ReaxFF-Based Molecular Dynamics Study of the Mechanism of the Reaction of N2O4 with H2O.

During long-term storage of the liquid propellant N2O4, it absorbs H2O to form the N2O4(H2O)n system, and this in turn generates HNO3, HNO2, and other substances in the storage tank because of corrosion, which seriously affects the performance of weaponry. In this work, we carried out computational simulations of N2O4 with different masses of water based on ReaxFF, analyzed the reaction intermediates and products, and investigated the mechanism of the reaction of N2O4 with H2O and of N2O4(H2O)n. The results show that the reaction product ω(HNO3+HNO2) undergoes a rapid growth in the early stage of the reaction and then tends toward dynamic equilibrium; the potential energy of the system decreases with the increase of ω(H2O), the reaction rate increases, and the rate of decomposition of HNO2 to form HNO3 increases. When ω(H2O) is 0.2 or 1.0%, the intermediate products are N2O4H2O or N2O4(H2O)2, respectively, and the reaction proceeds along two paths; when ω(H2O) ≥ 2.0%, N2O4(H2O)3 appears as the intermediate product, HNO3 and HNO2 are directly produced in one step, and a stable current loop can be formed within the whole system.

Rapid in-situ aerobic biodegradation of high salt and oily food waste employing constructed synthetic microbiome.

The high salt content of food waste (FW) severely limits microbial physiological activity and reduces its biodegradability. In this study, a salt-tolerant thermophilic bacterial agent that consists of four different substrate degradation functional strains was evaluated for efficient high salt and oily FW in solid-state aerobic biodegradation disposers. The phy-chemical properties, enzyme activities, microbial community structure, and function during the biodegradation process were evaluated under high salt (5%) stress. The results showed that the agent promoted the degradation rate, increased the matrix temperature, decreased the moisture content (MC), and enhanced enzyme activities without putrid smell. High-throughput sequencing indicated community structure succession between different groups and the positive contribution of the inoculated functional strains. During the FW biodegradation process, the Bacillus sp. inoculated was the dominant genus in the agent group. Furthermore, CCA further confirmed the positive effects of the four inoculated strains on high salt and oily FW aerobic biodegradation. Functional prediction and metabolite results both confirmed that the agent was more efficient in carbon, amino acid, and lipid metabolism, which demonstrated that the synthetic microbial consortium holds a potential advantage for efficiency and subsequent resource utilization for organic fertilizer.

The predictive value of next generation sequencing for matching advanced hepatocellular carcinoma patients to targeted and immunotherapy.

Background: Targeted and Immunotherapy has emerged as a new first-line treatment for advanced hepatocellular carcinoma (aHCC). To identify the appropriate targeted and immunotherapy, we implemented next generation sequencing (NGS) to provide predictive and prognostic values for aHCC patients. Methods: Pretreatment samples from 127 HCC patients were examined for genomic changes using 680-gene NGS, and PD-L1 expression was detected by immunohistochemistry. Demographic and treatment data were included for analyses of links among treatment outcomes, drug responses, and genetic profiles. A prognostic index model for predicting benefit from treatment was constructed, taking into account of biomarkers, including TP53, TERT, PD-L1, and tumor mutation burden (TMB) as possible independent prognostic factors. Results: The multivariate Cox regression analyses showed that PD-L1≥1% (HR 25.07, 95%CI 1.56 - 403.29, p=0.023), TMB≥5Mb (HR 86.67, 95% CI 4.00 - 1876.48, p=0.004), TERT MU (HR 84.09, 95% CI 5.23 - 1352.70, p=0.002) and TP53 WT (HR 0.01, 95%CI 0.00 - 0.47, p=0.022) were independent risk factors for overall survival (OS), even after adjusting for various confounders. A prognostic nomogram for OS was developed, with an area under the ROC curve of 0.91, 0.85, and 0.98 at 1-, 2-, and 3- year, respectively, and a prognostic index cutoff of 1.2. According to the cutoff value, the patients were divided into the high-risk group (n=29) and low-risk group (n=98). The benefit of targeted and immunotherapy in the low-risk group was not distinguishable according to types of agents. However, treatment of Atezolizumab and Bevacizumab appeared to provide longer OS in the high-risk group (12 months vs 9.2, 9, or 5 months for other treatments, p<0.001). Conclusion: The prognostic model constructed by PD-L1, TMB, TERT, and TP53 can identify aHCC patients who would benefit from targeted and immunotherapy, providing insights for the personalized treatment of HCC.

Functional near-infrared spectroscopy-based diagnosis support system for distinguishing between mild and severe depression using machine learning approaches.

