Chain Synthesis Research Articles

IgG and kappa free light chain CSF/serum indices: evaluating intrathecal immunoglobulin production in HIV infection in comparison with multiple sclerosis.

To study intrathecal kappa free light chain (KFLC) synthesis in people living with HIV (PLWH) in comparison with multiple sclerosis (MS). Cross-sectional analysis including 56 untreated and 150 well treated PLWH, and compared with 58 controls, and 223 MS patients. Elevated serum/cerebrospinal fluid (CSF) IgG and KFLC indices were observed in untreated PLWH. Seventy percent of untreated PLWH had KFLC index above 6.1, a threshold associated with clinically isolated syndrome/MS diagnosis. No association was found between KFCL index and CSF markers of neuronal injury in either PLWH or MS patients. HIV-related immune system dysfunction is often associated with an elevated KFLC index akin to those observed in MS. HIV infection should be considered as a differential diagnosis for patients presenting with neurological symptoms and increased intrathecal immunoglobulin synthesis.

A synthesis method for epicyclic chains based on new topological model and similarity

The structural design is a prerequisite for the creation of mechanical equipment. This study focuses on the structural synthesis of epicyclic chains (ECs), and proposes a new topological model and synthesis method of ECs to address the existing research problems (i.e. synthesis dependence on multiple graphic transformations and the generation of pseudo-isomorphism). First, the structural characteristics of ECs are analyzed to explore the relation between their axles, gears, and planet carriers, and the corresponding topological model and the adjacency matrix expression of ECs are provided. Then, the topological elements corresponding to the axles, gears, and gear pairs are added sequentially to the topological graph corresponding to the planet carriers, and the constraints are established based on similarity to inhibit the generation of isomorphism. Finally, all the databases of feasible ECs are obtained through gear loop discrimination. All processes are carried out with computer assistance. The synthesis results of the ECs with 1–3 degrees of freedom and up to 10 components are presented. The logic of this paper is to simplify (or optimize) the synthesis process to improve efficiency of structural synthesis, which will break through the threshold of computing power and provide more possibilities for the design of mechanical equipment.

Synthesis and characterization of carbon nanopearl chains on Co-Coated silicon substrate by CVD method

Carbon nanopearl chains (CNPCs) consisted of carbon nanospheres and carbon nanofibers were prepared by chemical vapor deposition (CVD) method using benzene as the carbon source and Co particles on Si-substrate as the catalyst. The characterized results confirmed that the carbon nanospheres with a diameter between 80 nm and 300 nm have solid structure and wavy graphite layered surface, while the carbon nanofibers (diameter: 16 nm) showed amorphous structure and excellent flexibility. Therefore, these synthesized CNPCs can be potentially applied as the reinforcing matrix. Moreover, the growth mechanism of CNPCs has also been proposed by investigating the effects of Co catalyst, thiophene promoter and gas-flow during the growth process.

MT-TN mutations lead to progressive mitochondrial encephalopathy and promotes mitophagy

Mitochondrial encephalopathy is a neurological disorder caused by impaired mitochondrial function and energy production. One of the genetic causes of this condition is the mutation of MT-TN, a gene that encodes the mitochondrial transfer RNA (tRNA) for asparagine. MT-TN mutations affect the stability and structure of the tRNA, resulting in reduced protein synthesis and complex enzymatic deficiency of the mitochondrial respiratory chain. Our patient cohort manifests with epileptic encephalopathy, ataxia, hypotonia, and bilateral basal ganglia calcification, which differs from previously reported cases. MT-TN mutation deficiency leads to decreased basal and maximal oxygen consumption rates, disrupted spare respiratory capacity, declined mitochondrial membrane potential, and impaired ATP production. Moreover, MT-TN mutations promote mitophagy, a process of selective degradation of damaged mitochondria by autophagy. Excessive mitophagy further leads to mitochondrial biogensis as a compensatory mechanism. In this study, we provided evidence of pathogenicity for two MT-TN mutations, m.5688 T > C and m.G5691A, explored the molecular mechanisms, and summarized the clinical manifestations of MT-TN mutations. Our study expanded the genotype and phenotypic spectrum and provided new insight into mt-tRNA (Asn)-associated mitochondrial encephalopathy.

