects of pre-aging and atypical long-term low-temperature aging treatments at 100°C to conventional heat treatments. Interestingly, in all cases adding Cu improved ductility. In the extremal case cluster hardening plus the addition of Cu quadruples elongation, while keeping yield strength similar to the classical T6 state. The results of the study are discussed with a focus on the dense distribution of clusters and partial hardening phases based on atom probe tomography data. Most importantly, the cluster-hardened alloys exhibit pronounced strain-hardening properties, which we evaluate using a Kocks-Mecking approach in combination with a microstructural analysis in the pre-aging and long-term aging condition. The key finding of the study involves the role of Cu in refining clusters/precipitates, where it causes a substantial increase in number density and volume fraction. This refinement, in combination with strain-induced clustering, contributes significantly to improving the alloys’ overall mechanical performance and underlines the central role of Cu in tailoring microstructural features, especially in alloys primarily strengthened by clusters.

Energy-Dispersive X-Ray Microanalysis – as a Method for Study the Aluminium-Polysilicon Interface after Exposure with Long-Term and Rapid Thermal Annealing

Energy dispersive X-ray microanalysis is one of the main methods for determining the elemental composition of matter. Possessing high locality and a relatively shallow penetration depth of the electron beam (< 1 μm), this method has found wide application in the field of microelectronics, as the main method for analyzing the elemental composition of matter. The method allows to study the surface of a substance both pointwise and over an area with the construction of element distribution maps. In the paper we investigated the influence of long-term and rapid heat treatments on the formation of the aluminum-polysilicon interface in order to study the formation of ohmic contacts in the element base of integrated circuits. The aluminumpolysilicon interface was studied using energy-dispersive X-ray microanalysis. It has been established that during long-term thermal annealing (450 °C, 20 min) polysilicon is completely dissolved in aluminum followed by its segregation in the form of separate agglomerates in the aluminum film, which can lead to a complete failure of the integrated circuit. During rapid thermal annealing (450 °C, 7 s) such a phenomenon was not detected. Thus it is advisable to use rapid thermal annealing as an alternative to traditional long-term thermal annealing in microelectronics. This makes it possible to significantly reduce the dissolution of polysilicon in aluminum, avoid the destruction of ohmic contacts and increase the percentage of yield of workable 0products in the process of integrated circuits' manufacturing.

In Vitro Toxicity Evaluation of Some Plant Extracts and Their Potential Application in Xerosis cutis

Xerosis cutis represents one of the most common dermatological diagnoses, which, when untreated, can be the trigger for open wounds, infections, and other skin diseases. Plant extracts are a valuable option for long-term treatments for xerosis due to their phytocompounds, especially polyphenols, flavonoids, triterpenes, and polysaccharides, with antioxidant, anti-inflammatory, antimicrobial, moisturizing, and reparatory effects. Active substances have different mechanisms; therefore, evaluating the effects on the cells can be a key indicator, providing valuable information in terms of both cytotoxicity and efficacy. The in vitro and in vivo toxicity tests performed for Betulae extractum, Liquiritiae extractum, and Avenae extractum highlighted potential toxic effects at higher concentrations in a dose-dependent relationship, but at lower levels they can be considered safe (12.5 µg/mL for birch and licorice extracts, 50 µg/mL for oat extract). Concerning the re-epithelialization process, the results revealed that all three dry extracts effectively stimulate skin cell migration, highlighting a potential anti-inflammatory effect by increasing the cell migration rate in conditions of induced inflammation associated with oxidative stress. Among the tested concentrations with a potential contribution to wound healing, the following standout: are birch bark extract 3 μg/mL, licorice root extract 7.5 µg/mL, and oat herb (harvested before flowering) extract 7.5 µg/mL.

Acceptance of AI in Health Care for Short- and Long-Term Treatments: Pilot Development Study of an Integrated Theoretical Model.

