Pore Environmental Modification by Amino Groups in Robust Microporous MOFs for SF6 Capturing and SF6/N2 Separation.

Capturing and separating the greenhouse gas SF6 from nitrogen N2 have significant greenhouse mitigation potential and economic benefits. We used a pore engineering strategy to manipulate the pore environment of the metal-organic framework (MOF) by incorporating organic functional groups (-NH2). This resulted in an enhanced adsorption of SF6 and separation of the SF6/N2 mixture in the MOF. The introduction of amino (-NH2) groups into YTU-29 resulted in a reduction of the Brunauer-Emmett-Teller surface but an increase in interactions with SF6 within the confined pores. Water-stable YTU-29-NH2 showed a significantly higher SF6 uptake (95.5 cm3/g) than YTU-29 (77.4 cm3/g). The results of the breakthrough experiments show that YTU-29-NH2 has a significantly improved separation performance for SF6/N2 mixtures, with a high SF6 capture of 0.88 mmol/g compared to 0.56 mmol/g by YTU-29. This improvement is due to the suitable pore confinement and accessible -NH2 groups on pore surfaces. Considering its excellent regeneration ability and cycling performance, ultrastable YTU-29-NH2 demonstrates great potential for SF6 capturing and SF6/N2 separation.

Genomic alteration discordance in the paired primary-recurrent ovarian cancers: based on the comprehensive genomic profiling (CGP) analysis.

PURPOSE: Ovarian cancer (OC) is characterized by a high recurrence rate, and homologous recombination deficiency (HRD) is an important biomarker in the clinical management of OC. We investigated the differences in clinical genomic profiles between the primary and platinum-sensitive recurrent OC (PSROC), focusing on HRD status. MATERIALS AND METHODS: A total of 40 formalin-fixed paraffin-embedded (FFPE) tissues of primary tumors and their first platinum-sensitive recurrence from 20 OC patients were collected, and comprehensive genomic profiling (CGP) analysis of FoundationOne®CDx (F1CDx) was applied to explore the genetic (dis)similarities of the primary and recurrent tumors. RESULTS: By comparing between paired samples, we found that genomic loss of heterozygosity (gLOH) score had a high intra-patient correlation (r2 = 0.79) and that short variants (including TP53, BRCA1/2 and NOTCH1 mutations), tumor mutational burden (TMB) and microsatellite stability status remained stable. The frequency of (likely) pathological BRCA1/2 mutations was 30% (12/40) in all samples positively correlated with gLOH scores, but the proportion of gLOH-high status (score > 16%) was 50% (10/20) and 55% (11/20) in the primary and recurrent samples, respectively. An additional 20% (4/20) of patients needed attention, a quarter of which carried the pathological BRCA1 mutation but had a gLOH-low status (gLOH < 16%), and three-quarters had different gLOH status in primary-recurrent pairs. Furthermore, we observed the PSROC samples had higher gLOH scores (16.1 ± 9.24 vs. 19.4 ± 11.1, p = 0.007), more CNVs (36.1% vs. 15.1% of discordant genomic alternations), and significant enrichment of altered genes in TGF-beta signaling and Hippo signaling pathways (p < 0.05 for all) than their paired primaries. Lastly, mutational signature and oncodrive gene analyses showed that the computed mutational signature similarity in the primary and recurrent tumors were best matched the COSMI 3 signature (Aetiology of HRD) and had consistent candidate cancer driver genes of MSH2, NOTCH1 and MSH6. CONCLUSION: The high genetic concordance of the short variants remains stable along OC recurrence. However, the results reveal significantly higher gLOH scores in the recurrent setting than in paired primaries, supporting further clinically instantaneity HRD assay strategy.

Molecular fingerprint and machine learning enhance high-performance MOFs for mustard gas removal.

