Tuning Electrons Migration of Dual S Defects Mediated MoS2-x/ZnIn2S4-x Toward Highly Efficient Photocatalytic Hydrogen Production.

Photocatalytic hydrogen production is a prevalent method for hydrogen synthesis. However, high recombination rate of photogenerated carriers and high activation energy barrier of H remain persistent challenge. Here, the two-step hydrothermal method is utilized to prepare dual S-defect mediated catalyst molybdenum sulfide/zinc indium sulfide (MSv/ZISv), which has high hydrogen production rate of 8.83 mmol g-1h-1 under simulated sunlight. The achieved rate is 21.91 times higher than pure ZnIn2S4 substrate. Defects in ZIS within MSv/ZISv modify the primitive electronic structure by creating defect state that retaining good reducing power, leading to the rapid separation of electron-hole pairs and the generation of additional photogenerated carriers. The internal electric field further enhances the migration toward to cocatalyst. Simultaneously, the defects introduced on the MoS2 cause electron rearrangement, leading to electron clustering on both S vacancies and edge S. Thereby MSv/ZISv exhibits the lowest activation energy barrier and |ΔGH*|. This work explores the division of synergies between different types of S defects, providing new insights into the coupling of defect engineering.

Near-complete recycling of real mix electroplating sludge as valuable metals via Fe/Cr co-crystallization and stepwise extraction route.

In electroplating sludge, iron (Fe) and aluminum (Al) are common impurities that need to be separated before recycling valuable heavy metals. However, the traditional Fe/Al separation process often leads to significant losses of heavy metals. To address this issue, a new approach was developed to sequentially separate Fe/Al and recycle chromium (Cr) and nickel (Ni) from real electroplating sludge. The sludge contained 4.5% Cr, 1.2% Al, 1.1% Ni, and 14.6% Fe. Initially, the sludge was completely dissolved in a mixture of hydrochloric and nitric acids. The resulting acid solution was then heated to 160 °C for 10 h with the addition of saccharose. This hydrothermal treatment led to the hydrolysis and crystallization of 98.3% of Fe, 31.8% of Cr, 1.1% of Al, and 4.9% of Ni, forming akaganeite-bearing particles. It was observed that the excessive amount of saccharose also improved the removal of Cr, Al, and Ni, but decreased the removal of Fe. After the hydrothermal treatment, the remaining supernatant was adjusted to different pH levels (1.9, 2.9, and 4.5, respectively), and then Al, Cr, and Ni were stepwise extracted using di-(2-ethylhexyl) phosphate acid (P204). The recycling efficiencies achieved were 97.4% for Al, 61.2% for Cr, and 89.3% for Ni. This approach provides a promising method for the stepwise separation of Fe/Al and the recycling of heavy metals from electroplating sludge.

Common Pathophysiological Mechanisms and Treatment of Diabetic Gastroparesis.

Diabetic gastroparesis (DGP) is a common complication of diabetes mellitus, marked by gastrointestinal motility disorder, a delayed gastric emptying present in the absence of mechanical obstruction. Clinical manifestations include postprandial fullness and epigastric discomfort, bloating, nausea, and vomiting. DGP may significantly affect the quality of life and productivity of patients. Research on the relationship between gastrointestinal dynamics and DGP has received much attention because of the increasing prevalence of DGP. Gastrointestinal motility disorders are closely related to a variety of factors including the absence and destruction of interstitial cells of Cajal, abnormalities in the neuro-endocrine system and hormone levels. Therefore, this study will review recent literature on the mechanisms of DGP and gastrointestinal motility disorders as well as the development of prokinetic treatment of gastrointestinal motility disorders in order to give future research directions and identify treatment strategies for DGP.

Discovery of a Potent Dual Son of Sevenless 1 (SOS1) and Epidermal Growth Factor Receptor (EGFR) Inhibitor for the Treatment of Prostate Cancer.

