High Response Research Articles

Zuberitamab, an innovative anti-CD20 monoclonal antibody, for patients with primary immune thrombocytopenia in China: a randomized, double-blind, placebo-controlled, phase 2 study

Primary immune thrombocytopenia (ITP) is an autoimmune disease, and rituximab (RTX) induces long-term effect as second-line treatments. Zuberitamab is an innovative anti-CD20 monoclonal antibody, which was first developed in China and launched in diffuse large B lymphoma. This study aimed to investigate the safety, efficacy, and anticipated therapeutic dose of zuberitamab in Chinese ITP patients. This randomised, double-blind, placebo-controlled, phase 2 study was conducted at 26 hospitals in China. Eligible patients were aged 18-70 years, had primary immune thrombocytopenia for more than 6 months, and did not respond or relapsed after previous treatment and had a pre-treatment platelet count of <30×109/L. Patients randomly received zuberitamab in a dose escalation (100/300/600mg) or placebo once-weekly for 4 weeks and followed up to 24 weeks. The primary endpoint is the proportion of patients with a platelet count ≥50×109/L at week 8. Secondary endpoints include the proportion of patients with platelet counts ≥50×109/L or ≥100×109/L at least once within week 12/24, the proportion of patients experiencing platelets increased twice more than baseline as well as ≥30×109/L at least once during the treatment. Adverse events, pharmacokinetic, B cell depletion and immunogenicity were also assessed. This study is registered with https://www.chictr.org.cn/as ChiCTR2100050513. From October 2021 to March 2023, 50 patients were screened for eligibility, of whom 32 patients were enrolled and randomly assigned to placebo (n=4), zuberitamab 100mg (n=10), 300mg (n=8) and 600mg (n=10) groups. The primary endpoint (PLT ≥50×109/L at week 8) was achieved by 40% of patients in the 100mg group, while none in the other groups. Within 12 weeks, the proportions of patients in each treatment group achieving at least one instance of platelet count ≥50×109/L or ≥100×109/L or an increase twice more than baseline as well as ≥30×109/L were (70%, 38%, 50%), (60%, 13%, 30%), and (80%, 50%, 70%) in zuberitamab 100/300/600mg groups, respectively. By week 24, the proportions of patients achieving these secondary endpoints remained relatively stable or showed a mild increase of around 10%. The anticipated therapeutic dose of zuberitamab was 100mg. The plasma concentration of zuberitamab showed an increasing trend with dose (100mg-600mg) and linear pharmacokinetic behavior. CD19+ B cells and CD20+ B lymphocytes rapidly declined to 0% within one week and consistently maintained reduced levels throughout the entire treatment phase in three groups. Adverse events occurred in all patients with most of them were mild to moderate, no severe infections occurred. A slight decrease in immunoglobulins was observed in the 600mg group, but gradually recovered at week 20. Three patients (2 in 100mg and 1 in 600mg group) were tested positive for anti-zuberitamab antibodies. We also observed that women, disease duration <12 months, and MAIPA+patients may have higher response rates. This study preliminarily confirmed that 100mg zuberitamab was safe and effective in treating ITP and was recommended to support further investigation. National Natural Science Foundation of China and Zhejiang Bioray Biopharmaceutical Co. Ltd.

Inhibition of the Renin-Angiotensin System Improves Response to Neoadjuvant Therapy in Patients With Liver Metastasis of Colorectal Cancers

