Fixed-Duration Pirtobrutinib plus Venetoclax with or without Rituximab in Relapsed/Refractory CLL: Phase 1b BRUIN Trial.

Pirtobrutinib is a highly selective, non-covalent (reversible) Bruton tyrosine kinase inhibitor (BTKi). Patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) were treated with fixed-duration pirtobrutinib plus venetoclax (PV) or pirtobrutinib plus venetoclax and rituximab (PVR) in this phase 1b trial (NCT03740529). Prior covalent BTKi therapy was allowed, but not prior venetoclax. Patients were assigned to receive PV (n=15) or PVR (n=10) for 25 cycles. Median age was 66 years (range, 39-78). Median prior lines of therapy was 2 (range, 1-4), and 17 (68%) patients had received prior covalent BTKi. At the data-cutoff date (May 5, 2023), median time on study was 27.0 months for PV and 23.3 months for PVR. Overall response rates were 93.3% (95% CI:68.1-99.8%) for PV and 100% (95% CI:69.2-100.0%) for PVR, with 10 complete responses (PV:7; PVR:3). After 12 cycles of treatment, 85.7% (95% CI:57.2-98.2%) of PV and 90.0% (95% CI:55.5-99.7%) of PVR patients achieved undetectable minimal residual disease assessed in peripheral blood by clonoSEQ® assay at a sensitivity of <1x10-4. Progression-free survival at 18 months was 92.9% (95% CI: 59.1-99.0) for PV patients and 80.0% (95% CI: 40.9-94.6) for PVR patients. No DLTs were observed in either treatment combination during the 5-week assessment period. The most common grade ≥3 adverse events for all patients included neutropenia (52%) and anemia (16%). Adverse events led to dose reduction in 3 patients and discontinuation in 2. In conclusion, fixed-duration PV or PVR was well tolerated and had promising efficacy in patients with R/R CLL, including patients previously treated with a covalent BTKi.

Transcription factor GmAlfin09 regulates endoplasmic reticulum stress in soybean via peroxidase GmPRDX6.

Soybean (Glycine max [L.] Merr.) is a valuable oil crop but is also highly susceptible to environmental stress. Thus, developing approaches to enhance soybean stress resistance is vital to soybean yield improvement. In previous studies, transcription factor Alfin has been shown to serve as an epigenetic regulator of plant growth and development. However, no studies on Alfin have yet been reported in soybean. In this study, the endoplasmic reticulum (ER) stress- and reactive oxygen species (ROS)-related GmAlfin09 was identified. Screening of genes co-expressed with GmAlfin09 unexpectedly led to the identification of soybean peroxidase 6 (GmPRDX6). Further analyses revealed that both GmAlfin09 and GmPRDX6 were responsive to ER stress, with GmPRDX6 localizing to the ER under stress. Promoter binding experiments confirmed the ability of GmAlfin09 to bind to the GmPRDX6 promoter directly. When GmAlfin09 and GmPRDX6 were overexpressed in soybean, enhanced ER stress resistance and decreased ROS levels were observed. Together, these findings suggest that GmAlfin09 promotes the upregulation of GmPRDX6, and GmPRDX6 subsequently localizes to the ER, reduces ROS levels, promotes ER homeostasis, and ensures the normal growth of soybean even under ER stress. This study highlights a vital target gene for future molecular breeding of stress-resistant soybean lines.

PLD2 deletion ameliorates sepsis-induced cardiomyopathy by suppressing cardiomyocyte pyroptosis via the NLRP3/caspase 1/GSDMD pathway.