Multitarget medications represent an appealing therapy against the disease with multifactorial abnormalities─cancer. Therefore, simultaneously targeting son of sevenless 1 (SOS1) and epidermal growth factor receptor (EGFR), two aberrantly expressed proteins crucial for the oncogenesis and progression of prostate cancer, may achieve active antitumor effects. Here, we discovered dual SOS1/EGFR-targeting compounds via pharmacophore-based docking screening. The most prominent compound SE-9 exhibited nanomolar inhibition activity against both SOS1 and EGFR and efficiently suppressed the phosphorylation of ERK and AKT in prostate cancer cells PC-3. Cellular assays also revealed that SE-9 displayed strong antiproliferative activities through diverse mechanisms, such as induction of cell apoptosis and G1 phase cell cycle arrest, as well as reduction of angiogenesis and migration. Further in vivo findings showed that SE-9 potently inhibited tumor growth in PC-3 xenografts without obvious toxicity. Overall, SE-9 is a novel dual-targeting SOS1/EGFR inhibitor that represents a promising treatment strategy for prostate cancer.

Design, Synthesis, and Biological Evaluation of ß-Trifluoroethoxydimethyl Selenides as Potent Antiosteoporosis Agents.

An efficient protocol for the synthesis of ß-trifluoroethoxydimethyl selenides was achieved under mild reaction conditions, and 39 compounds were prepared. All compounds were evaluated for their abilities to inhibit RANKL-induced osteoclastogenesis, compound 4aa exhibited the most potent activity. Further investigations revealed that 4aa could inhibit F-actin ring generation, bone resorption, and osteoclast-specific gene expression in vitro. Western blot analyses demonstrated that compound 4aa abrogated the RANKL-induced mitogen-activated protein kinase and NF-kB-signaling pathways. In addition, 4aa also displayed a notable impact on the osteoblastogenesis of MC3T3-E1 preosteoblasts. In vivo experiments revealed that compound 4aa significantly ameliorated bone loss in an ovariectomized (OVX) mice model. Furthermore, the surface plasmon resonance experiment results revealed that 4aa probably bound to RANKL. Collectively, the above-mentioned findings suggested that compound 4aa as a potential RANKL inhibitor averted OVX-triggered osteoporosis by regulating the inhibition of osteoclast differentiation and stimulation of osteoblast differentiation.

A novel natural Syk inhibitor suppresses IgE-mediated mast cell activation and passive cutaneous anaphylaxis.

Spleen tyrosine kinase (Syk) plays a crucial role as a target for allergy treatment due to its involvement in immunoreceptor signaling. The purpose of this study was to identify natural inhibitors of Syk and assess their effects on the IgE-mediated allergic response in mast cells and ICR mice. A list of eight compounds was selected based on pharmacophore and molecular docking, showing potential inhibitory effects through virtual screening. Among these compounds, sophoraflavanone G (SFG) was found to inhibit Syk activity in an enzymatic assay, with an IC50 value of 2.2 µM. To investigate the conformational dynamics of the SYK-SFG system, we performed molecular dynamics simulations. The stability of the binding between SFG and Syk was evaluated using root mean square deviation (RMSD) and root mean square fluctuation (RMSF). In RBL-2H3 cells, SFG demonstrated a dose-dependent suppression of IgE/BSA-induced mast cell degranulation, with no significant cytotoxicity observed at concentrations below 10.0 µM within 24 h. Furthermore, SFG reduced the production of TNF-α and IL-4 in RBL-2H3 cells. Mechanistic investigations revealed that SFG inhibited downstream signaling proteins, including phospholipase Cγ1 (PLCγ1), as well as mitogen-activated protein kinases (AKT, Erk1/2, p38, and JNK), in mast cells in a dose-dependent manner. Passive cutaneous anaphylaxis (PCA) experiments demonstrated that SFG could reduce ear swelling, mast cell degranulation, and the expression of COX-2 and IL-4. Overall, our findings identify naturally occurring SFG as a direct inhibitor of Syk that effectively suppresses mast cell degranulation both in vitro and in vivo.