Chemical warfare agents (CWAs), epitomized by the notoriously used mustard gas (HD), represent a class of exceptionally toxic chemicals whose airborne removal is paramount for battlefield safety. This study integrates high-throughput computational screening (HTCS) with advanced machine learning (ML) techniques to investigate the efficacy of metal-organic frameworks (MOFs) in adsorbing and capturing trace amounts of HD present in the air. Our approach commenced with a comprehensive univariate analysis, scrutinizing the impact of six distinct descriptors on the adsorption efficiency of MOFs. This analysis elucidated a pronounced correlation between MOF density and the Henry coefficient in the effective capture of HD. Then, four ML algorithms were employed to train and predict the performance of MOFs. The Random Forest (RF) algorithm demonstrates strong model learning and good generalization, achieving the best prediction result of 98.3%. In a novel exploratory stride, we incorporated a 166-bit MACCS molecular fingerprinting (MF) to identify critical functional groups within adsorbents. From the top 100 MOFs analyzed, 22 optimal functional groups were identified. Leveraging these insights, we designed three innovative substructures, grounded in these key functional groups, to enhance HD adsorption efficiency. In this work, the combination of MF and ML could provide a new direction for efficient screening of MOFs for the capture of HD in the air. The outcomes of this study offer substantial potential to revolutionize the domain of CWA capture. This represents a significant stride toward developing practical solutions that enhance both environmental protection and battlefield security.

Indoxyl sulfate exacerbates alveolar bone loss in chronic kidney disease through ferroptosis.

OBJECTIVES: The purpose of this study was to determine whether indoxyl sulfate (IS) is involved in alveolar bone deterioration and to elucidate the mechanism underlying alveolar bone loss in chronic kidney disease (CKD) patients. MATERIALS AND METHODS: Mice were divided into the control group, CP group (ligature-induced periodontitis), CKD group (5/6 nephrectomy), and CKD + CP group. The concentration of IS in the gingival crevicular fluid (GCF) was determined by HPLC. The bone microarchitecture was evaluated by micro-CT. MC3T3-E1 cells were stimulated with IS, and changes in mitochondrial morphology and ferroptosis-related factors were detected. RT-PCR, western blotting, alkaline phosphatase activity assays, and alizarin red S staining were utilized to assess how IS affects osteogenic differentiation. RESULTS: Compared with that in the other groups, alveolar bone destruction in the CKD + CP group was more severe. IS accumulated in the GCF of mice with CKD. IS activated the aryl hydrocarbon receptor (AhR) in vitro, inhibited MC3T3-E1 cell osteogenic differentiation, caused changes in mitochondrial morphology, and activated the SLC7A11/GPX4 signaling pathway. An AhR inhibitor attenuated the aforementioned changes induced by IS. CONCLUSIONS: IS activated the AhR/SLC7A11/GPX4 signaling pathway, inhibited osteogenesis in MC3T3-E1 cells, and participated in alveolar bone resorption in CKD model mice through ferroptosis.

[Retracted] MicroRNA­584 prohibits hepatocellular carcinoma cell proliferation and invasion by directly targeting BDNF.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the Transwell invasion assay data shown in Fig. 2C and D on p. 1997 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published, or were submitted for publication at around the same time (and in some cases, have subsequently been retracted).  Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a  reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports  20: 1994-2001, 2019; DOI: 10.3892/mmr.2019.10424].

Preparation of valine-curcumin conjugate and its in vitro antibacterial and antitumor activity and in vivo biological effects on American eels (Anguilla rostrata).

Curcumin (Cur) exhibits diverse natural pharmacological activities, despite its limited water solubility (hydrophobicity) and low bioavailability. In this investigation, a valine-curcumin conjugate (Val-Cur) was synthesized through amino acid side chain modification, and its solubility increased to 1.78 mg/mL. In vitro experimental findings demonstrated that the antibacterial activity of Val-Cur against Escherichia coli, Staphylococcus aureus, Aeromonas hydrophila, and Vibrio parahaemolyticus was significantly superior to that of Cur. The inhibition rate of Val-Cur against HepG2 (human hepatocellular carcinoma) cells was higher than that of Cur at low concentrations (below 25 µmol/L), although the IC50 value of Val-Cur did not differ significantly from that of Cur. In vivo biological effects of Val-Cur were assessed by adding it into the feed (150 mg/kg) of American eels (Anguilla rostrata). Val-Cur significantly improved the growth performance (↑weight gain rate, ↑specific growth rate, and ↓feed conversion rate) and activities of intestinal digestive enzymes (amylase and lipase) and antioxidant enzymes (superoxide dismutase) in American eels. Additionally, Val-Cur significantly improved serum biochemical indices (↑high-density lipoprotein cholesterol, ↓low-density lipoprotein cholesterol, ↓aspartate and alanine aminotransferases). Furthermore, Val-Cur increased intestinal microbial diversity, reduced the abundance of potentially pathogenic bacteria (Spiroplasma, Clostridium, and Pseudomonas), and elevated the abundance of beneficial digestion-promoting bacteria (Romboutsia, Phyllobacterium, Romboutsia sedimentorum, and Clostridium butyricum) conducive to glucose metabolism (P < 0.05). To the best of our knowledge, this study is the first to explore water-soluble curcumin in aquaculture, and the findings will lay the groundwork for the potential application of water-soluble curcumin in the field of aquaculture.