As digital technologies and especially artificial intelligence (AI) become increasingly important in health care, it is essential to determine whether and why potential users intend to use related health information systems (HIS). Several theories exist, but they focus mainly on aspects of health care or information systems, in addition to general psychological theories, and hence provide a small number of variables to explain future behavior. Thus, research that provides a larger number of variables by combining several theories from health care, information systems, and psychology is necessary. This study aims to investigate the intention to use new HIS for decisions concerning short- and long-term medical treatments using an integrated approach with several variables to explain future behavior. We developed an integrated theoretical model based on theories from health care, information systems, and psychology that allowed us to analyze the duality approach of adaptive and nonadaptive appraisals and their influence on the intention to use HIS. We applied the integrated theoretical model to the short-term treatment using AI-based HIS for surgery and the long-term treatment of diabetes tracking using survey data with structured equation modeling. To differentiate between certain levels of AI involvement, we used several scenarios that include treatments by physicians only, physicians with AI support, and AI only to understand how individuals perceive the influence of AI. Our results showed that for short- and long-term treatments, the variables perceived threats, fear (disease), perceived efficacy, attitude (HIS), and perceived norms are important to consider when determining the intention to use AI-based HIS. Furthermore, the results revealed that perceived efficacy and attitude (HIS) are the most important variables to determine intention to use for all treatments and scenarios. In contrast, abilities (HIS) were important for short-term treatments only. For our 9 scenarios, adaptive and nonadaptive appraisals were both important to determine intention to use, depending on whether the treatment is known. Furthermore, we determined R² values that varied between 57.9% and 81.7% for our scenarios, which showed that the explanation power of our model is medium to good. We contribute to HIS literature by highlighting the importance of integrating disease- and technology-related factors and by providing an integrated theoretical model. As such, we show how adaptive and nonadaptive appraisals should be arranged to report on medical decisions in the future, especially in the short and long terms. Physicians and HIS developers can use our insights to identify promising rationale for HIS adoption concerning short- and long-term treatments and adapt and develop HIS accordingly. Specifically, HIS developers should ensure that future HIS act in terms of HIS functions, as our study shows that efficient HIS lead to a positive attitude toward the HIS and ultimately to a higher intention to use.

Green light mediates atypical photomorphogenesis by dual modulation of Arabidopsis phytochromes B and A.

Although green light (GL) is located in the middle of the visible light spectrum and regulates a series of plant developmental processes, the mechanism by which it regulates seedling development is largely unknown. In this study, we demonstrated that GL promotes atypical photomorphogenesis in Arabidopsis thaliana via the dual regulations of phytochrome B (phyB) and phyA. Although the Pr-to-Pfr conversion rates of phyB and phyA under GL were lower than those under red light (RL) in a fluence rate-dependent and time-dependent manner, long-term treatment with GL induced high Pfr/Pr ratios of phyB and phyA. Moreover, GL induced the formation of numerous small phyB photobodies in the nucleus, resulting in atypical photomorphogenesis, with smaller cotyledon opening angles and longer hypocotyls in seedlings compared to RL. The abundance of phyA significantly decreased after short- and long-term GL treatments. We determined that four major PHYTOCHROME-INTERACTING FACTORs (PIFs: PIF1, PIF3, PIF4, and PIF5) act downstream of phyB in GL-mediated cotyledon opening. In addition, GL plays opposite roles in regulating different PIFs. For example, under continuous GL, the protein levels of all PIFs decreased, whereas the transcript levels of PIF4 and PIF5 strongly increased compared with dark treatment. Taken together, our work provides a detailed molecular framework for understanding the role of the antagonistic regulations of phyB and phyA in GL-mediated atypical photomorphogenesis.

