RGS19 activates the MYH9/ß-catenin/c-Myc positive feedback loop in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common fatal cancers worldwide, and the identification of novel treatment targets and prognostic biomarkers is urgently needed because of its unsatisfactory prognosis. Regulator of G-protein signaling 19 (RGS19) is a multifunctional protein that regulates the progression of various cancers. However, the specific function of RGS19 in HCC remains unclear. The expression of RGS19 was determined in clinical HCC samples. Functional and molecular biology experiments involving RGS19 were performed to explore the potential mechanisms of RGS19 in HCC. The results showed that the expression of RGS19 is upregulated in HCC tissues and is significantly associated with poor prognosis in HCC patients. RGS19 promotes the proliferation and metastasis of HCC cells in vitro and in vivo. Mechanistically, RGS19, via its RGS domain, stabilizes the MYH9 protein by directly inhibiting the interaction of MYH9 with STUB1, which has been identified as an E3 ligase of MYH9. Moreover, RGS19 activates ß-catenin/c-Myc signaling via MYH9, and RGS19 is also a transcriptional target gene of c-Myc. A positive feedback loop formed by RGS19, MYH9, and the ß-catenin/c-Myc axis was found in HCC. In conclusion, our research revealed that competition between RGS19 and STUB1 is a critical mechanism of MYH9 regulation and that the RGS19/MYH9/ß-catenin/c-Myc feedback loop may represent a promising strategy for HCC therapy.

Electrocatalytic Nitrate Reduction on Metallic CoNi-Terminated Catalyst with Industrial-Level Current Density in Neutral Medium.

Green ammonia synthesis through electrocatalytic nitrate reduction reaction (eNO3RR) can serve as an effective alternative to the traditional energy-intensive Haber-Bosch process. However, achieving high Faradaic efficiency (FE) at industrially relevant current density in neutral medium poses significant challenges in eNO3RR. Herein, with the guidance of theoretical calculation, a metallic CoNi-terminated catalyst is successfully designed and constructed on copper foam, which achieves an ammonia FE of up to 100% under industrial-level current density and very low overpotential (-0.15 V versus reversible hydrogen electrode) in a neutral medium. Multiple characterization results have confirmed that the maintained metal atom-terminated surface through interaction with copper atoms plays a crucial role in reducing overpotential and achieving high current density. By constructing a homemade gas stripping and absorption device, the complete conversion process for high-purity ammonium nitrate products is demonstrated, displaying the potential for practical application. This work suggests a sustainable and promising process toward directly converting nitrate-containing pollutant solutions into practical nitrogen fertilizers.

Efficacy and Safety of Surgical Peripheral Iridectomy, Goniosynechialysis, and Goniotomy for Advanced Primary Angle-closure Glaucoma without Cataract: One-year Results of a Multicenter Study.

PRCIS: The combination of surgical peripheral iridectomy, goniosynechialysis, and goniotomy is a safe and effective surgical approach for advanced primary angle-closure glaucoma without cataract. PURPOSE: To evaluate the efficacy and safety of surgical peripheral iridectomy (SPI), goniosynechialysis (GSL), and goniotomy (GT) in advanced primary angle-closure glaucoma (PACG) eyes without cataract. PATIENTS AND METHODS: A prospective multicenter observational study was performed for patients who underwent combined SPI, GSL, and GT for advanced PACG without cataract. Patients were assessed before and after the operation. Complete success was defined as achieving intraocular pressure (IOP) between 6-18 mm Hg with at least a 20% reduction compared to baseline, without the use of ocular hypotensive medications or reoperation. Qualified success adopted the same criteria but allowed medication use. Factors associated with surgical success were analyzed using logistic regression. RESULTS: A total of 61 eyes of 50 advanced PACG were included. All participants completed 12 months of follow-up. Thirty-six eyes (59.0%) achieved complete success, and 56 eyes (91.8%) achieved qualified success. Preoperative and postsurgical at 12 months mean IOPs were 29.7±7.7 and 16.1±4.8 mm Hg, respectively. The average number of ocular hypotensive medications decreased from 1.9 to 0.9 over 12 months. The primary complications included IOP spike (n=9), hyphema (n=7), and shallow anterior chamber (n=3). Regression analysis indicated that older age (odds ratio [OR]=1.09; P=0.043) was positively associated with complete success, while a mixed angle closure mechanism (OR=0.17; P=0.036) reduced success rate. CONCLUSIONS: The combination of SPI, GSL, and GT is a safe and effective surgical approach for advanced PACG without cataract. It has great potential as a first-line treatment option for these patients.