Significance: Early diagnosis of depression is crucial for effective treatment. Our study utilizes functional near-infrared spectroscopy (fNIRS) and machine learning to accurately classify mild and severe depression, providing an objective auxiliary diagnostic tool for mental health workers. Aim: Develop prediction models to distinguish between severe and mild depression using fNIRS data. Approach: We collected the fNIRS data from 140 subjects and applied a complete ensemble empirical mode decomposition with an adaptive noise-wavelet threshold combined denoising method (CEEMDAN-WPT) to remove noise during the verbal fluency task. The temporal features (TF) and correlation features (CF) from 18 prefrontal lobe channels of subjects were extracted as predictors. Using recursive feature elimination with cross-validation, we identified optimal TF or CF and examined their role in distinguishing between severe and mild depression. Machine learning algorithms were used for classification. Results: The combination of TF and CF as inputs for the prediction model yielded higher classification accuracy than using either TF or CF alone. Among the prediction models, the SVM-based model demonstrates excellent performance in nested cross-validation, achieving an accuracy rate of 92.8%. Conclusions: The proposed model can effectively distinguish mild depression from severe depression.

A combined pre- and intra-operative nomogram in evaluation of degrees of liver cirrhosis predicts post-hepatectomy liver failure: a multicenter prospective study.

Background: Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data. Methods: Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF. Results: For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram. Conclusions: The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram. Trial Registration: Clinicaltrials.gov Identifier: NCT04076631.

Granulathiazole A protects 6-OHDA-induced Parkinson's disease from ferroptosis via activating Nrf2/HO-1 pathway.

Two pairs of enantiomers (1a-2b), namely (±)-alterpyrone F and (±)-alterpyrone G, along with a rare benzothiazole meroterpenoid granulathiazole A (3, GA), and two undescribed compounds called respectively granulahydeoate (4) and granulaone (5), were obtained from the co-cultivation of Alternaria brassicicola and Penicillium sp. HUBU0120. Exhaustive analyses of NMR, single crystal XRD, Mo2(OAc)4-induced circular dichroism data, and a modified Mosher's method distinguished the absolute configurations of isolates. Bioactive evaluations exhibited that GA possessed promising anti-PD activity in both in vitro and in vivo PD models viz. 6-OHDA-induced SH-SY5Y cells and 6-OHDA-induced zebrafish, respectively. Moreover, our research demonstrated that ferroptosis activated by 6-OHDA was mitigated in PD models after treated with GA. Extensive molecular mechanism studies in PD-modelled cells manifested that GA attenuated the decreased expressions of SLC7A11, GPX4, and FSP-1, and the increased level of ACSL4 via activating Nrf2/HO-1 pathway as well as ameliorated the accumulation of α-synuclein.

FOXP4-AS1 promotes CD8+ T cell exhaustion and esophageal cancer immune escape through USP10-stabilized PD-L1.

Esophageal cancer (EC) is the 9th most frequently diagnosed malignancy globally with unfavorable prognosis. Immune escape is one of the principal factors leading to poor survival, however, the mechanism underlying immune escape remains largely uninvestigated. The xenograft mouse model and EC cell-CD8+ cytotoxic T lymphocytes (CTLs) co-culture system were established. Immunohistochemistry, qRT-PCR or western blot were employed to detect the levels of long non-coding RNA (lncRNA) FOXP4-AS1, PD-L1, USP10 and other molecules. The abundance of T cells, cytokine production and cell apoptosis were monitored by flow cytometry. The viability of CTLs was assessed by Trypan blue staining. The binding between FOXP4-AS1 and USP10 was validated by RNA pull-down assay, and the interaction between USP10 and PD-L1, as well as the ubiquitination of PD-L1, were detected by co-immunoprecipitation. The elevation of FOXP4-AS1 in EC was associated with decreased CTL abundance, and upregulated PD-L1 facilitated CTL apoptosis in EC. FOXP4-AS1 accelerated EC tumor growth by decreasing the abundance of tumor infiltrating CTLs in vivo. FOXP4-AS1 inhibited the viability of CTLs and facilitated the cytotoxicity and exhaustion of CTLs. In Kyse 450 cell-CTL co-culture system, FOXP4-AS1 suppressed the viability and abundance of CTLs, and inhibited EC cell apoptosis via PD-L1. Mechanistically, FOXP4-AS1 regulated the ubiquitination of PD-L1 through deubiquitinating enzyme USP10. FOXP4-AS1 promoted CTL exhaustion and EC immune escape through USP10-stabilized PD-L1. HIGHLIGHTS: PD-L1 facilitated CD8+ T cell apoptosis in EC. Upregulated FOXP4-AS1 promoted EC tumor growth by inhibiting the viability and facilitating the cytotoxicity and exhaustion of tumor infiltrating CD8+ T cells. FOXP4-AS1 suppressed the viability and abundance of CD8+ T cells through USP10-mediated deubiquitination of PD-L1.