Organic fertilisation enhances network complexity among bacteria, fungi, and protists by improving organic matter and phosphorus in acidic agricultural soils

Research has explored the impact of organic fertilisation on improving agroecosystem productivity and resilience, highlighting the significant contributions of protists in addition to bacteria and fungi. However, the interactions among bacteria, fungi and protists in organically fertilised soils remain largely unknown. In this study, soil samples were collected from four long-term fertilisation treatments: no fertilisation (Control), inorganic fertilisation (NPK), organic fertilisation (OM), and combined inorganic and organic fertilisation (NPKOM). The abundance and composition of bacteria, fungi, and protist communities, as well as co-occurrence networks, were analysed under different fertilisation treatments. Our results showed that the total abundance of bacteria, fungi, and protists increased by a minimum of 2.95, 3.47, and 0.66 times, respectively, after organic fertiliser application. Moreover, the application of organic fertilisers significantly altered the structures of soil microbial communities by enriching bacterial Proteobacteria and Actinobacteria, fungal Ascomycota, and protist Conosa. Changes in the total abundance of bacteria, fungi, and protists, and their community structures in soils with organic fertilisers were associated with increases in soil organic carbon and phosphorous. Additionally, microbial networks exhibited greater complexity in organically fertilised soils than in non-organically fertilised soils by possessing higher linkage density. The increased complexity may be attributed to potential interkingdom associations among bacteria, fungi, and protists in high soil organic carbon and phosphorus. These results highlight that the application of organic fertilisers has the potential to enhance the complexity of microbial coexistence in acidic agricultural soils.

Application of Silicone in Ophthalmology: A Review.

This paper reviews the latest trends and applications of silicone in ophthalmology, especially related to intraocular lenses (IOLs). Silicone, or siloxane elastomer, as a synthetic polymer, has excellent biocompatibility, high chemical inertness, and hydrophobicity, enabling wide biomedical applications. The physicochemical properties of silicone are reviewed. A review of methods for mechanical and in vivo characterization of IOLs is presented as a prospective research area, since there are only a few available technologies, even though these properties are vital to ensure medical safety and suitability for clinical use, especially if long-term function is considered. IOLs represent permanent implants to replace the natural lens or for correcting vision, with the first commercial foldable lens made of silicone. Biological aspects of posterior capsular opacification have been reviewed, including the effects of the implanted silicone IOL. However, certain issues with silicone IOLs are still challenging and some conditions can prevent its application in all patients. The latest trends in nanotechnology solutions have been reviewed. Surface modifications of silicone IOLs are an efficient approach to further improve biocompatibility or to enable drug-eluting function. Different surface modifications, including coatings, can provide long-term treatments for various medical conditions or medical diagnoses through the incorporation of sensory functions. It is essential that IOL optical characteristics remain unchanged in case of drug incorporation and the application of nanoparticles can enable it. However, clinical trials related to these advanced technologies are still missing, thus preventing their clinical applications at this moment.

Plant roots affect free-living diazotroph communities in temperate grassland soils despite decades of fertilization

Fixation of atmospheric N2 by free-living diazotrophs accounts for an important proportion of nitrogen naturally introduced to temperate grasslands. The effect of plants or fertilization on the general microbial community has been extensively studied, yet an understanding of the potential combinatorial effects on the community structure and activity of free-living diazotrophs is lacking. In this study we provide a multilevel assessment of the single and interactive effects of different long-term fertilization treatments, plant species and vicinity to roots on the free-living diazotroph community in relation to the general microbial community in grassland soils. We sequenced the dinitrogenase reductase (nifH) and the 16S rRNA genes of bulk soil and root-associated compartments (rhizosphere soil, rhizoplane and root) of two grass species (Arrhenatherum elatius and Anthoxanthum odoratum) and two herb species (Galium album and Plantago lanceolata) growing in Austrian grassland soils treated with different fertilizers (N, P, NPK) since 1960. Overall, fertilization has the strongest effect on the diazotroph and general microbial community structure, however with vicinity to the root, the plant effect increases. Despite the long-term fertilization, plants strongly influence the diazotroph communities emphasizing the complexity of soil microbial communities’ responses to changing nutrient conditions in temperate grasslands.

Physiologically-Based Pharmacokinetic Modeling and In Vitro-In Vivo Correlation of TV-46000 (Risperidone LAI): Prediction from Dog to Human.