Functional prediction of the potential NGLY1 mutations associated with rare disease CDG.

Genetic diseases are currently diagnosed by functional mutations. However, only some mutations are associated with disease. It is necessary to establish a quick prediction model for clinical screening. Pathogenic mutations in NGLY1 cause a rare autosomal recessive disease known as congenital disorder of deglycosylation (NGLY1-CDDG). Although NGLY1-CDDG can be diagnosed through gene sequencing, clinical relevance of a detected mutation in NGLY1 needs to be further confirmed. In this study, taken NGLY1-CDDG as an example, a comprehensive and practical predictive model for pathogenic mutations on NGLY1 through an NGLY1/Glycopeptide complex model was constructed, the binding sites of NGLY1 and glycopeptides were simulated, and an in vitro enzymatic assay system was established to facilitate quick clinical decisions for NGLY1-CDDG patients. The docking model covers 42 % of reported NGLY1-CDDG missense mutations (5/12). All reported mutations were subjected to in vitro enzymatic assay in which 18 mutations were dysfunctional (18/30). In addition, a full spectrum of functional R328 mutations was assayed and 11 mutations were dysfunctional (11/19). In this study, a model of NGLY1 and glycopeptides was built for potential functional mutations in NGLY1. In addition, the effect of potential regulatory compounds, including N-acetyl-l-cysteine and dithiothreitol, on NGLY1 was examined. The established in vitro assay may serve as a standard protocol to facilitate rapid diagnosis of all mutations in NGLY1-CDDG. This method could also be applied as a comprehensive and practical predictive model for the other rare genetic diseases.

Precision of liver and pancreas apparent diffusion coefficients using motion-compensated gradient waveforms in DWI.

BACKGROUND: Diffusion weighted imaging (DWI) with optimized motion-compensated gradient waveforms reduces signal dropouts in the liver and pancreas caused by cardiovascular-associated motion, however its precision is unknown. We hypothesized that DWI with motion-compensated DW gradient waveforms would improve apparent diffusion coefficient (ADC)-repeatability and inter-reader reproducibility compared to conventional DWI in these organs. METHODS: In this IRB-approved, prospective, single center study, subjects recruited between October 2019 and March 2020 were scanned twice on a 3 T scanner, with repositioning between test and retest. Each scan included two respiratory-triggered DWI series with comparable acquisition time: 1) conventional (monopolar) 2) motion- compensated diffusion gradients. Three readers measured ADC values. One-way ANOVA, Bland-Altman analysis were used for statistical analysis. RESULTS: Eight healthy participants (4 male/4 female), with a mean age of 29 ±â€¯4 years, underwent the liver and pancreas MRI protocol. Four patients with liver metastases (2 male/2 female) with a mean age of 58 ±â€¯5 years underwent the liver MRI protocol. In healthy participants, motion-compensated DWI outperformed conventional DWI with mean repeatability coefficient of 0.14 × 10-3 (CI:0.12-0.17) vs. 0.31 × 10-3 (CI:0.27-0.37) mm2/s for liver, and 0.11 × 10-3 (CI:0.08-0.15) vs. 0.34 × 10-3 (CI:0.27-0.49) mm2/s for pancreas; and with mean reproducibility coefficient of 0.20 × 10-3 (CI:0.18-0.23) vs. 0.51 × 10-3 (CI:0.46-0.58) mm2/s for liver, and 0.16 × 10-3 (CI:0.13-0.20) vs. 0.42 × 10-3 (CI:0.34-0.52) mm2/s for pancreas. In patients, improved repeatability was observed for motion-compensated DWI in comparison to conventional with repeatability coefficient of 0.51 × 10- 3 mm2/s (CI:0.35-0.89) vs. 0.70 × 10-3 mm2/s (CI:0.49-1.20). CONCLUSION: Motion-compensated DWI enhances the precision of ADC measurements in the liver and pancreas compared to conventional DWI.