OBJECTIVE: Sepsis-induced cardiomyopathy (SICM) is a life-threatening complication. Phospholipase D2 (PLD2) is crucial in mediating inflammatory reactions and is associated with the prognosis of patients with sepsis. Whether PLD2 is involved in the pathophysiology of SICM remains unknown. This study aimed to investigate the effect of PLD2 knockout on SICM and to explore potential mechanisms. METHODS: The SICM model was established using cecal ligation and puncture in wild-type and PLD2-knockout mice and lipopolysaccharide (LPS)-induced H9C2 cardiomyocytes. Transfection with PLD2-shRNA lentivirus and a PLD2 overexpression plasmid were used to interfere with PLD2 expression in H9C2 cells. Cardiac pathological alterations, cardiac function, markers of myocardial injury, and inflammatory factors were used to evaluate the SICM model. The expression of pyroptosis-related proteins (NLRP3, cleaved caspase 1, and GSDMD-N) was assessed using western blotting, immunofluorescence, and immunohistochemistry. RESULTS: SICM mice had myocardial tissue damage, increased inflammatory response, and impaired heart function, accompanied by elevated PLD2 expression. PLD2 deletion improved cardiac histological changes, mitigated cTNI production, and enhanced the survival of the SICM mice. Compared with controls, PLD2-knockdown H9C2 exhibits a decrease in inflammatory markers and lactate dehydrogenase production, and scanning electron microscopy results suggest that pyroptosis may be involved. The overexpression of PLD2 increased the expression of NLRP3 in cardiomyocytes. In addition, PLD2 deletion decreased the expression of pyroptosis-related proteins in SICM mice and LPS-induced H9C2 cells. CONCLUSION: PLD2 deletion is involved in SICM pathogenesis and is associated with the inhibition of the myocardial inflammatory response and pyroptosis through the NLRP3/caspase 1/GSDMD pathway.

GOLPH3 inhibits erastin-induced ferroptosis in colorectal cancer cells.

Ferroptosis is a novel form of programmed cell death and is considered to be a druggable target for colorectal cancer (CRC) therapy. However, the role of ferroptosis in CRC and its underlying mechanism are not fully understood. In the present study we found that a protein enriched in the Golgi apparatus, Golgi phosphoprotein 3 (GOLPH3), was overexpressed in human CRC tissue and in several CRC cell lines. The expression of GOLPH3 was significantly correlated with the expression of ferroptosis-related genes in CRC. The overexpression of GOLPH3 in Erastin-induced Caco-2 CRC cells reduced ferroptotic phenotypes, whereas the knockdown of GOLPH3 potentiated ferroptosis in HT-29 CRC cells. GOLPH3 induced the expression of prohibitin-1 (PHB1) and prohibitin-2 (PHB2), which also inhibited ferroptosis in Erastin-treated CRC cells. Moreover, GOLPH3 interacted with PHB2 and nuclear factor erythroid 2-related factor 2 (NRF2) in Caco-2 cells. These observations indicate that GOLPH3 is a negative regulator of ferroptosis in CRC cells. GOLPH3 protects these cells from ferroptosis by inducing the expression of PHB1 and PHB2, and by interacting with PHB2 and NRF2.

Safety of Extended Pirtobrutinib Exposure in Relapsed and/or Refractory B-Cell Malignancies.

INTRODUCTION: Pirtobrutinib, a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor, has demonstrated promising efficacy in B-cell malignancies and is associated with low rates of discontinuation and dose reduction. Pirtobrutinib is administered until disease progression or toxicity, necessitating an understanding of the safety profile in patients with extended treatment. METHODS: Here we report the safety of pirtobrutinib in patients with relapsed/refractory B-cell malignancies with extended (≥12 months) drug exposure from the BRUIN trial. Assessments included median time-to-first-occurrence of adverse events (AEs), dose reductions, and discontinuations due to treatment-emergent AEs (TEAEs) and select AEs of interest (AESIs). RESULTS: Of 773 patients enrolled, 326 (42%) received treatment for ≥12 months. In the extended exposure cohort, the median time-on-treatment was 19 months. The most common all-cause TEAEs were fatigue (32%) and diarrhea (31%). TEAEs leading to dose reduction occurred in 23 (7%) and discontinuations in 11 (3%) extended exposure patients. One patient had a fatal treatment-related AE (COVID-19 pneumonia). Infections (73.0%) were the most common AESI with a median time-to-first-occurrence of 7.4 months. Majority of TEAEs and AESIs occurred during the first year of therapy. CONCLUSIONS: Pirtobrutinib therapy continues to demonstrate an excellent safety profile amenable to long-term administration without evidence of new or worsening toxicity signals.