Application of deep eutectic solvents on extraction of flavonoids.

Deep eutectic solvents (DESs), as a new type of eco-friendly solvent, have attracted increasing attention on the extraction and separation of flavonoid compounds from various samples, owing to their excellent properties such as biodegradability and ease of handling with very low toxicity. This article provides a status review of the applications of DESs in the extraction of flavonoids, including the introduction of flavonoid compounds, the properties and superiority of DESs, and extraction methods (ultrasonic-assisted extraction, heating reflux extraction, matrix solid-phase dispersion, and solid-phase extraction). Finally, prospects and challenges in the application of DESs on extraction and separation are extensively elucidated and critically reviewed.

An audio-semantic multimodal model for automatic obstructive sleep Apnea-Hypopnea Syndrome classification via multi-feature analysis of snoring sounds.

Introduction: Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS) is a common sleep-related breathing disorder that significantly impacts the daily lives of patients. Currently, the diagnosis of OSAHS relies on various physiological signal monitoring devices, requiring a comprehensive Polysomnography (PSG). However, this invasive diagnostic method faces challenges such as data fluctuation and high costs. To address these challenges, we propose a novel data-driven Audio-Semantic Multi-Modal model for OSAHS severity classification (i.e., ASMM-OSA) based on patient snoring sound characteristics. Methods: In light of the correlation between the acoustic attributes of a patient's snoring patterns and their episodes of breathing disorders, we utilize the patient's sleep audio recordings as an initial screening modality. We analyze the audio features of snoring sounds during the night for subjects suspected of having OSAHS. Audio features were augmented via PubMedBERT to enrich their diversity and detail and subsequently classified for OSAHS severity using XGBoost based on the number of sleep apnea events. Results: Experimental results using the OSAHS dataset from a collaborative university hospital demonstrate that our ASMM-OSA audio-semantic multimodal model achieves a diagnostic level in automatically identifying sleep apnea events and classifying the four-class severity (normal, mild, moderate, and severe) of OSAHS. Discussion: Our proposed model promises new perspectives for non-invasive OSAHS diagnosis, potentially reducing costs and enhancing patient quality of life.

Risk factors and patterns for progression of fellow-eye myopic traction maculopathy: a 3-year retrospective cohort study.

AIMS: To investigate the effect of preretinal tractional structures (PTS) and posterior scleral structures (PSS) on myopic traction maculopathy (MTM) progression. METHODS: This retrospective cohort study included 185 fellow highly myopic eyes of 185 participants who underwent surgery for MTM. PTS included epiretinal membrane, incomplete posterior vitreous detachment and their combination. PSS included posterior staphyloma and dome-shaped macula (DSM). The MTM stage was graded according to the Myopic Traction Maculopathy Staging System. Optical coherence tomography was used to identify MTM progression, defined as an upgrade of MTM. The Kaplan-Meier method with log-rank test was used to assess MTM progression over the 3-year follow-up period. Risk factors for progression were identified using Cox regression analysis. RESULTS: MTM progression was observed in 48 (25.9%) eyes. Three-year progression-free survival (PFS) rates for eyes with PTS, staphyloma and DSM were 53.7%, 58.2% and 90.7%, respectively. Eyes with PTS and staphyloma exhibited lower 3-year PFS rates than those without PTS or staphyloma (P log-rank test =0.002 and <0.001), while eyes with DSM had a higher 3-year PFS rate than eyes without DSM (P log-rank test=0.01). Multivariate Cox regression analysis showed that PTS (HR, 3.23; p<0.001) and staphyloma (HR, 7.91; p<0.001) were associated with MTM progression, whereas DSM (HR, 0.23; p=0.046) was a protective factor. CONCLUSION: Both PTS and PSS play a critical role in the progression of MTM. Addressing these factors can aid in the management of MTM.