Isoliquiritin can cause mitochondrial dysfunction and regulate Nrf2 to affect the development of mouse oocytes

IsoliQuirtigenin (ILG) has been widely studied in somatic cells and tissues, but less in reproductive development. It is a kind of widely used food additive. In this study, it was found that ILG could significantly increase the levels of ROS,GSH and MMP in mouse oocytes (P < 0.01). In order to explore the cause of this phenomenon, it was found that the abnormal distribution of mitochondria and ATP synthesis levels were significantly increased (P < 0.05). At this time, we made a reasonable hypothesis that ILG affected mitochondrial function. In subsequent studies, it was found that the endogenous ROS accumulation level in mitochondria was significantly increased. After continuous RT-PCR screening, it was found that the expression of Nrf2 was significantly inhibited (P < 0.01). Its upstream and downstream FOXO3 GPX1, CAT, SOD2, SIRT1 gene also appear different degree of significant change (P < 0.05), in which the lower expression of NADP + (P < 0.05) illustrates the mitochondrial ATP synthesis electronic chain were suppressed, it also has the reason, By inhibiting electron chain and ATP synthesis, ILG leads to oocyte apoptosis and initiation of autophagy, reducing oocyte and its subsequent developmental potential.

Rhodotorula mucilaginosa survives under extreme conditions by using and controlling both, a branched respiratory chain and carotenoid synthesis

Rhodotorula mucilaginosa survives under extreme conditions by using and controlling both, a branched respiratory chain and carotenoid synthesis

A study conducted in a tertiary care hospital to assess the cardiac function in paediatric beta thalassemia major patients and correlation with serum ferritin levels which are indicative of chelation status of the patients

Background: Thalassemia is one of the common inherited blood disorders and Beta Thalassemia Major is a homozygous form of deficiency of beta globin chain synthesis causing severe transfusion-dependent anemia, manifesting between 6 and 24 months of life. Objectives: The objective of the study is to study the pattern of cardiac function in children and adolescents with beta-thalassemia major by 2D Echocardiography and its correlation with serum ferritin levels. Methods: Fifty subjects diagnosed with Beta Thalassemia Major, after applying the inclusion and exclusion criteria were included in Group 1, and 50 age and gender-matched subjects without Beta Thalassemia Major were included in Group 2. Serum ferritin level was measured using Cobas 6000 analyzer. Echocardiography was done with the following parameters: Posterior wall thickness-diastolic (PWT-D), posterior wall thickness- systolic (PWT-S), left ventricular internal diameter-diastole (LVID-D), left ventricular internal diameter-systole (LVID-S), septal thickness and tricuspid regurgitation (TR) velocity. Results: Among the 50 study population, 28 children belonged to the age group 5–10 years (56%) and 22 children belonged to the age group 10–15 years (44%). Among the cardiac parameters, The PWT-D, PWT-S, LVID-D, LVID-S, TR velocity, and septal thickness values were higher in the cases group compared to the control group with p values suggesting strong significance. The ejection fraction in the cases was lower than the control group with a strongly significant p-value. Conclusion: Children with thalassemia have impaired cardiac function and the degree of dysfunction is correlated to the serum ferritin levels. Regular transfusion and adequate chelation are essential to decrease morbidity and mortality.

A Closed-Loop Recyclable Low-Density Polyethylene.

Low-density polyethylene (LDPE) is one of the most important plastics, which is produced unfortunately under extreme conditions. In addition, it consists of robust aliphatic C─C bonds which are challenging to cleave for plastic recycling. A low-pressure and -temperature (pethylene=2bara, T=70°C) macromonomer-based synthesis of long chain branched polyethylene is reported. The introduction of recycle points permits the polymerization (grafting to) of the macromonomers to form the long chain branched polyethylene and its depolymerization (branch cleavage). Coordinative chain transfer polymerization employing ethylene and co-monomers is used for the synthesis of the macromonomers, permitting a high flexibility of their precise structure and efficient synthesis. The long chain branched polyethylene material matches key properties of low-density polyethylene.

On-surface synthesis and characterization of polyynic carbon chains.