Novel MIP gene mutation causes autosomal-dominant congenital cataract.

AIM: To identify disease-causative mutations in families with congenital cataract. METHODS: Two Chinese families with autosomal-dominant congenital cataract (ADCC) were recruited and underwent comprehensive eye examinations. Gene panel next-generation sequencing of common pathogenic genes of congenital cataract was performed in the proband of each family. Sanger sequencing was used to valid the candidate gene mutations and sequence the other family members for co-segregation analysis. The effect of sequence changes on protein structure and function was predicted through bioinformatics analysis. Major intrinsic protein (MIP)-wildtype and MIP-G29R plasmids were constructed and microinjected into zebrafish single-cell stage embryos. Zebrafish embryonic lens phenotypes were screened using confocal microscopy. RESULTS: A novel heterozygous mutation (c.85G>A; p.G29R) in the MIP gene was identified in the proband of one family. A known heterozygous mutation (c.97C>T; p.R33C; rs864309693) in MIP was found in the proband of another family. In-silico prediction indicated that the novel mutation might affect the MIP protein function. Zebrafish embryonic lens was uniformly transparent in both wild-type PCS2+MIP and mutant PCS2+MIP. CONCLUSION: Two missense mutations in the MIP gene in Chinese cataract families are identified, and one of which is novel. These findings expand the genetic spectrum of MIP mutations associated with cataracts. The functional studies suggest that the novel MIP mutation might not be a gain-of-function but a loss-of-function mutation.

Vacciniumdehongense (Ericaceae), a new species of Vaccinium sect. Epigynium from western Yunnan, China.

Vacciniumdehongense (Ericaceae), a new species from Yingjiang County of Yunnan Province, China is described and illustrated. This new species belongs to Vacciniumsect.Epigynium and is most similar to V.vacciniaceum, but differs from the latter in the subsessile leaves, the inflorescence usually developing at leafless nodes, the shorter pedicels and the filaments being ca. 1/3 length of the stamens. Since the type locality of this new species is very near the border between China and Myanmar, it is probably also distributed in the adjacent area of Myanmar. As no population assessment of this species in its whole distribution area is made, it is best to assign a conservation status of 'Data Deficient' (DD) for this species.

Replenishment of mitochondrial Na+ and H+ by ionophores potentiates cutaneous wound healing in diabetes.

Diabetic foot ulcer (DFU) is a highly morbid complication in patients with diabetes mellitus, necessitating the development of innovative pharmaceuticals to address unmet medical needs. Sodium ion (Na+) is a well-established mediator for membrane potential and osmotic equilibrium. Recently, Na+ transporters have been identified as a functional regulator of regeneration. However, the role of Na+ in the intricate healing process of mammalian wounds remains elusive. Here, we found that the skin wounds in hyponatremic mice display a hard-to-heal phenotype. Na+ ionophores that were employed to increase intracellular Na+ content could facilitate keratinocyte proliferation and migration, and promote angiogenesis, exhibiting diverse biological activities. Among of them, monensin A emerges as a promising agent for accelerating the healing dynamics of skin wounds in diabetes. Mechanistically, the elevated mitochondrial Na+ decelerates inner mitochondrial membrane fluidity, instigating the production of reactive oxygen species (ROS), which is identified as a critical effector on the monensin A-induced improvement of wound healing. Concurrently, Na+ ionophores replenish H+ to the mitochondrial matrix, causing an enhancement of mitochondrial energy metabolism to support productive wound healing programs. Our study unfolds a new role of Na+, which is a pivotal determinant in wound healing. Furthermore, it directs a roadmap for developing Na+ ionophores as innovative pharmaceuticals for treating chronic dermal wounds in diabetic patients.

Shared genetic basis and causality between schizophrenia and inflammatory bowel disease: evidence from a comprehensive genetic analysis.