IntroductionRenin-angiotensin-aldosterone system inhibitors (RAAS-I) have been shown to prolong overall survival in patients with liver metastasized colorectal cancer in combination with antiangiogenic treatment. The effects of RAAS-I combined with neoadjuvant chemotherapy on colorectal cancer liver metastasis remain unexplored. We aimed to study the response of patients undergoing liver resection to RAAS-I in combination with neoadjuvant therapy to elucidate their potential benefits. MethodsBetween February 2005 and May 2012, 62 patients fulfilled the inclusion criteria for distant metastasis (cM1) and comparable computed tomography or magnetic resonance tomography scans in the Picture Archiving Communication System of our center before and after neoadjuvant chemotherapy. Follow-up data and clinicopathological characteristics were collected from a prospective database and retrospectively investigated. The chemotherapeutic response to liver metastasis was evaluated according to the Response Evaluation Criteria in Solid Tumors criteria 1.1. ResultsComparing the average reduction of measured lesions, a significant response to chemotherapy was detected in the patients receiving RAAS-I (n = 24) compared to those who did not (n = 38) (P = 0.031). Interestingly, the effect was more distinctive when the size reduction was compared between high responses with more than 50% size reduction of all measured lesions (P = 0.011). In the subgroup analysis of patients receiving bevacizumab treatment, high responses to chemotherapy were observed only in the RAAS-I cohort (28.6% versus 0%, P = 0.022). ConclusionsFor neoadjuvantly treated patients, concomitant antihypertensive treatment with RAAS-I showed a higher total size reduction of liver metastasis as a sign of treatment response, especially in combination with antiangiogenic treatment with bevacizumab.

Yolk-shell microspheres perovskite Gd/Fe oxides with rich oxygen vacancies for ultra-sensitive properties in acetone detection

Acetone as a toxic and hazardous gas is widely appeared in life. In this paper, p-type Gd/Fe oxide yolk-shell microspheres were prepared by a one-step hydrothermal method. Characterization and test results shows that perovskite Gd/Fe oxides with yolk-shell microspheres possess abundant oxygen vacancies, which presents excellent acetone gas-sensitive performance. Among the obtained sensor, the optimal operating temperature of the S-4 (Gd0.77/Fe) sensor is reduced to 200 ℃, and the response value (S = 20) to 100 ppm acetone is improved by 5 times (compare to S-1). The lowest detection limit can be as low as 0.5 ppm, furthermore the sensor presents resist-humidity. Electron paramagnetic resonance (EPR) and x-ray photoelectron spectroscopy (XPS) results reveal that the ratio of Gd/Fe has a strong correlation with the content of oxygen vacancies. The rich oxygen vacancies control theory is the main reason for improving gas sensing performance in this work. The presence of oxygen vacancies effectively increases the active sites and further promotes intermolecular interactions. Overall, the sensor S-4 (Gd0.77/Fe) has an important potential in the detection of acetone in human breath with high response and low detection limit under high humidity environment.

지역사회 문제 해결형 바이오헬스케어 분야 디지털 리빙랩의 활용 방안 연구

Objectives The purpose of this study was to understand the importance of the Bio-healthcare Digital Living Lab for solving community problems and to suggest policy improvement so that it can be utilized based on the speci-alized fields of university. Methods From September 1 to October 10, 2022, the survey was conducted on 150 students enrolled in bio-healthcare courses at universities in the Jeonbuk region, as well as faculty and community industrial company related Bio-healthcare department. The collected data were analyzed using the IBM SPSS Statistic ver. 22.0 stat-istical program. Frequency analysis, descriptive statistics, χ-square, independent t-test, and 1-way ANOVA were performed to analyze the data. Results The study showed satisfaction with the community living environment at 3.68 out of 5. By gender, it was higher in men(3.77±0.90) than in women(3.62±0.85), and by age, it was highest in people in their 20s(3.86±0.80), and satisfaction tended to decrease as age increased. Among local issues, ‘culture/leisure’ was recognized as the most important in terms of quality of life(28.2%) and an area in urgent need of improvement(27.6%), and the area expected to have the greatest ripple effect if improved was ‘jobs/start-up’(33.9%). In addition, there was a stat-istical difference in areas requiring urgent improvement and areas with large ripple effects depending on age and status(p&lt;.05). They recognized that the bio-healthcare field would play an important role in resolving local is-sues(52.7%), and that local residents‘ participation was necessary in promoting it(70.4%), but the highest re-sponse was that they would consider their participation depending on the nature and direction of the project (48.8%). And, teenagers showed statistically significantly lowest scores in terms of possibility of solving local is-sues, possibility of improving quality of life, need for resident participation, and willingness to participate (p&lt;.05). Conclusions In process of promoting a digital living lab in the bio-healthcare, an accurate preliminary analysis of the needs of local community residents regarding its nature and direction is necessary. And, in promoting a digital living lab that solves community problems, universities must play a role in building a digital living lab infrastructure specialized in the bio-healthcare field while experimenting with technology, products, and services through com-munity linkage. Lastly, for the expansion and sustainability of community bio-healthcare living labs, it is necessary to plan a living lab platform that considers both the community's needs and the university's specialized fields, and it is need to develop into an infrastructure rather than a project type.