Crystal structure of Trichinella spiralis calreticulin and the structural basis of its complement evasion mechanism involving C1q.

Helminths produce calreticulin (CRT) to immunomodulate the host immune system as a survival strategy. However, the structure of helminth-derived CRT and the structural basis of the immune evasion process remains unclarified. Previous study found that the tissue-dwelling helminth Trichinella spiralis produces calreticulin (TsCRT), which binds C1q to inhibit activation of the complement classical pathway. Here, we used x-ray crystallography to resolve the structure of truncated TsCRT (TsCRTΔ), the first structure of helminth-derived CRT. TsCRTΔ was observed to share the same binding region on C1q with IgG based on the structure and molecular docking, which explains the inhibitory effect of TsCRT on C1q-IgG-initiated classical complement activation. Based on the key residues in TsCRTΔ involved in the binding activity to C1q, a 24 amino acid peptide called PTsCRT was constructed that displayed strong C1q-binding activity and inhibited C1q-IgG-initiated classical complement activation. This study is the first to elucidate the structural basis of the role of TsCRT in immune evasion, providing an approach to develop helminth-derived bifunctional peptides as vaccine target to prevent parasite infections or as a therapeutic agent to treat complement-related autoimmune diseases.

Development and Validation of a Nomogram Model to Predict Obstructive Sleep Apnea.

Objectives: Polysomnography was class I test for who was suspected of obstructive sleep apnea (OSA) which would cost lots of time and money. This study aimed to develop a nomogram model mainly based on oxygen and blood routine indicators to predict OSA. Methods: We retrospectively analyzed 685 patients with suspected OSA at our hospital. Multivariate analysis was used to construct a nomogram. The performance of the nomogram was assessed using calibration and discrimination. Results: The multivariate analysis identified age, gender, body mass index, mean pulse oxygen saturation, percent nighttime with oxygen saturation less than 90%, red blood cell, hematocrit, and red blood cell distribution width SD as significant factors (P < .05). A nomogram was created for the prediction of OSA using these clinical parameters and was internally validated using a bootstrapping method. Our nomogram model showed good discrimination and calibration in terms of predicting OSA, and had a C-index of 0.935 [95% confidence interval (CI), 0.917-0.954] according to the internal validation. Discrimination and calibration in the validation group were also good (C-index, 0.957; 95% CI, 0.930-0.984). Conclusion: The newly developed nomogram can effectively help physicians make better clinical decisions, which may save a lot of time and costs.

Naps and cardiovascular disease risk in different age and sex groups: evidence from a large community cohort.

STUDY OBJECTIVES: This study examined the relationship between naps and cardiovascular disease (CVD) events or death in different age and sex groups. METHODS: A total of 3069 participants stratified by age (<65, 65-74, and ≥75 years old) and sex, underwent Cox regression analysis to assess nap's impact on CVD risk. Restricted cubic spline plots (RCS) were used for dose-response relationships. RESULTS: Significant age-stratified interactions were found when exploring the associations between nap frequency or duration and CVD events (P interaction = 0.001, 0.036 respectively). Individuals younger than 65 years with higher nap frequency or longer nap duration had a significantly increased risk of CVD events (P < 0.001, P = 0.001 respectively). The age group of 65-74 years showed significant associations between CVD events and nap frequency or nap duration (P = 0.017, 0.016 respectively), together with nap duration and CVD deaths (P = 0.008). In the subgroup of females aged 65-74, significant associations were found between nap frequency or duration and CVD events (P = 0.006, 0.002 respectively). Nap frequency or duration was also significantly associated with CVD deaths (P =0.005, 0.010 respectively). CONCLUSIONS: This study underscores a noteworthy correlation between a higher frequency or longer duration of daytime nap and an increased susceptibility to CVD among individuals aged 65-74 years, particularly in females. However, further research is needed to better understand the underlying mechanisms.