BACKGROUND: The comorbidity between schizophrenia (SCZ) and inflammatory bowel disease (IBD) observed in epidemiological studies is partially attributed to genetic overlap, but the magnitude of shared genetic components and the causality relationship between them remains unclear. METHODS: By leveraging large-scale genome-wide association study (GWAS) summary statistics for SCZ, IBD, ulcerative colitis (UC), and Crohn's disease (CD), we conducted a comprehensive genetic pleiotropic analysis to uncover shared loci, genes, or biological processes between SCZ and each of IBD, UC, and CD, independently. Univariable and multivariable Mendelian randomization (MR) analyses were applied to assess the causality across these two disorders. RESULTS: SCZ genetically correlated with IBD (rg = 0.14, p = 3.65 × 10−9), UC (rg = 0.15, p = 4.88 × 10−8), and CD (rg = 0.12, p = 2.27 × 10−6), all surpassed the Bonferroni correction. Cross-trait meta-analysis identified 64, 52, and 66 significantly independent loci associated with SCZ and IBD, UC, and CD, respectively. Follow-up gene-based analysis found 11 novel pleiotropic genes (KAT5, RABEP1, ELP5, CSNK1G1, etc) in all joint phenotypes. Co-expression and pathway enrichment analysis illustrated those novel genes were mainly involved in core immune-related signal transduction and cerebral disorder-related pathways. In univariable MR, genetic predisposition to SCZ was associated with an increased risk of IBD (OR 1.11, 95% CI 1.07­1.15, p = 1.85 × 10−6). Multivariable MR indicated a causal effect of genetic liability to SCZ on IBD risk independent of Actinobacteria (OR 1.11, 95% CI 1.06­1.16, p = 1.34 × 10−6) or BMI (OR 1.11, 95% CI 1.04­1.18, p = 1.84 × 10−3). CONCLUSIONS: We confirmed a shared genetic basis, pleiotropic loci/genes, and causal relationship between SCZ and IBD, providing novel insights into the biological mechanism and therapeutic targets underlying these two disorders.

Lipopolysaccharide binding protein resists hepatic oxidative stress by regulating lipid droplet homeostasis.

Oxidative stress-induced lipid accumulation is mediated by lipid droplets (LDs) homeostasis, which sequester vulnerable unsaturated triglycerides into LDs to prevent further peroxidation. Here we identify the upregulation of lipopolysaccharide-binding protein (LBP) and its trafficking through LDs as a mechanism for modulating LD homeostasis in response to oxidative stress. Our results suggest that LBP induces lipid accumulation by controlling lipid-redox homeostasis through its lipid-capture activity, sorting unsaturated triglycerides into LDs. N-acetyl-L-cysteine treatment reduces LBP-mediated triglycerides accumulation by phospholipid/triglycerides competition and Peroxiredoxin 4, a redox state sensor of LBP that regulates the shuttle of LBP from LDs. Furthermore, chronic stress upregulates LBP expression, leading to insulin resistance and obesity. Our findings contribute to the understanding of the role of LBP in regulating LD homeostasis and against cellular peroxidative injury. These insights could inform the development of redox-based therapies for alleviating oxidative stress-induced metabolic dysfunction.

The impact of pre-compression and temperature on perfluoroalkoxy alkane springs: Insights into spring relaxation.

A predictive model was proposed for determining the high-temperature free height of perfluoroalkoxy alkane springs in air-operated double-bellow pumps with the aim of investigating their relaxation. The model incorporates classical spring deformation theory and considers the material, structure, and real-world operating conditions of the perfluoroalkoxy alkane springs. Experimental validation of the model is also conducted. This study examines the effects of varying temperatures and pre-compression values on the relaxation of perfluoroalkoxy alkane springs' free height. It collects relaxation curves under different temperatures and various pre-compression conditions. The results indicate that spring relaxation increases with higher temperatures when there is no pre-compression. Furthermore, increasing pre-compression at the same temperatures leads to greater spring relaxation. Pre-compression has a more significant impact on spring relaxation. By comparing the experimental data with the simulated curve generated by the model, it is evident that the predicted spring free height relaxation closely aligns with the actual measurements. This verification demonstrates the effectiveness and accuracy of the proposed model in evaluating the relaxation of perfluoroalkoxy alkane springs' free height. Moreover, the model provides a valuable tool for predicting the lifespan of similar perfluoroalkoxy alkane springs in engineering applications.