Real-time and highly responsive hydrogen mapping in pure Fe using TiO2 thin films

A hydrogen visualization method with high responsivity and chemical stability under atmospheric corrosion is necessary to inhibit hydrogen embrittlement, which can occur with hydrogen uptake of structural materials. In this study, a highly responsive hydrogen mapping technique for steels was successfully established using a TiO2 thin film and Pd intermediate layer. The color of the TiO2 film on the hydrogen-detection side changes during hydrogen charging on the hydrogen-entry side of the Fe specimen, indicating that the color changes were attributed to the hydrogen uptake of the Fe surface and subsequent introduction of hydrogen atoms to the TiO2 film. Considering the responsivity and visibility, the optimal thickness of the TiO2 film was determined to be 20 nm. As TiO2 is a chemically stable material, the proposed mapping technique can be used to monitor the hydrogen absorbed into metallic materials under outdoor conditions.

ZnIn2S4 Nanosheets for Efficient NO2 Detection at Room Temperature: Insights into the Role of Sulfur Vacancies.

Engineering atomic vacancies in metal sulfide semiconductors allows for the efficient tuning of their electronic and chemical properties. In this work, we synthesized hollow tubular structures constructed by bimetallic ZnIn2S4 using a metal-organic framework (MOF) as the template. We found that the sulfur vacancies in ZnIn2S4 enabled extremely fast NO2 detection with high response at room temperature (RT), and the material with high sulfur vacancy content delivers a 2 times higher response to 10 ppm NO2 than the device with low sulfur vacancy content. To unveil the crucial role played by sulfur vacancies, DFT calculations were conducted to reveal that sulfur vacancies greatly enhance the interaction and electron transfer between ZnIn2S4 and NO2. This study will provide hints for the engineering of bimetallic sulfide materials for low-power gas sensors at RT.

Influence of epinephrine reactivity to stress on meat quality in goats

Abstract The magnitude of physiological responses to a stressor can vary among individual goats within a herd; however, whether these differences can differentially affect meat quality is not known. This study was conducted to determine the influence of the magnitude of epinephrine response (ER) to acute stress on muscle metabolome and meat quality in goats. Male Spanish goats (6 mo old) were transported for 180 min. (N = 75 goats; 25 goats/day) to impose stress. Blood samples were obtained after transport for analysis of physiological responses. Goats were slaughtered using humane procedures and samples were collected for muscle metabolomics and meat quality analyses. The data obtained from blood and muscle/meat analysis were then categorized based on epinephrine concentrations into low (LE), medium (ME), and high (HE) epinephrine response groups (n = 12/ER group). The physiological and meat quality variables were analyzed as a Completely Randomized Design in SAS, and metabolomics data were analyzed using R software. Plasma glucose concentrations were significantly high in the HE group, low in the LE group, and intermediate in the ME group (P &amp;lt; 0.05). However, leukocyte counts and cortisol, norepinephrine, blood urea nitrogen, and creatine concentrations were not different among the ER groups. Muscle (Longissimus dorsi) glycogen concentrations (15 min postmortem) were significantly higher (P &amp;lt; 0.05) in the ME and LE groups than in the HE group. However, postmortem Longissimus muscle pH and temperature (15 min and 24 h), 24 h calpastatin and desmin levels, and rib chop color (L*, a*, and b*), cooking loss, and Warner-Bratzler shear force values were unaffected by ER. Targeted metabolomics analysis of Longissimus muscle (15 min) revealed that diacyl phosphatidylcholines (C38:0; 40:6) and sphingomyelin (C20:2) were significantly different (P &amp;lt; 0.05) among the ER groups, with the concentrations of these metabolites being consistently high in the LE group. These differential muscle metabolite concentrations suggest that ER can influence biochemical pathways associated with cell membrane integrity and signaling. Epinephrine response had a significant effect on dopamine concentrations, with the levels increasing with increasing levels of ER. The results indicate that differences in epinephrine reactivity can influence selected physiological responses and muscle metabolites; however, it does not significantly influence meat quality attributes.