Network Pharmacology, Molecular Docking Analysis and Molecular Dynamics Simulation of Scutellaria baicalensis in the Treatment of Liver Fibrosis.

BACKGROUND: Traditional Chinese medicine Scutellaria Baicalensis (SB), one of the clinical firstline heat-clearing drugs, has obvious symptomatic advantages for hepatic fibrosis with dampness-heat stasis as its syndrome. We aim to predict and validate the potential mechanism of Scutellaria baicalensis active ingredients against liver fibrosis more scientifically and effectively. METHODS: The underlying mechanism of Scutellaria baicalensis in inhibiting hepatic fibrosis was studied by applying network pharmacology, molecular docking and molecular dynamics simulation. Expression levels of markers in activated Hepatic Stellate Cells (HSC) after administration of three Scutellaria baicalensis extracts were determined by Western blot and Real-time PCR, respectively, in order to verify the anti-fibrosis effect of the active ingredients Results: There are 164 common targets of drugs and diseases screened and 115 signaling pathways obtained, which were mainly associated with protein phosphorylation, senescence and negative regulation of the apoptotic process. Western blot and Real-time PCR showed that Scutellaria baicalensis extracts could reduce the expression of HSC activation markers, and Oroxylin A had the strongest inhibitory effect on it. Molecular docking results showed that Oroxylin A had high binding activity to target proteins. Molecular dynamics simulation demonstrates promising stability of the Oroxylin A-AKT1 complex over the simulated MD time of 200 ns. CONCLUSION: Scutellaria baicalensis active ingredients may inhibit HSC proliferation, reduce the generation of pro-inflammatory factors and block the anti-inflammatory effect of inflammatory signal transduction by inducing HSC apoptosis and senescence, thus achieving the effect of anti-fibrosis.

Status and predictors of readiness for hospital discharge in women with caesarean section: A latent profile analysis.

BACKGROUND: Women undergoing caesarean section (CS) experience difficulties when preparing for discharge, and readiness for hospital discharge (RHD) may depend on individual characteristics. OBJECTIVE: To explore the status of RHD in women with CS, identify the latent classes of RHD, and analyse predictors from a bio-psycho-social perspective. METHODS: A sample of 410 women with CS completed the following questionnaires on demographic and obstetric characteristics: Readiness for Hospital Discharge Study-New Mother Form (RHDS-NMF), Parents' Postnatal Sense of Security (PPSS), Quality of Discharge Teaching Scale (OB-QDTS), and Postpartum Support Questionnaire (PSQ). Latent profile analysis was used to identify the latent classes of RHD. Multiple logistic regression analysis was used to analyse the predictors. RESULTS: In total, 96.6 % of women with CS reported discharge ready, and the score of RHDS-NMF was 136.09 ± 25.59. Three latent classes were identified as Low RHD (16.1 %), Moderate RHD (41.7 %), and High RHD (42.2 %). Primiparas (OR = 2.867 / 1.773; P = 0.012 / 0.033), emergency CS (OR = 3.134 / 2.470; P = 0.006 / 0.002), lower levels of PPSS (OR = 0.909 / 0.942; P = 0.009 / 0.013) and OB-ODTS (OR = 0.948 / 0.975; P < 0.001) were associated with Moderate and Low RHD. Lower PSQ predicted a higher probability of Low RHD (OR = 0.955; P = 0.038). CONCLUSIONS: The perception of RHD by women in the study was inaccurate, with more than half not being classified as High RHD. Healthcare professionals can anticipate interventions for maternal well-being based on the characteristics of the different RHD classes.

Selection of the Dominant Endophytes Based on Illumina Sequencing Analysis for Controlling Bacterial Wilt of Patchouli Caused by Ralstonia solanacearum.