Characteristic and mechanism of biological nitrogen and phosphorus removal facilitated by biogenic manganese oxides (BioMnOx) at various concentrations of Mn(II).

Biogenic manganese oxides (BioMnOx) have attracted considerable attention as active oxidants, adsorbents, and catalysts. However, characteristics and mechanisms of nitrification-denitrification in biological redox reactions mediated by different concentrations of BioMnOx are still unclear. Fate of nutrients (e.g., NH4+-N, TP, NO3--N) and COD were investigated through different concentrations of BioMnOx produced by Mn(II) in the moving bed biofilm reactor (MBBR). 34% and 89.2%, 37.8% and 89.8%, 57.3% and 88.9%, and 62.1% and 90.4% of TN and COD by MBBR were synchronously removed in four phases, respectively. The result suggested that Mn(II) significantly improved the performance of simultaneous nitrification and denitrification (SND) and TP removal based on manganese (Mn) redox cycling. Characteristics of glutathione peroxidase (GSH-Px), reactive oxygen species (ROS), and electron transfer system activity (ETSA) were discussed, demonstrating that ROS accumulation reduced the ETSA and GSH-Px activities when Mn(II) concentration increased. Extracellular polymeric substance (EPS) function and metabolic pathway of Mn(II) were explored. Furthermore, effect of cellular components on denitrification was evaluated including BioMnOx performances, indicating that Mn(II) promoted the non-enzymatic action of cell fragments. Finally, mechanism of nitrification and denitrification, denitrifying phosphorus and Mn removal was further elucidated through X-ray photoelectron spectroscopy (XPS), high throughput sequencing, and fourier transform infrared reflection (FTIR). This results can bringing new vision for controlling nutrient pollution in redox process of Mn(II).

Microcystin-RR promote lipid accumulation through CD36 mediated signal pathway and fatty acid uptake in HepG2 cells.

Microcystins (MC)-RR is a significant analogue of MC-LR, which has been identified as a hepatotoxin capable of influencing lipid metabolism and promoting the progression of liver-related metabolic diseases. However, the toxicity and biological function of MC-RR are still not well understood. In this study, the toxic effects and its role in lipid metabolism of MC-RR were investigated in hepatoblastoma cells (HepG2cells). The results demonstrated that MC-RR dose-dependently reduced cell viability and induced apoptosis. Additionally, even at low concentrations, MC-RR promoted lipid accumulation through up-regulating levels of triglyceride, total cholesterol, phosphatidylcholines and phosphatidylethaolamine in HepG2 cells, with no impact on cell viability. Proteomics and transcriptomics analysis further revealed significant alterations in the protein and gene expression profiles in HepG2 cells treated with MC-RR. Bioinformatic analysis, along with subsequent validation, indicated the upregulation of CD36 and activation of the AMPK and PI3K/AKT/mTOR in response to MC-RR exposure. Finally, knockdown of CD36 markedly ameliorated MC-RR-induced lipid accumulation in HepG2 cells. These findings collectively suggest that MC-RR promotes lipid accumulation in HepG2 cells through CD36-mediated signal pathway and fatty acid uptake. Our findings provide new insights into the hepatotoxic mechanism of MC-RR.

Long-term exposure to ambient fine particulate matter and periodontitis: An observational study using nationally representative survey data.