The interest in the development and therapeutic application of long-acting injectable products for chronic or long-term treatments has experienced exponential growth in recent decades. TV-46000 (Uzedy, Teva) is a long-acting subcutaneous (sc) injectable formulation of risperidone, approved for the treatment of schizophrenia in adults. Following sc injection, the copolymers together with risperidone precipitate to form a sc depot under the skin to deliver therapeutic levels of risperidone over a prolonged period of either 1 month or 2 months, depending upon the dose. This work presents the strategy and the results of the physiologically-based pharmacokinetic (PBPK) modeling and establishing of in vitro-in vivo correlation (IVIVC) for the prediction of TV-46000 pharmacokinetic profile in humans, using in vitro release, intravenous (iv), and sc single-dose pharmacokinetic data in beagle dogs. The resulting simulated TV-46000 PK profile in humans showed that the shape of the predicted risperidone and its active metabolite 9-OH-risperidone PK profiles was different from the observed one, thus suggesting that the TV-46000 release profile was species-dependent and cannot be directly extrapolated from dog to human. In conclusion, while level A IVIVC cannot be claimed, this work combining PBPK and IVIVC modeling represents an interesting alternative approach for complex injectable formulations where classical methods are not applicable.

The impact of metronidazole on pain persistence after fertility-sparing endometriosis surgery: METROFERT randomized study

Recent studies have shown that a disrupted microbiome is associated with endometriosis. Despite endometriosis affecting 1 in 10 reproductive-aged women, there is a lack of innovative and nonhormonal long-term effective treatments. Studies have reported an approximately 20% to 37.5% persistence of pain after fertility-sparing endometriosis surgery. Metronidazole has been shown to decrease inflammatory markers and the size of endometriosis lesions in animal studies. To determine if modulating the microbiome with oral metronidazole for 14days after fertility-sparing endometriosis surgery decreases pain persistence postoperatively. This was a randomized, multicenter, placebo-controlled, double-blind trial. Individuals 18 to 50years old were prospectively randomized to placebo vs oral metronidazole for 14days immediately after endometriosis fertility-sparing excision surgery. The primary outcome was binary, subjective pain persistence at 6weeks postoperatively. Secondary outcomes included quality of life, sexual function, and endometriosis-associated pain scores according to the Endometriosis Health Profile-5, Female Sexual Function Index, and a visual analog scale. One hundred fifty-two participants were approached from October 2020 to October 2023 to enroll in the study. Sixty-four participants were excluded either because they did not meet inclusion or exclusion criteria or because they declined to participate. Eighty-eight participants were randomized in a 1:1 ratio to receive either the oral placebo or metronidazole after endometriosis excision surgery; 18.2% of participants were lost to follow-up or discontinued treatment and this was not significantly different between the 2 arms, yielding a final cohort of 72 participants. Baseline demographics of the 2 study groups were similar. There was no statistically significant improvement in the primary outcome of binary subjective pain persistence between the metronidazole group compared to placebo (84% vs 88%, P=.74) at 6weeks postoperatively. Further, no significant differences between treatments were detected in the secondary outcomes. A postoperative 14-day regimen of oral metronidazole immediately after fertility-sparing endometriosis surgery was not associated with any significant differences between treatment groups in the persistence of endometriosis-related pain symptoms compared to placebo at 6weeks.

Ten years of maintenance treatment of severe melancholic depression in an adult woman including discontinuation experiences.