[Environmental Benefits of Pollution and Carbon Reduction by Bus Fleet Electrification in Zhengzhou].

Electrification of bus fleets is an effective approach to reducing transportation-related pollution and carbon emissions. Evaluating the impact of electrification on existing bus fleets can provide valuable insights for promoting full electrification of public transportation in large cities. Utilizing the fuel life cycle method, we analyzed the CO2 and pollutant emissions of Zhengzhou's bus fleet before and after electrification and evaluated emissions under different electrification scenarios. Our results indicated that after electrification, the fuel life cycle CO2 and PM2.5 emissions increased by 32.6% and 42.6%, respectively, whereas CO, NOx, and VOC emissions decreased by 28%, 34%, and 25%, respectively. Optimizing the power generation structure is a critical factor in reducing CO2 and PM2.5 emissions during the electrification process. The best scenario for comprehensive electrification and power generation structure optimization could result in a 38.7% reduction in CO2, as well as reductions of 80.1% in CO, 84.4% in NOx, 92.2% in VOC, and 30.2% in PM2.5. Prioritizing electrification on long-distance routes is recommended during the replacement process. Additionally, replacing plug-in hybrid natural gas vehicles with pure electric vehicles has both advantages and disadvantages in terms of emission reduction. Achieving pollution reduction and carbon synergies requires advancing fleet replacement and power structure adjustments simultaneously.

Quantifying chemical correlations between fruits and processed fruit products: A non-targeted analysis approach.

Juices and beverages are produced by industry for long-distance distribution and shelf-stability, providing valuable nutrients. However, their nutritional value is often underestimated due to insufficient analytical methods. We have employed non-targeted analysis through a standardized analytical protocol, taking advantage of Data Independent Acquisition (DIA) technique and a novel Chromatographic Retention Behavior (CRB) data deconvolution algorithm. After analyzing 9 fruits and their products, correlations between fruits and their juices are accurately digitalized by similarities of their LC-MS fingerprints. We also specify non-targeted molecules primarily associate with nutrient loss in these analyzed juice products, including nitrogenous nutrients, flavonoids, glycosides, and vitamins. Moreover, we unveiled previously unreported fruit-characteristic metabolites, of which reconstituted-from-concentrate (RFC) juices contain over 40% of the content found in their fresh counterparts. Conclusively, our method establishes a quantitative benchmark for rational selection of RFC juices to substitute natural fruits.

An investigation for the efficacy of teaching model of combining virtual simulation and real experiment for clinical microbiology examination.

Background: As a convenient teaching tool, virtual simulation experiment technology had been widely utilized in the field of medical education. However, virtual learning could not fully replace the benefits of in-person instruction. Therefore, finding ways to integrate both methods was crucial for achieving optimal educational outcomes. The objective of this study was to compare the effectiveness of the self-built virtual simulation and design experiment combining teaching mode and the traditional experimental teaching mode in the clinical microbiology examination experiment teaching. Methods: This study was conducted at Shandong First Medical University in China. The experimental group consisted of 100 third-year students from the grade 2020 majoring in medical examination technology, who underwent an innovative teaching model combining virtual and real experiments. The control group comprised of 100 third-year students from the grade 2019 in the same major, who received traditional experimental teaching model. In this study, we referred to grade 2020 as cohort 2020 and grade 2019 cohort 2019. The performance of both groups was assessed via experimental and theoretical testing. Meanwhile, survey questionnaires were administered to evaluate the efficacy of the innovative experimental teaching model and students' level of satisfaction with it. Cohort 2020 conducted a survey for modules 1 to 4, while cohort 2019 only conducted a survey for module 4, as detailed in the Appendix. Results: The majority of students in the experimental group expressed satisfaction with the teaching model that combined virtual and real experiments, as evidenced by their superior performance on both experimental operational skills (87.54 ± 8.93 vs. 82.39 ± 10.55) and theoretical knowledge tests (83.65 ± 9.02 vs. 80.18 ± 8.24) compared to those in the control group. Conclusion: The combination of virtual simulation experiment and design experiment in the microbiological examination of clinical specimens represented an effective pedagogical approach. The instructional approach had the potential to incite a passion for learning, enhance proficiency in standardized experimental techniques, foster the ability to integrate theory with practice, and cultivate clinical reasoning skills.