AIM: The rising prevalence of periodontitis imposes substantial burdens on individuals and society. Identifying environmental risk factors for periodontitis may contribute to tackling the global public health burden of it. This study aimed to assess the association between long-term exposure to PM2.5 and periodontitis in a nationally representative population from China. MATERIALS AND METHODS: In this multi-centre cross-sectional study of 372 communities in 31 provinces of Mainland China, we used data from the Fourth National Oral Health Survey of China in 2015-2016, in combination with high-resolution gridded concentrations of fine particulate matter (PM2.5). Logistic regression was applied to assess the relationship between long-term PM2.5 exposure and the risk of periodontitis. In addition, we examined whether the association varied by individual characteristics, and estimated the exposure-response relationship and the risk of damaged tooth in each tooth quadrant. RESULTS: A total of 8391 participants from 96 cities were diagnosed with periodontitis, accounting for 60.04% (8391/13,459) of the participants. For each 10 µg/m3 increment in 1-, 3- and 5-year average concentrations of PM2.5, the risk of total periodontitis increased by 9.0% (95% confidence interval: 6.0%, 12.0%), 8.0% (6.0, 11·0) and 7.0% (5.0, 10.0), respectively. Mild periodontitis was more strongly associated with PM2.5 exposure than moderate and severe periodontitis. The teeth in the lower anterior, lower posterior or upper anterior are more susceptible to the effect of PM2.5 on the periodontal pocket, calculus and bleeding gums. CONCLUSIONS: Long-term exposure to PM2.5 is significantly associated with an increased risk of periodontitis in the nationally representative Chinese population. Considering the rising prevalence of periodontitis, considerable costs of treatment, and substantially adverse effects on individuals and society, these findings suggest that stricter air quality regulations may help ease the burden of periodontal disease.

Triphenyl phosphate (TPP) exposure promotes proliferation and migration capabilities of gastric cancer cells: Insights from gene expression and pathway analysis.

BACKGROUND: Gastric cancer is a leading cause of cancer-related deaths influenced by both genetic and environmental factors. Triphenyl phosphate (TPP) is a prevalent flame retardant, but its health implications remain to be thoroughly understood. OBJECTIVE: To explore the link between TPP exposure and gastric cancer by examining gene expression patterns and developing a predictive model. METHODS: Gene expression data were sourced from The Cancer Genome Atlas (TCGA) and the Comparative Toxicogenomics Database (CTD). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were employed for analysis. Single-sample Gene Set Enrichment Analysis (ssGSEA) was used to obtain phosphate flame retardant-related scores. A predictive model was constructed through differential analysis, univariate COX regression, and LASSO regression. Molecular docking was performed to assess protein interactions with TPP. RESULTS: ssGSEA identified scores related to phosphate flame retardants in gastric cancer, which had a strong association with immune-related traits. Several genes associated with TPP were identified and used to develop a prognostic model that has clinical significance. Molecular docking showed a high binding affinity of TPP with MTTP, a gene related to lipid metabolism. Pathway analysis indicated that TPP exposure contributes to gastric cancer through lipid metabolic processes. CONCLUSION: The study establishes a potential correlation between TPP exposure and gastric cancer onset, pinpointing key genes and pathways involved. This underscores the significance of environmental factors in gastric cancer research and presents a potential diagnostic tool for clinical application.

Screening significance of systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) in coronary heart disease of symptomatic youth.

BACKGROUND: The incidence of coronary heart disease (CHD) in youth is rapidly increasing but difficultly recognized in the early stage. METHODS AND RESULTS: In this retrospective study, 194 CHD patients under the age of 45 who previously experienced chest pain symptoms and 170 non-CHD patients were included and demographic data were collected. Systemic inflammation index (SII) and systemic inflammation response index (SIRI) were increased in young CHD patients (p < 001). Spearman's correlation analysis showed that both SII and SIRI were negatively correlated with HDL and positively correlated with hypertension, Gensini score, and hsTnI. Logistic regression analysis indicated that SII and SIRI were independently associated with the presence of CHD in youth with chest pain symptoms. The area under the ROC curve (AUC) of the SII model for young CHD patients was 0.805 (0.728-0.869), and the sensitivity and specificity were 0.65 and 0.823, respectively. Meanwhile, the AUC for the SIRI model was 0.812 (0.739-0.872), and the sensitivity and specificity were 0.673 and 0.8022. The calibration curves of both SII and SIRI models are in good agreement with the actual curves. And the decision curves of both models indicated their clinical practicality. CONCLUSION: SII and SIRI are independent risk factors for CHD in young adults, which can quickly and effectively identify CHD patients among young adults who have previously experienced chest pain symptoms.