There are only few publications on long-term treatments for major depressive disorder (MDD) lasting 5 years or longer. Most clinical controlled trials lasted no longer than 2 years and some recent studies suggested an advantage of cognitive behavioral therapy (CBT) over antidepressants in relapse prevention of MDD. Exclusively outpatient "real world" treatment of severe melancholia, prospectively documented over 10 years with different serial treatment strategies, discontinuation phenomena and complications. Compared to CBT, agomelatine, mirtazapine, bupropion and high-dose milnacipran, high-dose venlafaxine (extended-release form, XR) was effective, even sustainably. Asymptomatic premature ventricular contractions (PVCs) were found at the beginning of the treatment of the MDD, which initially led to the discontinuation of high-dose venlafaxine (300 mg daily). Even the various treatment strategies mentioned above were unable to compensate for or prevent the subsequent severe deterioration in MDD (2 rebounds, 1 recurrence). Only the renewed use of high-dose venlafaxine was successful. PVC no longer occurred and the treatment was also well tolerated over the years, with venlafaxine serum levels at times exceeding 5 times the recommended upper therapeutic reference level (known bupropion-venlafaxine interaction, otherwise 2.5 to 3-fold increase with high-dose venlafaxine alone). During dose reduction or after gradual discontinuation of high-dose venlafaxine, rather mild withdrawal symptoms occurred, but as described above, also two severe rebounds and one severe recurrence happened. This long-term observation supports critical reflections on the discontinuation of successful long-term treatment with antidepressants in severe MDD, even if it should be under "the protection" of CBT. The PVC seemed to be more related to the duration of the severe major depressive episode than to the venlafaxine treatment itself. A particular prospective observation of this longitudinal case study is that relapses (in the sense of rebounds) during or after previous venlafaxine tapering seemed to herald the recurrence after complete recovery. Remarkably, neither relapses nor recurrence could be prevented by CBT. In this case, high-dose venlafaxine has a particular relapse-preventive (and "recurrence-preventive") effect with good long-term tolerability.

A 3-year follow-up study of outcomes associated with patterns of traditional acute and preventive migraine treatment: An administrative claims-based cohort study in the United States.

To describe treatment patterns and direct healthcare costs over 3 years following initiation of standard of care acute and preventive migraine medications in patients with migraine in the United States. There are limited data on long-term (>1 year) migraine treatments patterns and associated outcomes. This was a retrospective, observational cohort study using US claims data from the IBM® MarketScan® Research Database (January 2010-December 2017). Adults were included if they had a prescription claim for acute migraine treatments (AMT) or preventive migraine treatments (PMT) in the index period (January 2011-December 2014). The AMT cohort was categorized as persistent, cycled, or added-on subgroups; the PMT cohort was categorized PMT-persistent, switched without gaps, or cycled with gaps. Migraine-specific annual direct costs (2017 US$) across AMT and PMT cohort subgroups were summarized at baseline through 3 years from index (follow-up). During the index period, 20,778 and 42,259 patients initiated an AMT and a PMT, respectively. At the 3-year follow-up, migraine-specific direct costs were lower in the persistent subgroup relative to the non-persistent subgroups in both AMT (mean [SD]: $789 [$1741] vs. $2847 [$8149] in the added-on subgroup and $862 [$5426] for the cycled subgroup) and PMT cohorts (mean [SD]: $1817 [$5892] in the persistent subgroup vs. $4257 [$11,392] in the switched without gaps subgroup and $3269 [$18,540] in the cycled with gaps subgroup). Acute medication overuse was lower in the persistent subgroup (1025/6504 [27.2%]) vs. non-persistent subgroups (11,236/58,863 [32.2%] in cycled with gaps subgroup and 1431/6504 [39.4%] in the switched without gaps subgroup). Most patients used multiple acute (19,717/20,778 [94.9%]) or preventive (38,494/42,259 [91.1%]) pharmacological therapies over 3 years following treatment initiation. Gaps in preventive therapy were common; an average gap ranged from 85 to 211 days (~3-7 months). Migraine-specific annual healthcare costs and acute migraine medication overuse remained lowest among patients with persistent AMT and PMT versus non-persistent treatment. Study findings are limited to the US population. Future studies should compare costs and associated outcomes between newer preventive migraine medications in patients with migraine.

Emotions in search of words: Does alexithymia predict treatment outcome in chronic musculoskeletal pain?