Results of ponatinib as frontline therapy for chronic myeloid leukemia in chronic phase.

Ponatinib is a third-generation BCR::ABL1 tyrosine kinase inhibitor (TKI) with robust activity in Philadelphia chromosome-positive leukemias. Herein, we report the long-term follow-up of the phase 2 trial of ponatinib in chronic myeloid leukemia in chronic phase. Patients received ponatinib 30 to 45 mg/day. The primary end point was the rate of 6-month complete cytogenetic response (CCyR). The study was held in June 2014 because of the risk of cardiovascular toxicity, requiring patients to change TKI. Fifty-one patients were treated with ponatinib (median dose, 45 mg/day). Median age was 48 years (range, 21-75); 30 (59%) had baseline cardiovascular comorbidities. Median treatment duration was 13 months (range, 2-25). Fourteen patients (28%) discontinued ponatinib because of toxicities, 36 (71%) after the Food and Drug Administration warning/study closure, and one for noncompliance. Dasatinib was the most frequently chosen second-line TKI (n=34; 66%). Among 46 patients evaluable at 6 months, 44 (96%) achieved CCyR, 37 (80%) major molecular response, 28 (61%) MR4, and 21 (46%) MR4.5. The cumulative 6-month rates of CCyR, major molecular response, MR4, and MR4.5 were 96%, 78%, 50%, and 36%, respectively. Durable MR4 ≥24 or ≥60 months was observed in 67% and 51% of patients, respectively. The 24-month event-free survival rate was 97%. After a median follow-up of 128 months, the 10-year overall survival rate was 90%. Eight patients (16%) had serious grade 2 to 3 cardiovascular adverse events, leading to permanent discontinuation in five (10%). Ponatinib yielded high cytogenetic and molecular responses in newly diagnosed chronic myeloid leukemia in chronic phase. Its use in the frontline setting is hindered by arterio-/vaso-occlusive and other severe toxicities.

Atomically Precise Chiral Metal Nanoclusters for Circularly Polarized Light Detection

Circularly polarized light (CPL) detection is of great significance in various applications such as drug identification, sensing and imaging. Atomically precise chiral metal nanoclusters with intense circular dichroism (CD) signals are promising candidates for CPL detection, which can further facilitate device miniaturization and integration. Herein, we report the preparation of a pair of optically active chiral silver nanoclusters [Ag7(R/S‐DMA)2(dpppy)3] (BF4)3 (R/S‐Ag7) for direct CPL detection. The crystal structure and molecular formula of R/S‐Ag7 clusters are confirmed by single‐crystal x‐ray diffraction and high‐resolution mass spectrometry. R/S‐Ag7 clusters exhibit strong CD spectra and CPL luminescence both in solution and solid states. When used as the photoactive materials in photodetectors, R/S‐Ag7 enables effective discrimination between left‐handed circularly polarized and right‐handed circularly polarized light at 520 nm with short response time, high responsivity and considerable discrimination ratio. This study is the first report on using atomically precise chiral metal nanoclusters for CPL detection.