ENST00000534735 inhibits proliferation and migration, promotes apoptosis and pyroptosis of endometrial cancer via OSBPL3 through APMK/SIRT1/NF-κB pathway.

Background: The complete understanding of the biological roles of long non-coding RNAs (lncRNAs) in cancer remains elusive. The findings of this study indicate that the newly discovered lncRNA ENST00000534735 exhibited a decreased expression in both endometrial cancer (EC) tissues and cell lines. Methods: The expression of ENST00000534735 in EC tissues was detected using RNA-sequencing analysis. The effects of ENST00000534735 on cell proliferation, migration, apoptosis, and pyroptosis were determined via in vitro and in vivo experiments. The proteins that interact with ENST00000534735 were confirmed by RNA pull-down assay. Furthermore, an investigation was conducted on the impact of ENST00000534735 on the in vivo growth of EC through a tumorigenicity assay in nude mice. Results: We found that ENST00000534735 was significantly down-regulated in EC tissues compared to their adjacent non-cancerous tissues. The ectopic expression of ENST00000534735 drastically inhibited lung cancer cell proliferation and migration ability and facilitated apoptosis and pyroptosis. Knockdown of ENST00000534735 increased OSBPL3 expression, and the tumor-suppressing effects of ENST00000534735 overexpression were reversed by upregulation of OSBPL3 via the APMK/SIRT1/NF-κB pathway. The in vivo tumorigenic assays conducted on nude mice revealed that the excessive expression of ENST00000534735 impeded the growth of EC. Conclusions: All results elucidated the role and molecular mechanism of ENST00000534735 in the malignant development of EC. ENST00000534735, a new antioncogene in EC, may serve as a survival biomarker or therapeutic target for EC.

Targeted Delivery of Quinoxaline-Based Semiconducting Polymers for Tumor Photothermal Therapy.

Photothermal therapy (PTT) holds great potential in the field of cancer treatment due to its high specificity and low invasiveness. However, the low conversion efficiency, inadequate tumor accumulation, and limited cellular uptake continue to impede PTT effectiveness in treating tumors. The present study focuses on the utilization of quinoxaline and its nanoparticles to develop an organic semiconducting photothermal agent (PAQI-BDTT) for tumor photothermal therapy. To achieve this, PAQI-BDTT was encapsulated within liposomes modified with cyclic Arg-Gly-Asp (cRGD) peptide targeting tumors (named T-BDTT-Lipo). Notably, T-BDTT-Lipo demonstrated a positive photothermal conversion efficiency of 74% when exposed to an 808 nm laser, along with NIR-II fluorescence imaging capabilities. The efficacy of T-BDTT-Lipo in tumor tissue accumulation and precise targeting of malignant cells has been confirmed through both in vitro and in vivo experiments guided by fluorescence imaging. Under single dose and 808 nm light irradiation, T-BDTT-Lipo generated local intracellular hyperthermia at the tumor site. The elevated temperature additionally exerted a significant inhibitory effect on tumor growth and recurrence, thereby extending the survival duration of mice harboring tumors. The therapeutic nanosystem (T-BDTT-Lipo) proposed in this work demonstrates the enormous potential of semiconducting photothermal agents in photothermal therapy, laying the foundation for the next clinical application.

Effects of operational parameters on bacterial communities in Hong Kong and global wastewater treatment plants.