Chronic pain, with its complex and multidimensional nature, poses significant challenges in identifying effective long-term treatments. There is growing scientific interest in how psychopathological and personality dimensions may influence the maintenance and development of chronic pain. This longitudinal study aimed to investigate whether alexithymia can predict the improvement of pain severity following a treatment-as-usual programme for chronic musculoskeletal pain over and above psychological cofactors (emotional distress, catastrophizing, and self-efficacy). A consecutive sample of 129 patients with diagnosed chronic musculoskeletal pain referred to two tertiary care centres was recruited and treated for 16weeks. Clinical pain, psychological distress, self-efficacy, catastrophizing, and alexithymia were assessed with validated self-report measures at the first medical visit (T0) and at 16-week follow-up (T1). Compared with non-responder patients (n=72, 55.8%), those who responded (i.e., reduction of >30% in pain severity; n=57, 44.2%) reported an overall improvement in psychological variables except alexithymia. Alexithymia showed relative stability between baseline and follow-up within the entire sample and remained a significant predictor of treatment outcome even when other predictive cofactors (i.e., pain interference, depressive symptoms, and catastrophizing) were considered simultaneously. Our results suggest that identifying patients with a co-occurrence between alexithymia, depressive symptoms, catastrophizing, and the stressful experience of chronic pain can be clinically relevant in pain prevention and intervention programs.

Nano-fenretinide demonstrates remarkable activity in acute promyeloid leukemia cells

Acute promyelocytic leukemia (APL) is characterized by rearrangements of the retinoic acid receptor, RARα, which makes all-trans retinoic acid (ATRA) highly effective in the treatment of this disease, inducing promyelocytes differentiation. Current therapy, based on ATRA in combination with arsenic trioxide, with or without chemotherapy, provides high rates of event-free survival and overall survival. However, a decline in the drug activity, due to increased ATRA metabolism and RARα mutations, is often observed over long-term treatments. Furthermore, dedifferentiation can occur providing relapse of the disease. In this study we evaluated fenretinide, a semisynthetic ATRA derivative, encapsulated in nanomicelles (nano-fenretinide) as an alternative treatment to ATRA in APL. Nano-fenretinide was prepared by fenretinide encapsulation in a self-assembling phospholipid mixture. Physico-chemical characterization was carried out by dinamic light scattering and spectrophotometry. The biological activity was evaluated by MTT assay, flow cytometry and confocal laser-scanning fluorescence microscopy. Nano-fenretinide induced apoptosis in acute promyelocytic leukemia cells (HL60) by an early increase of reactive oxygen species and a mitochondrial potential decrease. The fenretinide concentration that induced 90–100% decrease in cell viability was about 2.0 µM at 24 h, a concentration easily achievable in vivo when nano-fenretinide is administered by oral or intravenous route, as demonstrated in previous studies. Nano-fenretinide was effective, albeit at slightly higher concentrations, also in doxorubicin-resistant HL60 cells, while a comparison with TK6 lymphoblasts indicated a lack of toxicity on normal cells. The results indicate that nano-fenretinide can be considered an alternative therapy to ATRA in acute promyelocytic leukemia when decreased efficacy, resistance or recurrence of disease emerge after protracted treatments with ATRA.

Effects of Straw Addition on N2O and CO2 Emissions from Red Soil Subjected to Different Long-Term Fertilization

Straw return, as an important measure for soil fertility improvement in farmland, significantly affects the emissions of greenhouse gases N2O and CO2. Thus, the collected soil samples from five long-term (30-year) fertilization treatments (no fertilization, CK; recommended chemical fertilizer, F; 200 % of recommended chemical fertilizer, 2F; pig manure, M; and chemical fertilizer combined with pig manure, FM) were amended with and without straw and incubated under constant temperature and humidity conditions (25 ℃ and 65 % maximum field water holding capacity) for 20 days so as to investigate the key factors influencing N2O and CO2 emissions in response to straw addition in long-term fertilization treatments. The results showed that fertilization significantly increased N2O emissions. Compared to those under the unfertilized treatment[(22.05 ±2.09) μg·kg-1, calculated as nitrogen, the same as below], cumulative N2O emissions from the chemical fertilizer treatments significantly increased by 119 %-195 %[(48.38 ±20.81) μg·kg-1 and (65.13 ±12.55) μg·kg-1 from the F and 2F treatments, respectively], and those from the manure treatments increased by 275 %-399 %[(82.72 ±12.73) μg·kg-1 and (1 101.99 ±425.71) μg·kg-1 from the M and FM treatments, respectively]. Soil NO3--N, DOC, and DTN were the main factors influencing N2O emissions from fertilized treatments in the absence of straw addition. Straw addition significantly increased cumulative N2O emissions by 345 % and 247 % in the 2F and M treatments, respectively, compared to those in the corresponding fertilized treatments without straw addition, with no significant effect on N2O emissions in the CK, F, and FM treatments. Straw addition increased DOC content and microbial activity and decreased soil NO3--N and DTN contents, thereby increasing N2O emissions. Fertilization also significantly increased CO2 emissions. Compared to those from the unfertilized treatment, cumulative CO2 emissions from the manure treatments significantly increased by 120 %-130 %[(122.11 ±4.3) mg·kg-1 (calculated as carbon, the same as below) and (116.47 ±4.55) mg·kg-1 from the M and FM treatments, respectively], and those in the 2F treatment increased by 28 %[(65.13 ±12.55) mg·kg-1]. In the absence of straw addition, soil MBC, DOC, and DTN were the main factors influencing CO2 emissions. Compared to those in the treatments without straw addition, straw addition significantly increased cumulative CO2 emissions by 660 %-1132 % among fertilization treatments, due to increased DOC and MBC contents and enhanced microbial activity. In conclusion, straw addition significantly increased N2O and CO2 emissions through increased soil DTN consumption and DOC content among fertilization treatments. In soils treated with manure amendment, straw return should be rationally considered for the purpose of balancing the comprehensive trade-offs between fertility improvement and greenhouse gas emissions.