A Fusion of Taq DNA Polymerase with the CL7 Protein from Escherichia coli Remarkably Improves DNA Amplification.

DNA polymerases are important enzymes that synthesize DNA molecules and therefore are critical to various scientific fields as essential components of in vitro DNA synthesis reactions, including PCR. Modern diagnostics, molecular biology, and genetic engineering require DNA polymerases with improved performance. This study aimed to obtain and characterize a new CL7-Taq fusion DNA polymerase, in which the DNA coding sequence of Taq DNA polymerase was fused with that of CL7, a variant of CE7 (Colicin E7 DNase) from Escherichia coli. The resulting novel recombinant open reading frame was cloned and expressed in E. coli. The recombinant CL7-Taq protein exhibited excellent thermostability, extension rate, sensitivity, and resistance to PCR inhibitors. Our results showed that the sensitivity of CL7-Taq DNA polymerase was 100-fold higher than that of wild-type Taq, which required a template concentration of at least 1.8 × 105 nM. Moreover, the extension rate of CL7-Taq was 4 kb/min, which remarkably exceeded the rate of Taq DNA polymerase (2 kb/min). Furthermore, the CL7 fusion protein showed increased resistance to inhibitors of DNA amplification, including lactoferrin, heparin, and blood. Single-cope human genomic targets were readily available from whole blood, and pretreatment to purify the template DNA was not required. Thus, this is a novel enzyme that improved the properties of Taq DNA polymerase, and thus may have wide application in molecular biology and diagnostics.

Genetic Links Between Metabolic Syndrome and Osteoarthritis: Insights from Cross-Trait Analysis.

BACKGROUND: Previous observational studies have indicated a bidirectional association between metabolic syndrome (MetS) and osteoarthritis (OA). However, it remains unclear whether these bidirectional associations reflect causal relationships or shared genetic factors, and the underlying biological mechanisms of this association are not fully understood. METHODS: Leveraging summary statistics from genome-wide association studies (GWASs) conducted by the UK Biobank and the Glucose and Insulin-related Traits Consortium (MAGIC), we performed global genetic correlation analyses, genome-wide cross-trait meta-analyses, and a bidirectional two-sample Mendelian randomization analyses using summary statistics from GWASs to comprehensively assess the relationship of MetS and OA. RESULTS: We first detected an extensive genetic correlation between MetS and OA (rg=0.393, P=1.52×10-18), which was consistent in four MetS components, including waist circumference, triglycerides, hypertension and high-density lipoprotein cholesterol and OA with rg ranging from -0.229 to 0.490. We then discovered 32 variants jointly associated with MetS and OA through multi-trait Analysis of GWAS. Co-localization analysis founded 12 genes shared between MetS and OA, with functional implications in several biological pathways. Finally, MR analysis suggested genetic liability to MetS significantly increased the risk of OA, but no reverse causality was found. CONCLUSION: Our results illustrate a common genetic architecture, pleiotropic loci, as well as causality between MetS and OA, potentially enhancing our knowledge of high comorbidity and genetic processes that overlap between the two disorders.

First-line sugemalimab with chemotherapy for advanced esophageal squamous cell carcinoma: a randomized phase 3 study.

Although antiprogrammed death 1 antibody plus chemotherapy has recently been approved for first-line esophageal squamous cell carcinoma (ESCC), antiprogrammed death-ligand 1 antibody may offer another combination option in this setting. In this multicenter, randomized, double-blinded phase 3 trial a total of 540 adults (aged 18-75 years) with unresectable, locally advanced, recurrent or metastatic ESCC and who had not received systemic treatment were enrolled. All patients were randomized at 2:1 to receive either sugemalimab (an anti-PD-L1 antibody; 1,200 mg) or placebo every 3 weeks for up to 24 months, plus chemotherapy (cisplatin 80 mg m-2 on day 1 plus 5-fluorouracil 800 mg m-2 day-1 on days 1-4) every 3 weeks for up to six cycles. At the prespecified interim analysis this study had met dual primary endpoints. With a median follow-up of 15.2 months, the prolongation of progression-free survival was statistically significant with sugemalimab plus chemotherapy compared with placebo plus chemotherapy (median 6.2 versus 5.4 months, hazard ratio 0.67 (95% confidence interval 0.54-0.82), P = 0.0002) as assessed by blinded independent central review. Overall survival was also superior with sugemalimab chemotherapy (median 15.3 versus 11.5 months, hazard ratio 0.70 (95% confidence interval 0.55-0.90, P = 0.0076). A significantly higher objective response rate (60.1 versus 45.2%) as assessed by blinded independent central review was observed with sugemalimab chemotherapy. The incidence of grade 3 or above treatment-related adverse events (51.3 versus 48.4%) was comparable between the two groups. Sugemalimab plus chemotherapy significantly prolonged progression-free survival and overall survival in treatment-naïve patients with advanced ESCC, with no unexpected safety signal. The ClinicalTrials.gov identifier is NCT04187352 .