FSP1-mediated ferroptosis in cancer: from mechanisms to therapeutic applications.

Ferroptosis is a new discovered regulated cell death triggered by the ferrous ion (Fe2+)-dependent accumulation of lipid peroxides associated with cancer and many other diseases. The mechanism of ferroptosis includes oxidation systems (such as enzymatic oxidation and free radical oxidation) and antioxidant systems (such as GSH/GPX4, CoQ10/FSP1, BH4/GCH1 and VKORC1L1/VK). Among them, ferroptosis suppressor protein 1 (FSP1), as a crucial regulatory factor in the antioxidant system, has shown a crucial role in ferroptosis. FSP1 has been well validated to ferroptosis in three ways, and a variety of intracellular factors and drug molecules can alleviate ferroptosis via FSP1, which has been demonstrated to alter the sensitivity and effectiveness of cancer therapies, including chemotherapy, radiotherapy, targeted therapy and immunotherapy. This review aims to provide important frameworks that, bring the regulation of FSP1 mediated ferroptosis into cancer therapies on the basis of existing studies.

Establishment and clinical application of the HLA genotype database of platelet-apheresis donors in Suzhou.

The establishment of a platelet-apheresis donor database may provide a feasible solution to improve the efficacy of platelet transfusion in patients with immune platelet transfusion refractoriness (PTR). This study aimed to establish HLA genotype database in Suzhou, to provide HLA-I compatible platelets for PTR patients to ensure the safety and effectiveness of platelet transfusions. We used a polymerase chain reaction sequence-based typing (PCR-SBT) method to establish the database by performing high-resolution HLA-A, -B, and -C genotyping on 900 platelet-apheresis donors. HLA-I antibody was detected in patients using a Luminex device, and HLA-I gene matching was performed by an HLA-Matchmaker. We found that the highest frequency of the HLA-A allele was A*11:01 (17.06 %), followed by A*24:02 (14.67 %) and A*02:01 (13.61 %). The highest frequency of the HLA-B allele was B*46:01 (9.78 %), followed by B*40:01 (8.39 %) and B*13:02 (33 %). After the detection of platelet antibodies in 74 patients with immune PTR, we found 30 HLA-A antibodies and 48 HLA-B antibodies, and there were a variety of high frequency antibodies whose alleles were low in the donor database, such as HLA-A*68:02, and B*57:01. After avoiding donor-specific antibodies (DSA) matching, 102 of 209 platelet-compatible transfusions were effective, resulting in an effective rate of 48.8 %, which significantly improved the efficacy of platelet transfusion. The establishment of a platelet donor database is of great significance to improve the therapeutic effect of platelet transfusion in patients with hematologic disorder, and save blood resources, and it is also the premise and guarantee of precise platelet transfusion.

Plumbagin Regulates Snail to Inhibit Hepatocellular Carcinoma Epithelial-Mesenchymal Transition in vivo and in vitro.