Carbyne, an elusive sp-hybridized linear carbon allotrope, has fascinated chemists and physicists for decades. Due to its high chemical reactivity and extreme instability, carbyne was much less explored in contrast to the sp2-hybridized carbon allotropes such as graphene. Herein, we report the on-surface synthesis of polyynic carbon chains by demetallization of organometallic polyynes on the Au(111) surface; the longest one observed consists of ∼60 alkyne units (120 carbon atoms). The polyynic structure of carbon chains with alternating triple and single bonds was unambiguously revealed by bond-resolved atomic force microscopy. Moreover, an atomically precise polyyne, C14, was successfully produced via tip-induced dehalogenation and ring-opening of the decachloroanthracene molecule (C14Cl10) on a bilayer NaCl/Au(111) surface at 4.7K, and a band gap of 5.8eV was measured by scanning tunnelling spectroscopy, in a good agreement with the theoretical HOMO-LUMO gap (5.48eV).

Analysis Of The Cost Effectiveness Of Oral Iron Cleaning Drugs Between Deferipron And Deferasiroks In Patients With Thalasemia Major At Bhayangkara Kindergarten Hospital. Ii Setukpa Lemdiklat Polri

Thalassemia is a blood disorder characterized by reduced or absent synthesis of globin chains, particularly thalassemia major, imposes significant financial burdens due to the lifelong need for blood transfusions and iron chelation drugs. This research aims to assess the cost and efficacy of oral iron chelators, specifically deferasirox and deferiprone, in treating thalassemia major patients at Setukpa Lemdiklat Polri Tk—II Hospital in 2023. The data were retrospectively gathered through total sampling from patients' medical records and the hospital information system. The findings indicate that the average total treatment cost for thalassemia major patients using deferasirox (IDR 52,969,775,-) is higher than deferiprone (IDR 49,407,613,-). Deferasirox exhibits greater effectiveness (1,364 ng/mL) than deferiprone (1,210 ng/mL). The cost-effectiveness ratio of deferasirox (IDR 38,834,-) is lower than that of deferiprone (IDR 40,833,-). Transitioning from deferiprone to deferasirox incurs an additional IDR 23,130 per unit cost. The average cost-effectiveness ratio suggests that deferasirox is more economically efficient than deferiprone.thalassemia major

Enhanced NF-κB activation via HIV-1 Tat-TRAF6 cross-talk.

The Tat proteins of HIV-1 and simian immunodeficiency virus (SIV) are essential for activating viral transcription. In addition, Tat stimulates nuclear factor κB (NF-κB) signaling pathways to regulate viral gene expression although its molecular mechanism is unclear. Here, we report that Tat directly activates NF-κB through the interaction with TRAF6, which is an essential upstream signaling molecule of the canonical NF-κB pathway. This interaction increases TRAF6 oligomerization and auto-ubiquitination, as well as the synthesis of K63-linked polyubiquitin chains to further activate the NF-κB pathway and HIV-1 transcription. Moreover, ectopic expression of TRAF6 significantly activates HIV-1 transcription, whereas TRAF6 knockdown inhibits transcription. Furthermore, Tat-mediated activation of NF-κB through TRAF6 is conserved among HIV-1, HIV-2, and SIV isolates. Our study uncovers yet another mechanism by which HIV-1 subverts host transcriptional pathways to enhance its own transcription.

Exploring the relationship between thalassemia and bone health: A clinicopathological analysis

Objectives: To study the bone mineral density in patients with thalassemia. Thalassemia is a genetic disorder characterized by reduced synthesis of the globin chain, leading to decreased hemoglobin levels. Blood transfusion therapy is the primary treatment, but it can cause iron overload and other factors that increase the risk of low bone mineral density. Despite this, there is limited research on thalassemia patients in India, particularly in the North Eastern region, with a focus on bone mineral density. Material and Methods: We conducted a hospital-based case-control study in the Department of Medicine at Assam Medical College and Hospital, Dibrugarh, from June 1, 2020, to May 31, 2021. We have collected data from 51 cases and 51 healthy controls and analyzed it (SPSS for Windows, version 21.0 Chicago, SPSS Inc.) and Microsoft Excel 2010. Bone mineral density was measured by Dual-Energy X-ray Absorptiometry (DEXA) (Lunar Prodigy Advance DEXA (GE Healthcare, Madison, WI, USA). Results: Our study also showed that thalassemia patients had a 3.775 times higher risk of low bone mineral density at the lumbar vertebra and a 4.0421 times higher risk at the femur neck than the normal healthy population. The mean BMD at the lumbar spine and femur neck were lower for cases than controls, with the difference at the femoral neck being statistically significant. Conclusion: Our study highlights that more than half of thalassemia patients have low bone mineral density, with the femoral neck and lumbar neck being more affected than normal age and sex-matched controls. These findings underscore the importance of monitoring bone health in thalassemia patients and implementing appropriate interventions to prevent or manage low bone mineral density.