Identification and analysis of short-term and long-term salt-associated lncRNAs in the leaf of Avicennia marina

As a highly salt-resistant mangrove, Avicennia marina can thrive in the hypersaline water. The leaves of Avicennia marina play a crucial role in salinity stress adaptability by secreting salt. Although the functions of long non-coding RNAs (lncRNAs) in leaves remain unknown, they have emerged as regulators in leaf development, aging and salt response. In this study, we employed transcriptomic data of both short-term and long-term salt treated leaves to identify salt-associated lncRNAs of leaf tissue. As a result, 687 short-term and 797 long-term salt-associated lncRNAs were identified. Notably, both short-term and long-term salt-associated lncRNAs exhibited slightly longer lengths and larger exons, but smaller introns compared with salt-non-associated lncRNAs. Furthermore, salt-associated lncRNAs also displayed higher tissue-specificity than salt-non-associated lncRNAs. Most of the salt-associated lncRNAs were common to short- and long-term salt treatments. And about one fifth of the downregulated salt-associated lncRNAs identified both in two terms were leaf tissue-specific lncRNAs. Besides, these leaf-specific lncRNAs were found to be involved in the oxidation–reduction and photosynthesis processes, as well as several metabolic processes, suggesting the noticeable functions of salt-associated lncRNAs in regulating salt responses of Avicennia marina leaves.

Discontinuation of Nucleos(t)ide Analogues in HBeAg Negative Chronic Hepatitis B Patients: Risks and Benefits.

Chronic hepatitis B (CHB) remains a major threat to global public health, affecting 296 million people worldwide. Although there is no curative treatment for CHB today, the virus can be effectively controlled with current antiviral treatment strategies. Since HBsAg loss can rarely (1%) be achieved with current nucleos(t)ide analogues (NA) options, lifelong treatment is usually required in HBeAg-negative patients. In recent years, guidelines have stated that long-term NA treatments can be discontinued for HBeAg-negative patients without achieving HBsAg loss. There is no general consensus on how discontinuation of NA can be included in the treatment approach. This review aimed to evaluate the current literature regarding the discontinuation of NA treatment in HBeAg-negative patients. Patients with HBeAg-negative CHB who have a higher chance of response after discontinuation of NA therapy can be defined as non-cirrhotic patients who have low HBsAg, HBcrAg, and HBV RNA levels at the discontinuation of treatment and accept close follow-up. The management of relapses that develop after NA discontinuation in patients is also unclear. The agent used in NA treatment itself may also affect the pattern of relapse development. Relapse after NA treatment occurs significantly slower and less frequently with entecavir compared to other regimens, including tenofovir dipivoxil. Prospective studies are needed in order to maintain the chance of HBsAg clearance in case of exacerbation and to treat acute exacerbations that can be fatal in a timely manner. Algorithms to be developed for use after discontinuation of NA treatment will help the clinician manage the patient safely.