Background/Aims: Plumbagin (PL) has been shown to effe ctively inhibit autophagy, suppressing invasion and migration of hepatocellular carcinoma (HCC) cells. However, the specific mechanism remains unclear. This study aimed to investigate the effect of PL on tumor growth factor (TGF)-ß-induced epithelial-mesenchymal transition (EMT) in HCC. Methods: Huh-7 cells were cultured, and in vivo models of EMT and HCC-associated lung metastasis were developed through tail vein and in situ injections of tumor cells. In vivo imaging and hematoxylin and eosin staining were used to evaluate HCC modeling and lung metastasis. After PL intervention, the expression levels of Snail, vimentin, E-cadherin, and N-cadherin in the liver were evaluated through immunohistochemistry and Western blot. An in vitro TGF-ß-induced cell EMT model was used to detect Snail, vimentin, E-cadherin, and N-cadherin mRNA levels through a polymerase chain reaction. Their protein levels were detected by immunofluorescence staining and Western blot. Results: In vivo experiments demonstrated that PL significantly reduced the expression of Snail, vimentin, and N-cadherin, while increasing the expression of E-cadherin at the protein levels, effectively inhibiting HCC and lung metastasis. In vitro experiments confirmed that PL up-regulated epithelial cell markers, down-regulated mesenchymal cell markers, and inhibited EMT levels in HCC cells. Conclusion: PL inhibits Snail expression, up-regulates E-cadherin expression, and down-regulates N-cadherin and vimentin expression, preventing EMT in HCC cells and reducing lung metastasis.

Human myiasis in Sub-Saharan Africa: A systematic review.

BACKGROUND: Human myiasis is a parasitic dipteran fly infestation that infects humans and vertebrates worldwide. However, the disease is endemic in Sub-Saharan Africa and Latin America. In Sub-Saharan Africa, it is under-reported and therefore its prevalence is unknown. This systematic review aims to elucidate the prevalence of human myiasis, factors that influence the infection, and myiasis-causing fly species in SSA. The review also dwelled on the common myiasis types and treatment methods of human myiasis. METHODS: Here, we collect cases of human myiasis in Sub-Saharan Africa based on literature retrieved from PubMed, Google Scholar and Science Direct from 1959 to 2022. A total of 75 articles and 157 cases were included in the study. The recommendations of PRISMA 2020 were used for the realization of this systematic review. RESULTS: In total, 157 cases of human myiasis in SSA were reviewed. Eleven fly species (Cordylobia anthropophaga, Cordylobia rodhaini, Dermatobia hominis, Lucilia cuprina, Lucilia sericata, Oestrus ovis, Sarcophaga spp., Sarcophaga nodosa, Chrysomya megacephala, Chrysomya chloropyga and Clogmia albipuntum) were found to cause human myiasis in SSA. Cordylobia anthropophaga was the most prevalent myiasis-causing species of the reported cases (n = 104, 66.2%). More than half of the reported cases were from travelers returning from SSA (n = 122, 77.7%). Cutaneous myiasis was the most common clinical presentation of the disease (n = 86, 54.7%). Females were more infected (n = 78, 49.6%) than males, and there was a higher infestation in adults than young children. CONCLUSION: The findings of this study reveals that international travelers to Sub-Saharan Africa were mostly infested therefore, we recommend that both international travelers and natives of SSA be enlightened by public health officers about the disease and its risk factors at entry points in SSA and the community level respectively. Clinicians in Sub-Saharan Africa often misdiagnose the disease and most of them lack the expertise to properly identify larvae, so we recommend the extensive use of molecular identification methods instead.

Objective sleep characteristics and hypertension: a community-based cohort study.