Identification of a Novel Variant c.163delG in HBB Gene Resulting in a Beta Null Phenotype in a Proband with Thalassemia Intermedia

A 21-year-old patient presented with a previous medical history of pallor, mild icterus, increased fatigue, low hemoglobin, and abnormal hemoglobin variant analysis with more than 70 transfusions. He was referred for genetic analysis to identify the pathogenic variations in the β-globin gene. Sanger’s sequencing of the proband and his family revealed the presence of a novel frame shift variant HBB:c.163delG in a compound heterozygous state with hemoglobin E (HbE) (HBB:c.79G > A) variant. The father and the sibling of the patient were found to be normal for the HBB gene. Mother was found to be heterozygous for HbE (HBB:c.79G > A) variant. In silico analysis by Mutalyzer predicted that c.163delG variant generated a premature stop codon after seven codons, leading to a truncated protein. FoldX protein stability analysis showed a positive ΔΔG value of 45.27 kcal/mol suggesting a decrease in protein stability. HBB:c.79G > A is a known variant coding for HbE variant, which results in the reduced synthesis of β-globin chain and shows mild thalassemia. Combined effect of HBB:c.163delG and HBB:c.79G > A variants in the proband might have led to the reduced synthesis of β-globin chains resulting in a thalassemia intermedia type of clinical manifestation.

ПОПЕРЕДЖЕННЯ ТА УНИКНЕННЯ РИЗИКІВ У ГЛОБАЛЬНИХ ЛАНЦЮГАХ ПОСТАЧАННЯ

In modern market conditions, it is important to correctly assess and manage risks in order to increase the competitiveness and economic stability of enterprises. This article examines the main factors that influence the formation of risks in global supply chains. Controllable and uncontrollable factors, external and internal, are defined. It was established that factors of uncertainty and risks must be taken into account at the stage of both the structural and functional synthesis of supply chains and the implementation of plans. This significantly complicates the processes of structural formation and planning, increases the requirements for flexibility, efficiency and stability of supply chains, the development of mechanisms for coordinated actions of companies in regular and non-regular situations. Although various concepts, models and information systems have been developed over the past 30 years to reduce uncertainty and risk in supply chains, in practice and in theory, this topic is becoming increasingly popular. This article presents the author’s view on the issue of uncertainty and risk in supply chains. Methods for reducing risks in supply chains include: introducing redundancy in structures(expanding the range of products, introducing temporary buffers, safety stocks, additional warehouses, capacity reserves, etc.); improving coordination and information exchange to improve the quality, timeliness and availability of demand forecasts for all supply chain participants; introducing a system for monitoring and regulating supply chains in the event of violations and deviations from the plan; unification of supply chain management elements (endowing various decision-making areas with a variety of management functions so that, for example, if it is impossible to perform a management function in area A, this function can be performed in area B; design of transport systems with alternative delivery routes; development of inter-organizational plans for actions in conditions of disruption of planned processes and elimination of consequences of disruptions in supply chains (contingency plans); standardization of production processes to increase flexibility of capacity use; documentation of disruptions and personnel training. The article emphasizes the importance of applying preventive measures in the system of risk management in global supply chains, suggests strategies for preventing and avoiding risks.

Synthesis and photoluminescence properties of polymer chains based on pre-designed heterometallic Al4Ln4 molecular rings.