Atomically Precise Chiral Metal Nanoclusters for Circularly Polarized Light Detection.

Circularly polarized light (CPL) detection is of great significance in various applications such as drug identification, sensing and imaging. Atomically precise chiral metal nanoclusters with intense circular dichroism (CD) signals are promising candidates for CPL detection, which can further facilitate device miniaturization and integration. Herein, we report the preparation of a pair of optically active chiral silver nanoclusters [Ag7(R/S-DMA)2(dpppy)3] (BF4)3 (R/S-Ag7) for direct CPL detection. The crystal structure and molecular formula of R/S-Ag7 clusters are confirmed by single-crystal x-ray diffraction and high-resolution mass spectrometry. R/S-Ag7 clusters exhibit strong CD spectra and CPL luminescence both in solution and solid states. When used as the photoactive materials in photodetectors, R/S-Ag7 enables effective discrimination between left-handed circularly polarized and right-handed circularly polarized light at 520 nm with short response time, high responsivity and considerable discrimination ratio. This study is the first report on using atomically precise chiral metal nanoclusters for CPL detection.

Immune cell patterns before and after neoadjuvant immune checkpoint blockade combined with chemoradiotherapy in locally advanced esophageal squamous cell carcinoma

BackgroundNeoadjuvant immune checkpoint blockade (ICB) combined with chemoradiotherapy offers high pathologic complete response (pCR) rate for patients with locally advanced esophageal squamous cell carcinomas (ESCC). But the dynamic tumor immune microenvironment modulated by such neoadjuvant therapy remains unclear.Patients and methodsA total of 41 patients with locally advanced ESCC were recruited. All patients received neoadjuvant toripalimab combined with concurrent chemoradiotherapy. Matched pre- and post-treatment tissues were obtained for fluorescent multiplex immunohistochemistry (mIHC) and IHC analyses. The densities and spatial distributions of immune cells were determined by HALO modules. The differences of immune cell patterns before and after neoadjuvant treatment were investigated.ResultsIn the pre-treatment tissues, more stromal CD3 + FoxP3 + Tregs and CD86+/CD163 + macrophages were observed in patients with residual tumor existed in the resected lymph nodes (pN1), compared with patients with pCR. The majority of macrophages were distributed in close proximity to tumor nest in pN1 patients. In the post-treatment tissues, pCR patients had less CD86 + cell infiltration, whereas higher CD86 + cell density was significantly associated with higher tumor regression grades (TRG) in non-pCR patients. When comparing the paired pre- and post-treatment samples, heterogeneous therapy-associated immune cell patterns were found. Upon to the treatment, CD3 + T lymphocytes were slightly increased in pCR patients, but markedly decreased in non-pCR patients. In contrast, a noticeable increase and a less obvious decrease of CD86 + cell infiltration were respectively depicted in non-pCR and pCR patients. Furthermore, opposite trends of the treatment-induced alterations of CD8 + and CD15 + cell infiltrations were observed between pN0 and pN1 patients.ConclusionsCollectively, our data demonstrate a comprehensive picture of tumor immune landscape before and after neoadjuvant ICB combined with chemoradiotherapy in ESCC. The infiltration of CD86 + macrophage may serve as an unfavorable indicator for neoadjuvant toripalimab combined with chemoradiotherapy.

Induction Immunochemotherapy Yields a Higher Conversion Rate and Better Overall Survival than Chemotherapy in Initially Unresectable Esophageal Squamous Cell Carcinoma.