Objective: The link between sleep quality and hypertension risk is well-established. However, research on the specific dose-relationship between objective sleep characteristics and hypertension incidence remains limited. This study aims to explore the dose-relationship association between objective sleep characteristics and hypertension incidence. Methods: A community-based prospective cohort study design was employed using data from the Sleep Heart Health Study (SHHS). A total of 2,460 individuals were included in the study, of which 780 had hypertension. Baseline personal characteristics and medical history were collected. Objective sleep characteristics were obtained through polysomnography (PSG). Multivariate logistic regression models were utilized for analysis. Restricted cubic splines (RCS) were used to examine dose-relationship associations. Results: After adjusting for covariates, the percentage of total sleep duration in stage 2 (N2%) was positively associated with hypertension incidence, while the N3% was negatively associated with hypertension incidence Odds ratio (OR) = 1.009, 95% confidence interval (CI) [1.001, 1.018], P = 0.037; OR = 0.987, 95% CI: [0.979, 0.995], P = 0.028, respectively. For every 10% increase in N2 sleep, the risk of developing hypertension increases by 9%, while a 3% decrease in N3 sleep corresponds to a 0.1% increase in the incidence of hypertension. In the subgroup of non-depression, a positive association between N2% and hypertension was significant statistically (OR = 1.012, 95%CI, 1.002, 1.021, P = 0.013, Pinteraction = 0.013). RCS demonstrated that the risk of developing hypertension was lower when N2% ranged from 38% to 58% and rapidly increased thereafter (P = 0.002, non-linear P = 0.040). The lowest risk for hypertension incidence risk of N3% occurring at 25%, and a significant increase below 15% or above 40% (P = 0.001, non-linear P = 0.008). Conclusions: There's a negative association between N3% and the incidence of hypertension, and a positive association between N2% and the incidence of hypertension, particularly among non-depression individuals. These associations exhibit strong non-linear dose-response relationships.

Association between gut microbiota and Hirschsprung disease: a bidirectional two-sample Mendelian randomization study.

Background: Several studies have pointed to the critical role of gut microbiota (GM) and their metabolites in Hirschsprung disease (HSCR) pathogenesis. However, the detailed causal relationship between GM and HSCR remains unknown. Methods: In this study, we used two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between GM and HSCR, based on the MiBioGen Consortium's genome-wide association study (GWAS) and the GWAS Catalog's HSCR data. Reverse MR analysis was performed subsequently, and the sensitivity analysis, Cochran's Q-test, MR pleiotropy residual sum, outlier (MR-PRESSO), and the MR-Egger intercept were used to analyze heterogeneity or horizontal pleiotropy. 16S rDNA sequencing and targeted mass spectrometry were developed for initial validation. Results: In the forward MR analysis, inverse-variance weighted (IVW) estimates suggested that Eggerthella (OR: 2.66, 95%CI: 1.23-5.74, p = 0.01) was a risk factor for HSCR, while Peptococcus (OR: 0.37, 95%CI: 0.18-0.73, p = 0.004), Ruminococcus2 (OR: 0.32, 95%CI: 0.11-0.91, p = 0.03), Clostridiaceae1 (OR: 0.22, 95%CI: 0.06-0.78, p = 0.02), Mollicutes RF9 (OR: 0.27, 95%CI: 0.09-0.8, p = 0.02), Ruminococcaceae (OR: 0.16, 95%CI: 0.04-0.66, p = 0.01), and Paraprevotella (OR: 0.45, 95%CI: 0.21-0.98, p = 0.04) were protective factors for HSCR, which had no heterogeneity or horizontal pleiotropy. However, reverse MR analysis showed that HSCR (OR: 1.02, 95%CI: 1-1.03, p = 0.049) is the risk factor for Eggerthella. Furthermore, some of the above microbiota and short-chain fatty acids (SCFAs) were altered in HSCR, showing a correlation. Conclusion: Our analysis established the relationship between specific GM and HSCR, identifying specific bacteria as protective or risk factors. Significant microbiota and SCFAs were altered in HSCR, underlining the importance of further study and providing new insights into the pathogenesis and treatment.

GINS2 regulates temozolomide chemosensitivity via the EGR1/ECT2 axis in gliomas.