Wastewater treatment plants (WWTPs) are indispensable biotechnology facilities for modern cities and play an essential role in modern urban infrastructure by employing microorganisms to remove pollutants in wastewater, thus protecting public health and the environment. This study conducted a 13-month bacterial community survey of six full-scale WWTPs in Hong Kong with samples of influent, activated sludge (AS), and effluent to explore their synchronism and asynchronism of bacterial community. Besides, we compared AS results of six Hong Kong WWTPs with data from 1,186 AS amplicon data in 269 global WWTPs and a 9-year metagenomic sequencing survey of a Hong Kong WWTP. Our results showed the compositions of bacterial communities varied and the bacterial community structure of AS had obvious differences across Hong Kong WWTPs. The co-occurrence analysis identified 40 pairs of relationships that existed among Hong Kong WWTPs to show solid associations between two species and stochastic processes took large proportions for the bacterial community assembly of six WWTPs. The abundance and distribution of the functional bacteria in worldwide and Hong Kong WWTPs were examined and compared, and we found that ammonia-oxidizing bacteria had more diversity than nitrite-oxidizing bacteria. Besides, Hong Kong WWTPs could make great contributions to the genome mining of microbial dark matter in the global "wanted list." Operational parameters had important effects on OTUs' abundance, such as the temperature to the genera of Tetrasphaera, Gordonia and Nitrospira. All these results obtained from this study can deepen our understanding of the microbial ecology in WWTPs and provide foundations for further studies. IMPORTANCE: Wastewater treatment plants (WWTPs) are an indispensable component of modern cities, as they can remove pollutants in wastewater to prevent anthropogenic activities. Activated sludge (AS) is a fundamental wastewater treatment process and it harbors a highly complex microbial community that forms the main components and contains functional groups. Unveiling "who is there" is a long-term goal of the research on AS microbiology. High-throughput sequencing provides insights into the inventory diversity of microbial communities to an unprecedented level of detail. At present, the analysis of communities in WWTPs usually comes from a specific WWTP and lacks comparisons and verification among different WWTPs. The wide-scale and long-term sampling project and research in this study could help us evaluate the AS community more accurately to find the similarities and different results for different WWTPs in Hong Kong and other regions of the world.

Principles and Design of Bionic Hydrogel Adhesives for Skin Wound Treatment.

Over millions of years of evolution, nature has developed a myriad of unique features that have inspired the design of adhesives for wound healing. Bionic hydrogel adhesives, capable of adapting to the dynamic movements of tissues, possess superior biocompatibility and effectively promote the healing of both external and internal wounds. This paper provides a systematic review of the design and principles of these adhesives, focusing on the treatment of skin wounds, and explores the feasibility of incorporating nature-inspired properties into their design. The adhesion mechanisms of bionic adhesives are analyzed from both chemical and physical perspectives. Materials from natural and synthetic polymers commonly used as adhesives are detailed regarding their biocompatibility and degradability. The multifunctional design elements of hydrogel adhesives for skin trauma treatment, such as self-healing, drug release, responsive design, and optimization of mechanical and physical properties, are further explored. The aim is to overcome the limitations of conventional treatments and offer a safer, more effective solution for the application of bionic wound dressings.

Protosappanin B enhances the chemosensitivity of 5-fluorouracil in colon adenocarcinoma by regulating the LINC00612/microRNA-590-3p/Golgi phosphoprotein 3 axis.

BACKGROUND: 5-fluorouracil (5-FU) is conventionally used in chemotherapy for colon adenocarcinomas. Acquired resistance of 5-FU remains a clinical challenge in colon cancer, and efforts to develop targeted agents to reduce resistance have not yielded success. Protosappanin B (PSB), the main component of Lignum Sappan extract, is known to exhibit anti-tumor effects. However, whether and how PSB could improve 5-FU resistance in colon cancer have not yet been established. In this study, we aimed to explore the effects and underlying mechanisms of PSB in 5-FU-induced chemoresistance in colon adenocarcinoma. METHODS: Forty-seven paired colon cancer tissue samples from patients who received 5-FU chemotherapy were collected as clinical samples. Two 5-FU resistant colon cancer cell lines were established for in vitro experiments. Reverse transcription-quantitative PCR (RT-qPCR) was performed to determine the mRNA and microRNA (miRNA) expression levels in colon adenocarcinoma tissues and cell lines. Cell Counting Kit-8 (CCK-8) and flow cytometry assays were performed to evaluate cell proliferation and apoptosis, respectively. RESULTS: LINC00612 was highly expressed in colon adenocarcinoma samples and 5-FU resistant colon cancer cells. LINC00612 knockdown enhances 5-FU chemosensitivity in 5-FU resistant cells. Notably, PSB treatment attenuated LINC00612 expression in 5-FU resistant colon adenocarcinoma cells. Moreover, PSB treatment reversed the increase in LINC00612-induced 5-FU resistance. Mechanistically, LINC00612 specifically bound to miR-590-3p, which promoted 5-FU resistance in colon adenocarcinoma cells and attenuated the inhibitory effect of LINC00612 on GOLPH3 expression. CONCLUSION: PSB attenuates 5-FU chemoresistance in colon adenocarcinoma by regulating the LINC00612/miRNA-590-3p/GOLPH3 axis.