Bacterial wilt caused by Ralstonia solanacearum (RS) is one of the most devastating diseases in patchouli (Pogostemon cablin [Blanco] Benth.), which results in low yield and quality of patchouli. However, no stable and effective control methods have been developed yet. To evaluate the potential of dominant bacterial endophytes in biocontrol, the endophytic bacterial diversity of patchouli was investigated based on Illumina sequencing analysis, and the ability of isolates belonging to the dominant bacterial genera to control RS wilt of patchouli was explored in pot experiments. A total of 245 bacterial genera were detected in patchouli plants, with the highest relative abundance of operational taxonomic units belonging to the genus Pseudomonas detected in roots, leaves, and stems. The Pseudomonas isolates S02, S09, and S26 showed antagonistic activity against RS in vitro and displayed many plant growth-promoting characteristics, including production of indole-3-acetic acid, siderophores, and 1-aminocyclopropane-1-carboxylic acid deaminase and phosphate- and potassium-solubilizing capability. Inoculation of patchouli plants with the isolates S02, S09, and S26 significantly improved shoot growth and decreased the incidence of bacterial wilt caused by RS. The results suggest that screening of dominant bacterial endophytes for effective biocontrol agents based on Illumina sequencing analysis is more efficient than random isolation and screening procedures.

Empagliflozin in children with glycogen storage disease-associated inflammatory bowel disease: a prospective, single-arm, open-label clinical trial.

Glycogen storage disease type Ib (GSD-Ib) is a rare inborn error of glycogen metabolism caused by mutations in SLC37A4. Patients with GSD-Ib are at high risk of developing inflammatory bowel disease (IBD). We evaluated the efficacy of empagliflozin, a renal sodium‒glucose cotransporter protein 2 (SGLT2) inhibitor, on colonic mucosal healing in patients with GSD-associated IBD. A prospective, single-arm, open-label clinical trial enrolled eight patients with GSD-associated IBD from Guangdong Provincial People's Hospital in China from July 1, 2022 through December 31, 2023. Eight patients were enrolled with a mean age of 10.34 ± 2.61 years. Four male and four female. The endoscopic features included deep and large circular ulcers, inflammatory hyperplasia, obstruction and stenosis. The SES-CD score significantly decreased at week 48 compared with before empagliflozin. Six patients completed 48 weeks of empagliflozin therapy and endoscopy showed significant improvement or healing of mucosal ulcers, inflammatory hyperplasia, stenosis, and obstruction. One patient had severe sweating that required rehydration and developed a urinary tract infection. No serious or life-threatening adverse events. This study suggested that empagliflozin may promote colonic mucosal healing and reduce hyperplasia, stenosis, and obstruction in children with GSD-associated IBD.

Co-expression of immune checkpoints in glioblastoma revealed by single-nucleus RNA sequencing and spatial transcriptomics.

Glioblastoma (GBM) is one of the most malignant tumors of the central nervous system. The pattern of immune checkpoint expression in GBM remains largely unknown. We performed snRNA-Seq and spatial transcriptomic (ST) analyses on untreated GBM samples. 8 major cell types were found in both tumor and adjacent normal tissues, with variations in infiltration grade. Neoplastic cells_6 was identified in malignant cells with high expression of invasion and proliferator-related genes, and analyzed its interactions with microglia, MDM cells and T cells. Significant alterations in ligand-receptor interactions were observed, particularly between Neoplastic cells_6 and microglia, and found prominent expression of VISTA/VSIG3, suggesting a potential mechanism for evading immune system attacks. High expression of TIM-3, VISTA, PSGL-1 and VSIG-3 with similar expression patterns in GBM, may have potential as therapeutic targets. The prognostic value of VISTA expression was cross-validated in 180 glioma patients, and it was observed that patients with high VISTA expression had a poorer prognosis. In addition, multimodal cross analysis integrated SnRNA-seq and ST, revealing complex intracellular communication and mapping the GBM tumor microenvironment. This study reveals novel molecular characteristics of GBM, co-expression of immune checkpoints, and potential therapeutic targets, contributing to improving the understanding and treatment of GBM.