Presented herein is a series of chain compounds based on pre-designed heterometallic aluminum-lanthanide (Al-Ln) Al4Ln4 molecular rings. Their photoluminescence quantum yield (PLQY) with Eu3+ (30.41%) and Tb3+ (41.44%) is at a high level among the clusters containing four Ln ions. This study significantly extends the family of Al-Ln heterometallic clusters and demonstrates the synergistic effect of heterometallic ions in enhancing their properties.

Nature-derived Alkaloids as a Promising Bioactive Compound in Drug Discovery to Meet Global Leishmania Needs

Background: Natural products have been important resources for potential drug development. Among the many classes of natural products, alkaloids have the most therapeutic applications. Treatment of leishmaniasis by chemical drugs remains a challenge because of toxic side effects, limited efficacy, and drug resistance. This review focuses to embrace all researches on leishmanicidal alkaloids over a specific range of time, with special consideration the molecular mechanism of action, and structure-related activity. Methods: All publications (in English) from Web of Science, PubMed, Science Direct, Scopus, and Google Scholar from 2000-2021 using a variety of keywords such as natural alkaloids, herbal alkaloids, marine alkaloids along with leishmaniasis were included in the present study. In this summary, the focus is mainly on natural alkaloids of plant, mineral, marine origin, etc., which have empirically demonstrated the antileishmanial effect. Results: Fourteen categories of alkaloids with anti-leishmaniasis activity were extracted from the articles. The highest number of alkaloids belonged to isoquinoline, indole, and quinoline alkaloids (21.78%, 20.67%, and 16.48% respectively). This review indicated that the mentioned alkaloids are able to inhibit the proliferation of parasites, the respiratory chain and protein synthesis, arrest the cell cycle, disrupt the mitochondrial membrane integrity, inhibit leishmanial topoisomerase, induce mitochondrial dysfunction, and changes in the parasite morphology. Discussion: The present study highlighted antileishmanial alkaloids that are active against different species of Leishmania in vitro and some of them are also active in visceral and cutaneous leishmaniasis models. However, more clinical studies are needed to clarify the anti-leishmanial activity of alkaloids against leishmania in detail. Conclusion: Among the reported compounds, two main classes of alkaloids including isoquinoline and indole alkaloids cover a wider range of anti-parasitic compounds, and structure-activity relationships (SAR) studies of these molecular skeletons may be good lead compounds and afford the structural clues to develop novel medicines with more selective therapeutic profiles.

Gender Disparities in Psychological Disturbances and Quality of Life Among Adolescent and Adult Patients with Thalassemia: A Review.

Thalassemia is a chronic disease caused by impaired globin chain synthesis, leading to ineffective erythropoiesis, hemolysis, and chronic anemia. The treatment of patients with thalassemia, including blood transfusion combined with chelation therapy has progressed and improved their survival and prognosis. However, thalassemia-related psychological problems and impaired health-related quality of life (QoL) challenges still exist. Gender is one of the factors that has been suggested, to contribute to the disparities in psychological outcomes. This review article examined the evidence for gender differences in psychological disturbances and QoL in adolescent and adult patients with thalassemia. A non-systematic search of the literature was conducted in PubMed and Google Scholar for English full-text available from 2013 to 2023. We identified 23 studies with a sample size ≥ 100 that examined gender disparities in anxiety, depression, and QoL in adolescent and adult patients with thalassemia (mean prevalence of female = 53.1%; mean age = 28 years). Our review shows that there are gender disparities in psychological distress and QoL in adolescent and adult patients with thalassemia. Statistically significant gender differences were demonstrated in 62% of the psychological and QoL outcomes from 16 studies. Female patients had a higher prevalence of anxiety, depression, and poorer QoL in some studies. However, further studies with sufficient power and design are necessary to confirm the existence of gender disparities in psychological disturbances and QoL outcomes.

ADP-Hep-Induced Liquid Phase Condensation of TIFA-TRAF6 Activates ALPK1/TIFA-Dependent Innate Immune Responses.