This study compared the surgical conversion rate and overall survival (OS) between induction chemotherapy (iC) and induction immunochemotherapy (iIC) for patients with initially unresectable esophageal squamous cell carcinoma (iuESCC). In this multicenter, retrospective cohort study, patients from four high-volume institutions with unresectable diseases were included. The primary endpoints were the conversion surgery rate and OS. A multivariate Cox regression analysis was used to identify the independent significant prognostic factors associated with OS. The stabilized inverse probability of treatment weighting was applied to confirm the survival comparison between the iIC and iC cohorts. A total of 309 patients (150 in the iIC cohort and 159 in the iC cohort) were included. A significantly higher conversion surgical rate was observed in the iIC cohort (iIC vs. iC: 127/150, 84.7% vs. 79/159, 49.7%, P < 0.001). The pathological complete response rates were 22.0% and 5.1% in the iIC and the iC cohorts, respectively (P = 0.001). A significant difference in the OS was observed between the iIC (not reached) and iC cohorts (median 95% CI 36.3 [range 27.2-45.5]). The stabilized inverse probability of treatment weighting yielded similar results. Regimen (iIC vs. iC, HR 0.215, 95% CI 0.102-0.454, P < 0.001) and operation (yes vs. no, HR 0.262, 95% CI 0.161-0.427, P < 0.001) were the significant prognostic factors for OS. Immunochemotherapy plus conversion surgery in the induction setting may be a better treatment option to achieve high pathological responses and improve OS in iuESCC patients.

Decoding the commutable first hyperpolarisability of keto–enol tautomer using DFT and AI-based soft computing method

ABSTRACT Non-linear optical (NLO) parameter of a series of donor–acceptor substituted N-salicylidene-4-benzenesulfonylaniline (SBSA) derivatives with a contrast of first hyperpolarisability has been investigated using density functional-based theory. The derivative of SBSA with both the donor and acceptor substitution (NMe2-SBSA-NO2) exhibits the highest first hyperpolarisability ( ∼ 3 × 103 a.u in gas phase) value. Frequency and solvent polarity responsive behaviours of first hyperpolarisability are utilised to demonstrate the variation of NLO as switchable electrical parameter. Each of the studied compounds displays very high NLO response at frequency corresponding to the absorption maxima of their electronic state. Likewise, the increase of solvent polarity induces a substantial increase of first hyperpolarisability. The computation of NLO responsive first hyperpolarisability by varying the frequency and solvent dielectric constant within a wide domain is very tedious and time-consuming. To overcome the lacuna, we implemented machine learning tools such as artificial neural networks (ANNs), fuzzy logic (FL) and adaptive neuro-fuzzy inference system (ANFIS) to predict the computation data of the NMe2-SBSA-NO2 and moderately good results were obtained using ANFIS as soft computing tool.

Phosphatidylserine Counteracts the High Stocking Density-Induced Stress Response, Redox Imbalance and Immunosuppression in Fish Megalobrama ambylsephala

Phosphatidylserine Counteracts the High Stocking Density-Induced Stress Response, Redox Imbalance and Immunosuppression in Fish Megalobrama ambylsephala

A voltage-driven dual-mode MoSe2 photodetector with graphene as van der Waals contact

Two-dimensional (2D) molybdenum selenide (MoSe2) is promising for use in the development of photodetectors for the harvesting of light from the ultraviolet to the near-infrared band, while high responsivity and fast response speed are difficult to simultaneously realize. Herein, we present a dual-mode MoSe2 photodetector with asymmetric electrodes, in which graphene and Cr metal are utilized as ohmic and Schottky contacts, respectively. The photodiode possesses fabulous Schottky characteristics, with a rectification ratio of ∼250 and a low dark current of ∼40 pA at −1 V. Under forward bias voltage of 1 V, the photodetector works in photoconductive mode with a slow response speed (decay time: ∼5 min) but high responsivity (632 mA W−1). However, at reverse bias voltage, the photodetector acts as a photovoltaic-type device due to the Schottky barrier between Cr and MoSe2. Because of the reinforced built-in electric field, the photodetector driven at −5 V shows much faster response speeds (rise time: 1.96 ms; decay time: 755 µs). This study provides a deep understanding of asymmetric structure MoSe2 photodetectors operated in two modes, which promotes a forward step toward 2D material optoelectronics.