Temozolomide (TMZ), a DNA alkylating agent, has become the primary treatment for glioma, the most common malignancy of the central nervous system. Although TMZ-containing regimens produce significant clinical response rates, some patients inevitably suffer from inferior treatment outcomes or disease relapse, likely because of poor chemosensitivity of glioma cells due to a robust DNA damage response (DDR). GINS2, a subunit of DNA helicase, contributes to maintaining genomic stability and is highly expressed in various cancers, promoting their development. Here, we report that GINS2 was upregulated in TMZ-treated glioma cells and co-localized with γH2AX, indicating its participation in TMZ-induced DDR. Furthermore, GINS2 regulated the malignant phenotype and TMZ sensitivity of glioma cells, mostly by promoting DNA damage repair by affecting the mRNA stability of early growth response factor 1 (EGR1), which in turn regulates the transcription of epithelial cell-transforming sequence 2 (ECT2). We constructed a GINS2-EGR1-ECT2 prognostic model, which accurately predicted patient survival. Further, we screened Palbociclib/BIX-02189 which dampens GINS2 expression and synergistically inhibits glioma cell proliferation with TMZ. These findings delineate a novel mechanism by which GINS2 regulates the TMZ sensitivity of glioma cells and propose a promising combination therapy to treat glioma.

Catalytic Asymmetric Difluoroalkylation Using In Situ Generated Difluoroenol Species as the Privileged Synthon.

A robust and practical difluoroalkylation synthon, α,α-difluoroenol species, which generated in situ from trifluoromethyl diazo compounds and water in the presence of dirhodium complex, is disclosed. As compared to the presynthesized difluoroenoxysilane and in situ formed difluoroenolate under basic conditions, this difluoroenol intermediate displayed versatile reactivity, resulting in dramatically improved enantioselectivity under mild conditions. As demonstrated in catalytic asymmetric aldol reaction and Mannich reactions with ketones or imines in the presence of chiral organocatalysts, quinine-derived urea, and chiral phosphoric acid (CPA), respectively, this relay catalysis strategy provides an effective platform for applying asymmetric fluorination chemistry. Moreover, this method features a novel 1,2-difunctionalization process via installation of a carbonyl motif and an alkyl group on two vicinal carbons, which is a complementary protocol to the metal carbene gem-difunctionalization reaction.

Melatonin ameliorates retinal ganglion cell senescence and apoptosis in a SIRT1-dependent manner in an optic nerve injury model.

Melatonin is involved in exerting protective effects in aged-related and neurodegenerative diseases through a silent information regulator type 1 (SIRT1)-dependent pathway. However, little was known about the impact of melatonin on retinal ganglion cell (RGC) senescence and apoptosis following optic nerve crush (ONC). Thus, this study aimed to examine the effects of melatonin on RGC senescence and apoptosis after ONC and investigate the involvement of SIRT1 in this process. To study this, an ONC model was established. EX-527, an inhibitor of SIRT1, was injected intraperitoneally into mice. And melatonin was administrated abdominally into mice after ONC every day. Hematoxylin & eosin staining, retina flat-mounts and optical coherence tomography were used to evaluate the loss of retina cells/neurons. Pattern electroretinogram (p-ERG) was performed to evaluate the function of RGCs. Immunofluorescence and western blot were used to evaluate protein expression. SA-ß-gal staining was employed to detect senescent cells. The results demonstrated that melatonin partially rescued the expression of SIRT1 in RGC 3 days after ONC. Additionally, melatonin administration partly rescued the decreased RGC number and ganglion cell complex thickness observed 14 days after ONC. Melatonin also suppressed ONC-induced senescence and apoptosis index. Furthermore, p-ERG showed that melatonin improved the amplitude of P50, N95 and N95/P50 following ONC. Importantly, the protective effects of melatonin were reversed when EX-527 was administered. In summary, this study revealed that melatonin attenuated RGC senescence and apoptosis through a SIRT1-dependent pathway after ONC. These findings provide valuable insights for the treatment of RGC senescence and apoptosis.

Integrated multi-omics analysis reveals gut microbiota dysbiosis and systemic disturbance in major depressive disorder.