The ALPK1 (alpha-kinase 1)-TIFA (TRAF-interacting protein with fork head-associated domain)-TRAF6 signaling pathway plays a pivotal role in regulating inflammatory processes, with TIFA and TRAF6 serving as key molecules in this cascade. Despite its significance, the functional mechanism of TIFA-TRAF6 remains incompletely understood. In this study, we unveil that TIFA undergoes liquid-liquid phase separation (LLPS) induced by ALPK1 in response to adenosine diphosphate (ADP)-β-D-manno-heptose (ADP-Hep) recognition. The phase separation of TIFA is primarily driven by ALPK1, the pT9-FHA domain, and the intrinsically disordered region segment. Simultaneously, TRAF6 exhibits phase separation during ADP-Hep-induced inflammation, a phenomenon observed consistently across various inflammatory signal pathways. Moreover, TRAF6 is recruited within the TIFA condensates, facilitating lysine (K) 63-linked polyubiquitin chain synthesis. The subsequent recruitment, enrichment, and activation of downstream effectors within these condensates contribute to robust inflammatory signal transduction. Utilizing a novel chemical probe (compound 22), our analysis demonstrates that the activation of the ALPK1-TIFA-TRAF6 signaling pathway in response to small molecules necessitates the phase separation of TIFA. In summary, our findings reveal TIFA as a sensor for upstream signals, initiating the LLPS of itself and downstream proteins. This process results in the formation of membraneless condensates within the ALPK1-TIFA-TRAF6 pathway, suggesting potential applications in therapeutic biotechnology development.

Effects of vitamin D supplementation (oily form) in patients with thalassemia

Background. Thalassemia is congenital disease case by mutation effect to synthesis of beta globin chain of hemoglobin result in combination of metabolic and endocrine disorder. Bone disease is a not rare complication in thalassemia due to malabsorption of calcium, the secondary chronic renal disorder with low vitamin D (VD), as well as many endocrine risk factors. Aim. Evaluation of vitamin D treatment (oily form) in patients with thalassemia. Method. Post Marketing Surveillance (PMS) in 26 patients with Thalassemia in Ibn Al-Atheer Hospital. All patient take vitamin D oral vial oily form with dose 50000 IU, this PMS continued in 4 weeks, every week the patient take one vial. The Parameter for the level of VD. Result. The total number of patients was 26; mean age was 13.5 years, between 3-41 years, with 53.8% were males and 46.2% were females. mean serum level of vitamin D was statically significantly very lower in thalassemia patients than in than normal level; (89%) of cases had deficient VD (≤ 20 ng/ml), (7%) of cases had insufficient vitamin D (21–29 ng/ml), and (4%) of cases had deficient VD optimal vitamin D (more than 30 ng/ml), our study showed that 4 weeks of VD supplementation significantly increased the serum level of VD. Conclusion. VD (Oily based oral vial) “High D” significantly raise the VD level in serum in majority of thalassemia patients, the result was sustained regardless of age, gender and existence of other comorbidities.

Enzymatic Modification of Starch Using Recombinant Genes from Sorghum in Escherichia coli: Insights and Potential Applications.

SBEIIb (Sobic.004G163700), SSSIIa (Sobic.010G093400), and GBSSI (Sobic.010G022600) genes that regulate starch synthesis in sorghum endosperm were transferred into Escherichia coli by transgenic technology. SBEIIb, SSSIIa, and GBSSI enzymes were separated and purified through a Ni column and analyzed by electrophoresis with molecular weights and activities of 91.57 84.57, and 66.89 kDa and 551 and 700 and 587 U/μL, respectively. Furthermore, they were applied to starch modification, yielding interesting findings: the A chain content increased from 25.79 to 89.55% for SBEIIb-treated waxy starch, while SSSIIa extended the A chain to form DPs of the B chain, with A chain content decreasing from 89.55 to 37.01%, whereas GBSSI was explicitly involved in the synthesis of B1 chain, with its content increasing from 9.59 to 48.45%. Modified starch was obtained, which could be accurately applied in various industries. For instance, we prepared a sample (containing 89.6% A chain content) with excellent antiaging and antidigestion properties through SBEIIb modification. Moreover, higher RS3 (34.25%) and SDS contents (15.75%) of starch were obtained through the joint modification of SBEIIb and SSSIIa. These findings provide valuable insights for developing sorghum starch synthesis-related enzymes and offer opportunities for improving starch properties through enzymatic approaches.