Electronic 1 year follow up after ablation

Abstract Background Several studies have shown that phone calls are an effective but resource intensive Follow-up (FU) method to collect patient reported data (PROM) after discharge from hospital. Regarding patient preference for FU, who has been ablated for atrial fibrillation (AF), most of the AF patients favoured a questionnaire with a stamped return envelope. In 2019 the National registry for ablation and electrophysiology in Norway (AblaNor) was established. All patients who have been in an EP lab receive an electronic FU questionnaire (ePROM) 1 year after the date of ablation. In Norway, it has been developed a technical solution which allows data submitted from the patient to be registered in the Health Network,"ePROM engine". Little is known about the functionality and response rate of electronic solutions. Purpose The aim of our study was to investigate an electronic FU approach in general and in different patient subgroups from AblaNor. Method We used data from the National register of ablation and electrophysiologi in Norway, Ablanor. The data are FU questionnaire who all patients received 1 year after ablation. All questionares are the same, independent diagnosis group. The patients received the FU questionnaires electronically via Helse Norge.no. The data is based on registrations from 2020-21. Results The data shows that amongst the 7169 selected procedures in 2020 and 2021, 5235 completed the ePROM form . There is a difference in response rates for both age and sex alone. Younger women have a higher response rate than men of same age, whereas in older age groups,men have higher response rates than women . Patients who have been ablated for AF have a higher respons rate than other procedures. Patients who have only undergone an electrophysiological examination (EP) have the lowest response rate. Conclusion Mandatory follow-up 1 year after completion of the procedure takes place in electronic form and contains simple registration of PROMS. The response rate among patients is 78% over the two years. This indicates an extremely high level of digital competence and motivation among patients to provide feedback for completed treatment. This shows that there is a discrepancy for FU regarding patient who has been ablated for atrial fibrillation (AF) . Abbreviations RFA: Radiofrequency Ablation; FU: Follow-up; AF: Atrial fibrillation; PROM: Patient reported outcome Measurement

Poly3‐Hexylthiophene Titanium Dioxide (P3HT‐TiO2) Composite Sensor for High Response Detection of Ammonia at Room Temperature

AbstractGas sensors for ammonia (NH3) play a crucial role in the maintenance of air quality, preservation of the atmosphere, and evaluation of human health. However, the endeavor to attain a high level of sensitivity in detecting NH3 under ambient conditions remains a challenging task. In this work, poly(3‐hexylthiophene)s and titanium dioxide (P3HT‐TiO2) heterostructure NH3 gas‐sensitive material was prepared, and by drop‐casting the material onto a substrate with Au interdigital electrodes, a sensor for high‐response detection of NH3 at room temperature was constructed. The designed gas sensor exhibited a high response signal of 114.61 % toward 15 ppm NH3 at room temperature (25 °C) with good reproducibility, strong long‐term stability, and excellent selectivity. Moreover, by analyzing the response law of the sensor under different humidity conditions, it has been noted that both excessively high and excessively low levels of humidity adversely affect the sensor's response. The remarkable increase in NH3 sensing properties is attributed to the synergistic enhancement effect of P−N heterojunction formed between P3HT and TiO2. This NH3 gas sensor exhibits tremendous potential for use due to its straightforward structure and outstanding ammonia sensing performance.

Non-negligible Toxicity to Fish in the Early Life Stages Triggered by Aqueous Leachate of Takeaway Plastic Containers.