The impact of job stress on perceived professional benefits among Chinese nurses caring for patients with gynecological cancer: mediating effects of perceived social support and self-efficacy.

Introduction: Nurses caring for patients with gynecological cancer experience significant job stress, which adversely impacts their mental health. Previous studies have indicated that perceived professional benefits serves as a protective factor for nurses' mental health, and factors such as job stress, perceived social support and self-efficacy influence their perceived professional benefits. However, the relationships between these factors and the associated mechanisms have remained incompletely understood. This study explored the role of perceived social support and self-efficacy in job stress and perceived professional benefits among nurses caring for patients with gynecological cancer. Methods: During June and July 2023, an investigation was conducted in Anhui Province. The Nurse Job Stressors Scale, Perceived Social Support Scale, Nurses' Perceived Professional Benefits Questionnaire and General Self-Efficacy Scale were administered to 311 nurses caring for patients with gynecological cancer. A chained-mediated effect model was constructed and validated. Results: Job stress negatively affected nurses' perceived professional benefits. Perceived social support was a mediator in job stress and nurses' perceived professional benefits, with a mediating effect value of -0.093. Additionally, perceived social support and self-efficacy functioned as sequential mediators in this relationship, with a mediating effect value of -0.032. Conclusion: This study unveils the influencing mechanisms of job stress on perceived professional benefits of nurses caring for patients with gynecological cancer. It is essential for nursing managers to alleviate nurses' job stress, provide sufficient and effective social support and improve their self-efficacy, ultimately enhancing their perceived professional benefits.

Cetyltrimethylammonium Bromide-Modified Laponite@Diatomite Composites for Enhanced Adsorption Performance of Organic Pollutants.

This work aims to enhance the adsorption performance of Laponite @diatomite for organic pollutants by modifying it with cetyltrimethylammonium bromide (CTAB). The microstructure and morphology of the CTAB-modified Laponite @diatomite material were characterized using SEM, XRD, FTIR, BET, and TG. Furthermore, the influences of key parameters, containing pH, adsorbent dosage, reaction time, and reaction temperature, on the adsorption process were investigated. The kinetics, thermodynamics, and isotherm models of the adsorption process were analyzed. Finally, potential adsorption mechanisms were given based on the characterization. The research findings indicate that CTAB-La@D exhibits good adsorption performance toward Congo red (CR) over a broad pH range. The maximum adsorption capacity of CR was 451.1 mg/g under the optimum conditions (dosage = 10 mg, contact time = 240 min, initial CR concentration = 100 mg/L, temperature = 25 °C, and pH = 7). The adsorption process conformed to the pseudo-second-order kinetic model, and the adsorption isotherms indicated that the adsorption process of CR was more in line with the Langmuir model, and it was physical adsorption. Thermodynamic analysis illustrates that the adsorption process is exothermic and spontaneous. Additionally, the mechanisms of electrostatic adsorption and hydrophobic effect adsorption of CR were investigated through XPS and FTIR analysis. This work provides an effective pathway for designing high-performance adsorbents for the removal of organic dye, and the synthesized materials hold great capability for practical utilization in the treatment of wastewater.

Activation of the BMP2-SMAD1-CGRP pathway in dorsal root ganglia contributes to bone cancer pain in a rat model.