Understanding the dynamics of TKI-induced changes in the tumor immune microenvironment for improved therapeutic effect

BackgroundThe dynamic interplay between tyrosine kinase inhibitors (TKIs) and the tumor immune microenvironment (TME) plays a crucial role in the therapeutic trajectory of non-small cell lung cancer (NSCLC). Understanding the...

Microbiome Taxonomic and Functional Differences in C3H/HeJ Mice Fed a Long-Term High-Fat Diet with Beef Protein ± Ammonium Hydroxide Supplementation.

Studies have suggested that alkalinized foods may reduce the effects of the acidogenic Western diet in promoting obesity, metabolic syndrome, type 2 diabetes, cancer, and coronary heart disease. Indeed, a recent study in mice fed a high-fat diet containing dietary beef supplemented with ammonium hydroxide showed improvement in a suite of metabolic outcomes. However, the effects of dietary protein ammonium supplementation on the microbiome remain unknown. In this study, the effects of ammonium supplementation on beef protein towards microbiome taxa and function in a high-fat diet were analyzed. Fecal microbiomes were characterized using a shotgun metagenomic approach for 16-month-old male and female mice after long-term diet treatments. The results for ammoniated diets showed that several bacteria known to be associated with health benefits increased significantly, including Romboutsia, Oscillospiraceae, and Lactococcus cremoris. The beneficial mucin-degrader Akkermansia was especially abundant, with a high prevalence (~86%) in females. Concurrently, the phyla Actinomycetota (Actinobacteria) and Bacteroidota (Bacteroidetes) were significantly reduced. While sex was a confounding factor affecting microbiome responses to ammonium supplementation in dietary protein, it is worth noting that several putatively beneficial microbiome functions increased with ammonium supplementation, such as glycine betaine transport, xenobiotic detoxification, enhanced defense, and others. Conversely, many disease-associated microbiome functions reduced. Importantly, modifying protein pH alone via ammonium supplementation induced beneficial microbiota changes. Taken together, these results suggest that ammonium-supplemented proteins may mediate some negative microbiome-associated effects of high-fat/Western diets.

Effects of polyurethane microplastics combined with cadmium on maize growth and cadmium accumulation under different long-term fertilisation histories

Agricultural production uses different types of fertilisation treatments, typically employing the combined application of organic fertiliser (OF) or organic–inorganic fertiliser (OIF) to improve soil quality. When coupled with cadmium (Cd), microplastics (MPs) affect plant growth and Cd accumulation in soils treated with different fertilisers. This study systematically examined the effects of polyurethane (PU) MPs coupled with Cd on the growth characteristics, root metabolite characteristics, rhizosphere bacterial community structure, and Cd bioavailability of maize under different long-term fertilisation treatments and soil types (red/cinnamon soil). The combined effects of PU MPs and Cd on maize growth differed across fertilisation treatments. Under OF, maize plants accumulated more Cd than under OIF. The accumulation of Cd in maize plants in red soil was twice that in cinnamon soil. Under OF, PU MPs promoted Cd activation by decreasing the soil pH, while root metabolites promoted Cd adsorption sites by synthesising specific amino acids, degrading aromatic compounds, and synthesising pantothenic acid and coenzyme A. Under OF, PU MPs can lower the soil pH to promote the activation of cadmium, while root metabolites promote root growth and increase cadmium adsorption sites by synthesizing specific amino acids, degrading aromatic compounds, and synthesizing pantothenic acid and coenzyme A, hereby promoting root Cd absorption. Under OIF, PU MPs act by influencing the biosynthesis of amino acids in root metabolites, enriching energy metabolism pathways, promoting the transport and translocation of mineral nutrients, thereby amplifying the "toxic effects" of Cd. This study provides new insights into the risk assessment of PU MPs and Cd coupling under different fertilisation treatments, and suggests that the prevention and control of combined PU MPs and Cd pollution in red soil under OF treatment should receive more attention in the future.