Efficacy of anti-VEGF monotherapy versus anti-VEGF therapy with subthreshold micropulse laser (SML) in the management of diabetic macular oedema (DMO): a systematic review and meta-analysis.

BACKGROUND: Intravitreal injection anti-vascular endothelial growth factor (IVI anti-VEGF) therapy serves as the primary treatment for centre involving diabetic macular oedema (DMO). Conventional laser therapy (CLT) adjunct has proven beneficial; however, it is not widely used due to significant risks of retinal scarring. Subthreshold micropulse laser (SML) therapy has, however, emerged as a comparable alternative to combination therapy, offering a distinct advantage by mitigating the risk of retinal scarring. METHODS: A search of six databases was conducted. A meta-analysis of mean differences was performed including subgroup analyses where appropriate. Primary outcome was the number of injections at 12-14 months; secondary outcomes were changes in central macular thickness (CMT) and best corrected visual acuity (BCVA) at 6-8 months and 12-14 months. RESULTS: A total of ten papers including six randomised clinical trials and four retrospective clinical studies were included in our study, capturing 563 eyes of 478 patients. Overall, the risk of bias was moderate for these studies. Significantly fewer anti-VEGF therapy injections were administered in the combination therapy versus anti-VEGF monotherapy patients at 12-14 months who had poor visual acuity (6/18 Snellen or worse) at baseline, mean difference - 2.25 (95% CI; - 3.35, - 1.15; p < 0.05). Combination therapy was not associated with significantly fewer intravitreal injections in patients with a higher visual acuity (6/15 Snellen or better) at baseline. Our analysis also showed significant improvements to both BCVA and CMT were reached at 6 - 8 month post-baseline at the 95% confidence intervals: - 1.13 (- 2.09, - 0.16) and - 4.04 (- 7.59, - 0.50). These improvements remained statistically significant at 12-14 months: - 0.94 (- 1.67, - 0.20) and - 1.92 (- 3.52, - 0.32) respectively with combination therapy. CONCLUSION: Our findings demonstrate that combination therapy (SML + IVI anti-VEGF) is associated with fewer intravitreal injections. We report a better BCVA and a reduction in CMT at 6 and 12 months from baseline with combination treatment compared to the IVI anti-VEGF monotherapy comparator. SML is a proven non-scarring cost-effective therapy for DMO that should be readily available in the medical retinal therapy as it may reduce the burden of care.

CuS/Bi2O3 composites activating PMS under visible light for efficient degradation of antibiotic tetracycline.

CuS/Bi2O3 composite photocatalyst was prepared by calcination and in situ precipitation, and peroxymonosulfate (PMS) was applied to the degradation of tetracycline (TC) wastewater under visible light. The microscopic morphology, chemical composition, and optical properties of the composites were investigated by characterization means of XRD, FTIR, SEM, XPS, and UV-Vis DRS. The results showed that the introduction of CuS increased the specific surface area of Bi2O3 and increased the visible absorption boundary of Bi2O3 from 455 to 524 nm, which effectively inhibited the complexation of photogenerated electron-hole pairs. The experimental results showed that the introduction of PMS strengthened the removal of TC from the composites, and 95% of TC could be removed under visible light irradiation, and the reaction rate was 8.22 times higher than that of the unspiked PMS, indicating that the BC-15+vis/PMS catalytic system could degrade the pollutants efficiently. The radical capture experiments showed that several radicals, including ·OH, SO4·-, ·O2-, h+, and 1O2, were present in the catalytic system as the main active species to degrade TC, and the mechanism of photocatalytic activation of PMS by Z-type heterostructures of CuS/Bi2O3 composites was proposed. The present study showed that BC-15 has excellent degradation performance and stability, which provides new ideas for the treatment of antibiotic wastewater.