Peripheral nerve remodeling and sensitization are involved in cancer-related bone pain. As a member of the transforming growth factor-ß class, bone morphogenetic protein 2 (BMP2) is recognized to have a role in the development of the neurological and skeletal systems. Our previous work showed that BMP2 is critical for bone cancer pain (BCP) sensitization. However, the mechanism remains unknown. In the current study, we demonstrated a substantial increase in BMP2 expression in the dorsal root ganglia (DRG) in a rat model of BCP. Knockdown of BMP2 expression ameliorated BCP in rats. Furthermore, the DRG neurons of rats with BCP expressed higher levels of calcitonin gene-related peptide (CGRP), and BCP was successfully suppressed by intrathecal injection of a CGRP receptor blocker (CGRP8-37). Downregulation of BMP2 expression reduced the expression of CGRP in the DRG of rats with BCP and relieved pain behavior. Moreover, we revealed that upregulation of CGRP expression in the DRG may be induced by activation of the BMPR/Smad1 signaling pathway. These findings suggest that BMP2 contributes to BCP by upregulating CGRP in DRG neurons via activating BMPR/Smad1 signaling pathway and that therapeutic targeting of the BMP2-Smad1-CGRP pathway may ameliorate BCP in the context of advanced cancer.

Human umbilical cord mesenchymal stem cell therapy for renal dysfunction in Alport syndrome: protocol for an open-label, single-arm trial in China.

INTRODUCTION: Alport syndrome (AS) is one of the most common fatal hereditary renal diseases in human, with a high risk of progressing to end-stage renal disease without effective treatments. Mesenchymal stem cells (MSCs) have recently emerged as a promising therapeutic strategy for chronic kidney disease. However, the safety and therapeutic potential of MSC transfusion for patients with AS are still need to be confirmed. Therefore, we have designed a clinical trial to evaluate the hypothesis that intravenous infusion of human umbilical cord-derived MSC (hUC-MSC) is safe, feasible, and well-tolerated in children with AS. METHODS AND ANALYSIS: We report the protocol of the first prospective, open-label, single-arm clinical trial to evaluate the safety and preliminary efficacy of hUC-MSC transfusion in children with early-stage AS. Paediatric patients diagnosed with AS who have persistent albuminuria will be candidates for screening. Twelve eligible patients are planned to recruit and will receive hUC-MSC infusions under close safety monitoring, and complete the efficacy assessments at scheduled follow-up visits. The primary endpoints include the occurrence of adverse events to assess safety and the albuminuria level for efficacy evaluation. Secondary endpoint assessments are based on haematuria and glomerular filtration measurements. Each patient's efficacy endpoints will be evaluated against their baseline levels. Additionally, the underlying mechanism of hUC-MSC therapy will be explored through transcriptomic and proteomic analysis of blood and urine samples. ETHICS AND DISSEMINATION: The protocol (V.1.0, date 17 January 2015) was approved by the institutional review board of the Affiliated Taihe Hospital of Hubei University of Medicine (ethical approval 03 March 2015). Written informed consent will be obtained from the patient and/or guardians before study specific process. In addition to publication in a peer-reviewed scientific journal, a lay summary of study will be available for participants and the public on the Chinese Organization for Rare Disorders website (http://www.cord.org.cn/). TRIAL REGISTRATION NUMBER: ISRCTN62094626.

Prospective Investigation of Optical Genome Mapping for Prenatal Genetic Diagnosis.

BACKGROUND: Optical genome mapping (OGM) is a novel assay for detecting structural variants (SVs) and has been retrospectively evaluated for its performance. However, its prospective evaluation in prenatal diagnosis remains unreported. This study aimed to prospectively assess the technical concordance of OGM with standard of care (SOC) testing in prenatal diagnosis. METHODS: A prospective cohort of 204 pregnant women was enrolled in this study. Amniotic fluid samples from these women were subjected to OGM and SOC testing, which included chromosomal microarray analysis (CMA) and karyotyping (KT) in parallel. The diagnostic yield of OGM was evaluated, and the technical concordance between OGM and SOC testing was assessed. RESULTS: OGM successfully analyzed 204 cultured amniocyte samples, even with a cell count as low as 0.24 million. In total, 60 reportable SVs were identified through combined OGM and SOC testing, with 22 SVs detected by all 3 techniques. The diagnostic yield for OGM, CMA, and KT was 25% (51/204), 22.06% (45/204), and 18.14% (37/204), respectively. The highest diagnostic yield (29.41%, 60/204) was achieved when OGM and KT were used together. OGM demonstrated a concordance of 95.56% with CMA and 75.68% with KT in this cohort study. CONCLUSIONS: Our findings suggest that OGM can be effectively applied in prenatal diagnosis using cultured amniocytes and exhibits high concordance with SOC testing. The combined use of OGM and KT appears to yield the most promising diagnostic outcomes.