Anterior segment optical coherence tomography for superficial keratectomy.

PURPOSE: To report the use of anterior segment optical coherence tomography (AS-OCT) for superficial keratectomy (SK) in anterior corneal opacity. METHODS: The characteristics of 43 eyes (39 patients) with various lesions responsible for anterior corneal opacity were included in this retrospective non-comparative study. AS-OCT was performed on all eyes before surgery. The thickness of corneal opacity and the underlying healthy stroma were measured. SK was performed on each individual. RESULTS: Four types of anterior corneal opacity were evaluated, including corneal degeneration (26/43), Reis-Bücklers corneal dystrophy (8/43), alkali burn (1/43) and corneal tumors (8/43). Based on AS-OCT images, all eyes showed abnormal hyper-reflective signals in the superficial cornea to less than one-third of the normal corneal thickness in the deepest corneal opacity. All 43 eyes underwent an SK procedure. In addition, 1 eye with alkali burns and 7 eyes with corneal tumors were combined with amniotic membrane transplantation. All eyes restored transparency without significant complications. CONCLUSION: AS-OCT is a valuable method for objective preoperative and noninvasive assessments of anterior corneal opacities and is useful for guiding SK.

Preparation, Characterization, and Evaluation of Enzyme Co-Modified Fish Gelatin-Based Antibacterial Derivatives.

Fish gelatin (FG)-based wound dressings exhibit superior water absorption capacity, thermal stability, and gelation properties, which enhance the performance of these dressings. In this study, our objective was to investigate the conditions underlying the enzymatic hydrolysis of FG and subsequent cross-linking to prepare high-performance gels. A two-step enzymatic method of protease-catalyzed hydrolysis followed by glutamine transglutaminase (TGase)-catalyzed cross-linking was used to prepare novel high-performance fish gelatin derivatives with more stable dispersion characteristics than those of natural gelatin derivatives. Compared with conventional TGase cross-linked derivatives, the novel derivatives were characterized by an average pore size of 150 µm and increased water solubility (423.06% to 915.55%), water retention (by 3.6-fold to 43.89%), thermal stability (from 313 °C to 323 °C), and water vapor transmission rate, which reached 486.72 g·m-2·24 h-1. In addition, loading glucose oxidase onto the fish gelatin derivatives increased their antibacterial efficacy to >99% against Escherichia coli and Staphylococcus aureus.

Distributions, interactions, and dynamics of prokaryotes and phages in a hybrid biological wastewater treatment system.