Major depressive disorder (MDD) involves systemic changes in peripheral blood and gut microbiota, but the current understanding is incomplete. Herein, we conducted a multi-omics analysis of fecal and blood samples obtained from an observational cohort including MDD patients (n = 99) and healthy control (HC, n = 50). 16S rRNA sequencing of gut microbiota showed structural alterations in MDD, as characterized by increased Enterococcus. Metagenomics sequencing of gut microbiota showed substantial functional alterations including upregulation in the superpathway of the glyoxylate cycle and fatty acid degradation and downregulation in various metabolic pathways in MDD. Plasma metabolomics revealed decreased amino acids and bile acids, together with increased sphingolipids and cholesterol esters in MDD. Notably, metabolites involved in arginine and proline metabolism were decreased while sphingolipid metabolic pathway were increased. Mass cytometry analysis of blood immune cell subtypes showed rises in proinflammatory immune subsets and declines in anti-inflammatory immune subsets in MDD. Furthermore, our findings revealed disease severity-related factors of MDD. Interestingly, we classified MDD into two immune subtypes that were highly correlated with disease relapse. Moreover, we established discriminative signatures that differentiate MDD from HC. These findings contribute to a comprehensive understanding of the MDD pathogenesis and provide valuable resources for the discovery of biomarkers.

Microbial diversity and their extracellular enzyme activities among different soil particle sizes in mossy biocrust under N limitation in the southeastern Tengger Desert, China.

Introduction: Mossy biocrust represents a stable stage in the succession of biological soil crust in arid and semi-arid areas, providing a microhabitat that maintains microbial diversity. However, the impact of mossy biocrust rhizoid soil and different particle sizes within the mossy biocrust layer and sublayer on microbial diversity and soil enzyme activities remains unclear. Methods: This study utilized Illumina MiSeq sequencing and high-throughput fluorometric technique to assess the differences in microbial diversity and soil extracellular enzymes between mossy biocrust rhizoid soil and different particle sizes within the mossy biocrust sifting and sublayer soil. Results: The results revealed that the total organic carbon (TOC), total nitrogen (TN), ammonium (NH4+) and nitrate (NO3-) in mossy biocrust rhizoid soil were the highest, with significantly higher TOC, TN, and total phosphorus (TP) in mossy biocrust sifting soil than those in mossy biocrust sublayer soil. Extracellular enzyme activities (EAAs) exhibited different responses to various soil particle sizes in mossy biocrust. Biocrust rhizoid soil (BRS) showed higher C-degrading enzyme activity and lower P-degrading enzyme activity, leading to a significant increase in enzyme C: P and N: P ratios. Mossy biocrust soils were all limited by microbial relative nitrogen while pronounced relative nitrogen limitation and microbial maximum relative carbon limitation in BRS. The diversity and richness of the bacterial community in the 0.2 mm mossy biocrust soil (BSS0.2) were notably lower than those in mossy biocrust sublayer, whereas the diversity and richness of the fungal community in the rhizoid soil were significantly higher than those in mossy biocrust sublayer. The predominant bacterial phyla in mossy biocrust were Actinobacteriota, Protebacteria, Chloroflexi, and Acidobacteriota, whereas in BSS0.2, the predominant bacterial phyla were Actinobacteriota, Protebacteria, and Cyanobacteria. Ascomycota and Basidiomycota were dominant phyla in mossy biocrust. The bacterial and fungal community species composition exhibited significant differences. The mean proportions of Actinobacteriota, Protebacteria, Chloroflexi, Acidobacteriota, Acidobacteria, Cyanobacteria, and Bacteroidota varied significantly between mossy biocrust rhizoid and different particle sizes of mossy biocrust sifting and sublayer soil (p < 0.05). Similarly, significant differences (p < 0.05) were observed in the mean proportions of Ascomycota, Basidiomycota, and Glomeromycota between mossy biocrust rhizoid and different particle sizes within the mossy biocrust sifting and sublayer soil. The complexity and connectivity of bacterial and fungal networks were higher in mossy biocrust rhizoid soil compared with different particle sizes within the mossy biocrust sifting and sublayer soil. Discussion: These results offer valuable insights to enhance our understanding of the involvement of mossy biocrust in the biogeochemical cycle of desert ecosystems.