Ordering takeout is a growing social phenomenon and may raise public health concerns. However, the associated health risk of compounds leaching from plastic packaging is unknown due to the lack of chemical and toxicity data. In this study, 20 chemical candidates were tentatively identified in the environmentally relevant leachate from plastic containers through the nontargeted chemical analysis. Three main components with high responses and/or predicted toxicity were further verified and quantified, namely, 3,5-di-tert-butyl-4-hydroxycinnamic acid (BHC), 2,4-di-tert-butylphenol (2,4-DTBP), and 9-octadecenamide (oleamide). The toxicity to zebrafish larvae of BHC, a degradation product of a widely used antioxidant Irganox 1010, was quite similar to that of the whole plastic leachate. In the same manner, RNA-seq-based ingenuity analysis showed that the affected canonical pathways of zebrafish larvae were quite comparable between BHC and the whole plastic leachate, i.e., highly relevant to neurological disease, metabolic disease, and even behavioral disorder. Longer-term exposure (35 days) did not cause any effect on adult zebrafish but led to decreased hatching rate and obvious neurotoxicity in zebrafish offspring. Collectively, this study strongly suggests that plastic containers can leach out a suite of compounds causing non-negligible impacts on the early stages of fish via direct or parental exposure.

2D–3D heterostructure of PtS2−x /Ga2O3 and their band alignment studies for high performance and broadband photodetector

For deep ultraviolet (UV-C) photodetectors, gallium oxide (Ga2O3) is a suitable candidate owing to its intrinsic ultra-wide band gap and high stability. However, its detection is limited within the UV-C region, which restricts it to cover a broad range, especially in visible and near-infrared (NIR) region. Therefore, constructing a heterostructure of Ga2O3 with an appropriate material having a narrow band gap is a worthwhile approach to compensate for it. In this category, PtS2 group-10 transitional metal dichalcogenide stands at the top owing to its narrow band gap (0.25–1.65 eV), high mobility, and stability for heterostructure synthesis. Moreover, heterostructure with Ga2O3 sensing in UV and PtS2 broad response in visible and IR range can broaden the spectrum from UV to NIR and to build broadband photodetector. In this work, we fabricated a 2D–3D PtS2−x /Ga2O3 heterostructure based broadband photodetector with detection from UV-C to NIR region. In addition, the PtS2−x /Ga2O3 device shows a high responsivity of 38.7 AW−1 and detectivity of 4.8 × 1013 Jones under 1100 nm light illumination at 5 V bias. A fast response of 90 ms/86 ms illustrates the device’s fast speed. An interface study between the PtS2−x and Ga2O3 was conducted using x-ray photoelectron spectroscopy and ultraviolet photoelectron spectroscopy (UPS) which confirmed type-I band alignment. Finally, based on their band alignment study, a carrier transport mechanism was proposed at the interface. This work offers a new opportunity to fabricate large-area high-performance 2D–3D heterostructures based photodetectors for future optoelectronics devices.

Resistance to immune checkpoint inhibitors in colorectal cancer with deficient mismatch repair/microsatellite instability: misdiagnosis, pseudoprogression and/or tumor heterogeneity?

Colorectal carcinoma (CRC) with deficiency of the deficient mismatch repair (dMMR) pathway/ microsatellite instability (MSI) is characterized by a high mutation load and infiltration of immune cells in the tumor microenvironment. In agreement with these findings, clinical trials have demonstrated a significant activity of immune checkpoint inhibitors (ICIs) in dMMR/MSI metastatic CRC (mCRC) patients and, more recently, in CRC patients with early disease undergoing neoadjuvant therapy. However, despite high response rates and durable clinical benefits, a fraction of mCRC patients, up to 30%, showed progressive disease when treated with single agent anti-programmed cell death 1 (PD-1) antibody. This article discusses the three main causes that have been associated with early progression of dMMR/MSI mCRC patients while on treatment with ICIs, i.e., misdiagnosis, pseudoprogression and tumor heterogeneity. While pseudoprogression probably does not play a relevant role, data from clinical studies demonstrate that some dMMR/MSI CRC cases with rapid progression on ICIs may be misdiagnosed, underlining the importance of correct diagnostics. More importantly, evidence suggests that dMMR/MSI mCRC is a heterogeneous group of tumors with different sensitivity to ICIs. Therefore, we propose novel diagnostic and therapeutic strategies to improve the outcome of dMMR/MSI CRC patients.