BACKGROUND: Understanding the interactions and dynamics of microbiotas within biological wastewater treatment systems is essential for ensuring their stability and long-term sustainability. In this study, we developed a systematic framework employing multi-omics and Hi-C sequencing to extensively investigate prokaryotic and phage communities within a hybrid biofilm and activated sludge system. RESULTS: We uncovered distinct distribution patterns, metabolic capabilities, and activities of functional prokaryotes through the analysis of 454 reconstructed prokaryotic genomes. Additionally, we reconstructed a phage catalog comprising 18,645 viral operational taxonomic units (vOTUs) with high length and contiguity using hybrid assembly, and a distinct distribution of phages was depicted between activated sludge (AS) and biofilm. Importantly, 1340 host-phage pairs were established using Hi-C and conventional in silico methods, unveiling the host-determined phage prevalence. The majority of predicted hosts were found to be involved in various crucial metabolic processes, highlighting the potential vital roles of phages in influencing substance metabolism within this system. Moreover, auxiliary metabolic genes (AMGs) related to various categories (e.g., carbohydrate degradation, sulfur metabolism, transporter) were predicted. Subsequent activity analysis emphasized their potential ability to mediate host metabolism during infection. We also profiled the temporal dynamics of phages and their associated hosts using 13-month time-series metagenomic data, further demonstrating their tight interactions. Notably, we observed lineage-specific infection patterns, such as potentially host abundance- or phage/host ratio-driven phage population changes. CONCLUSIONS: The insights gained from this research contribute to the growing body of knowledge surrounding interactions and dynamics of host-phage and pave the way for further exploration and potential applications in the field of microbial ecology. Video Abstract.

Metagenomic absolute quantification of antibiotic resistance genes and virulence factor genes-carrying bacterial genomes in anaerobic digesters.

Sewage treatment works have been considered as hotspots for the dissemination of antibiotic resistance genes (ARGs). Anaerobic digestion (AD) has emerged as a promising approach for controlling the spread of ARGs while destroying biomass in sludge. Evaluating the impact of AD on ARG removal relies on the absolute quantification of ARGs. In this study, we quantified the ARG concentrations in both full-scale and lab-scale AD systems using a cellular spike-ins based absolute quantification approach. Results demonstrated that AD effectively removed 68 ± 18 %, 55 ± 12 %, and 57 ± 19 % of total ARGs in semi-continuous AD digesters, with solid retention times of 15, 20, and 25 days, respectively. The removal efficiency of total ARGs increased as the AD process progressed in the batch digesters over 40 days. A significant negative correlation was observed between digestion time and the concentrations of certain ARG types, such as beta-lactam, sulfonamide, and tetracycline. However, certain potential pathogenic antibiotic resistant bacteria (PARB) and multi-resistant high-risk ARGs-carrying populations robustly persisted throughout the AD process, regardless of the operating conditions. This study highlighted the influence of the AD process and its operating parameters on ARG removal, and revealed the broad spectrum and persistence of PARB in AD systems. These findings provided critical insights for the management of microbial hazards.

Upregulation of GOLPH3 mediated by Bisphenol a promotes colorectal cancer proliferation and migration: evidence based on integrated analysis.

Background: The interaction between environmental endocrine-disrupting chemicals, such as Bisphenol A (BPA), and their influence on cancer progression, particularly regarding the GOLPH3 gene in colorectal cancer, remains unclear. Methods: We performed an integrated analysis of transcriptional profiling, clinical data, and bioinformatics analyses utilizing data from the Comparative Toxicogenomics Database and The Cancer Genome Atlas. The study employed ClueGO, Gene Set Enrichment Analysis, and Gene Set Variation Analysis for functional enrichment analysis, alongside experimental assays to examine the effects of BPA exposure on colorectal cancer cell lines, focusing on GOLPH3 expression and its implications for cancer progression. Results: Our findings demonstrated that BPA exposure significantly promoted the progression of colorectal cancer by upregulating GOLPH3, which in turn enhanced the malignant phenotype of colorectal cancer cells. Comparative analysis revealed elevated GOLPH3 protein levels in cancerous tissues versus normal tissues, with single-cell analysis indicating widespread GOLPH3 presence across various cell types in the cancer microenvironment. GOLPH3 was also associated with multiple carcinogenic pathways, including the G2M checkpoint. Furthermore, our investigation into the colorectal cancer microenvironment and genomic mutation signature underscored the oncogenic potential of GOLPH3, exacerbated by BPA exposure. Conclusion: This study provides novel insights into the complex interactions between BPA exposure and GOLPH3 in the context of colorectal cancer, emphasizing the need for heightened awareness and measures to mitigate BPA exposure risks. Our findings advocate for further research to validate these observations in clinical and epidemiological settings and explore potential therapeutic targets within these pathways.