Diagnosis of pulmonary Scedosporium apiospermum infection from bronchoalveolar lavage fluid by metagenomic next-generation sequencing in an immunocompetent female patient with normal lung structure: a case report and literature review.

BACKGROUND: Scedosporium apiospermum (S. apiospermum) belongs to the asexual form of Pseudallescheria boydii and is widely distributed in various environments. S. apiospermum is the most common cause of pulmonary infection; however, invasive diseases are usually limited to patients with immunodeficiency. CASE PRESENTATION: A 54-year-old Chinese non-smoker female patient with normal lung structure and function was diagnosed with pulmonary S. apiospermum infection by metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF). The patient was admitted to the hospital after experiencing intermittent right chest pain for 8 months. Chest computed tomography revealed a thick-walled cavity in the upper lobe of the right lung with mild soft tissue enhancement. S. apiospermum was detected by the mNGS of BALF, and DNA sequencing reads were 426. Following treatment with voriconazole (300 mg q12h d1; 200 mg q12h d2-d20), there was no improvement in chest imaging, and a thoracoscopic right upper lobectomy was performed. Postoperative pathological results observed silver staining and PAS-positive oval spores in the alveolar septum, bronchiolar wall, and alveolar cavity, and fungal infection was considered. The patient's symptoms improved; the patient continued voriconazole for 2 months after surgery. No signs of radiological progression or recurrence were observed at the 10-month postoperative follow-up. CONCLUSION: This case report indicates that S. apiospermum infection can occur in immunocompetent individuals and that the mNGS of BALF can assist in its diagnosis and treatment. Additionally, the combined therapy of antifungal drugs and surgery exhibits a potent effect on the disease.

FUT8-mediated aberrant N-glycosylation of SEMA7A promotes head and neck squamous cell carcinoma progression.

SEMA7A belongs to the Semaphorin family and is involved in the oncogenesis and tumor progression. Aberrant glycosylation has been intricately linked with immune escape and tumor growth. SEMA7A is a highly glycosylated protein with five glycosylated sites. The underlying mechanisms of SEMA7A glycosylation and its contribution to immunosuppression and tumorigenesis are unclear. Here, we identify overexpression and aberrant N-glycosylation of SEMA7A in head and neck squamous cell carcinoma, and elucidate fucosyltransferase FUT8 catalyzes aberrant core fucosylation in SEMA7A at N-linked oligosaccharides (Asn 105, 157, 258, 330, and 602) via a direct protein‒protein interaction. A glycosylated statue of SEMA7A is necessary for its intra-cellular trafficking from the cytoplasm to the cytomembrane. Cytokine EGF triggers SEMA7A N-glycosylation through increasing the binding affinity of SEMA7A toward FUT8, whereas TGF-ß1 promotes abnormal glycosylation of SEMA7A via induction of epithelial-mesenchymal transition. Aberrant N-glycosylation of SEMA7A leads to the differentiation of CD8+ T cells along a trajectory toward an exhausted state, thus shaping an immunosuppressive microenvironment and being resistant immunogenic cell death. Deglycosylation of SEMA7A significantly improves the clinical outcome of EGFR-targeted and anti-PD-L1-based immunotherapy. Finally, we also define RBM4, a splice regulator, as a downstream effector of glycosylated SEMA7A and a pivotal mediator of PD-L1 alternative splicing. These findings suggest that targeting FUT8-SEMA7A axis might be a promising strategy for improving antitumor responses in head and neck squamous cell carcinoma patients.