Genomic Insights and Synthetic Biology Applications of Marine Actinomycete Streptomyces griseoincarnatus HNS054.

The marine bacterium Streptomyces sp. HNS054 shows promise as a platform for producing natural products. Isolated from a marine sponge, HNS054 possesses several desirable traits for bioengineering: rapid growth, salt tolerance, and compatibility with genetic tools. Its genome contains 21 potential biosynthetic gene clusters, offering a rich source of natural products. We successfully engineered HNS054 to increase the production of aborycin and actinorhodin by 4.5-fold and 1.2-fold, respectively, compared to S. coelicolor M1346 counterparts. With its unique features and amenability to genetic manipulation, HNS054 emerges as a promising candidate for developing novel marine-derived drugs and other valuable compounds.

Anatomical sectionectomy based on Takasaki's segmentation for solitary intrahepatic cholangiocarcinoma: a propensity-matched analysis.

BACKGROUND: Anatomical sectionectomy based on Takasaki's segmentation has shown advantages in hepatocellular carcinoma. However, whether this approach improves the survival of intrahepatic cholangiocarcinoma (ICC) remains unknown. METHODS: A series of 248 consecutive patients with solitary ICCs who underwent hepatectomy were studied retrospectively. The patients were classified into the groups of anatomical sectionectomy based on Takasaki's segmentation (TS group) and non-Takasaki's hepatectomy (NTH group). The bias between the two groups was minimized using propensity score matching (PSM). Recurrence-free survival (RFS) and overall survival (OS) were evaluated with Kaplan-Meier analysis. The Cox proportional hazards model was performed to determine the adverse risk factors associated with survival. RESULTS: After PSM, 67 pairs of patients were compared. Both the RFS and OS rates in the TS group were significantly better than those in the NTH group (23.2 % vs. 16.5 %, and 40.4 % vs. 27.3 %, P = 0.035 and 0.032, respectively). Multivariate analysis showed that NTH was independently associated with worse RFS and OS than TS. The stratified analysis demonstrated that the RFS and OS rates in the TS group with tumor stage I and tumor size ≥3 cm were significantly better than those in the NTH group, while the survival rates for ICC with stage I and tumor size <3 cm or stage II-III showed no significant difference. CONCLUSION: TS was associated with improved RFS and OS in patients with solitary ICC even after PSM. TS may be preferred particularly in patients with tumor stage I and tumor size ≥3 cm.

The challenge of managing ischemic stroke in brucellosis: a case report.

A 64-year-old woman was admitted to the hospital for sudden weakness in one of her left limbs. The patient was diagnosed with acute ischemic stroke (IS) of undetermined cause and received intravenous thrombolysis. Following thrombolysis, the patient's left limb weakness improved, but she subsequently developed recurrent high fever and delirium. Further diagnostic tests revealed that she had been infected with Brucella melitensis. The patient showed significant improvement during anti-infection treatment for Brucellosis and secondary prevention treatment for IS. However, her condition unexpectedly worsened on the 44th day after admission due to a hemorrhagic stroke (HS), which required an urgent craniotomy. Immunohistochemical analysis of the hematoma sample collected during the operation showed the presence of CD4+ and CD8+ T lymphocytes surrounding the blood vessels. This case highlights the unique challenge of managing IS in brucellosis and sheds light on the potential role of T lymphocytes in the immune response related to stroke.

Nomograms confirm serum IL-6 and CRP as predictors of immune checkpoint inhibitor efficacy in unresectable hepatocellular carcinoma.

Background: Immunotherapy based on immune checkpoint inhibitors (ICIs) has become the first-line treatment for unresectable hepatocellular carcinoma (uHCC). However, only a small portion of patients are responsive to ICIs. It is important to identify the patients who are likely to benefit from ICIs in clinical practice. We aimed to examine the significance of serum IL-6 and CRP levels in predicting the effectiveness of ICIs for uHCC. Methods: We retrospectively recruited 222 uHCC patients who received ICIs treatment (training cohort: 124 patients, validation cohort: 98 patients). In the training cohort, patients are categorized into the response group (R) and no-response group (NR). The levels of serum IL-6 and CRP were compared between the two groups. Internal validation was performed in the validation cohort. Survival analysis was carried out using the Kaplan-Meier method and Cox proportional hazard regression model. The nomograms were developed and assessed using the consistency index (C-index) and calibration curve. Results: Serum levels of IL-6 and CRP were significantly lower in the R group than in the NR group (9.94 vs. 36.85 pg/ml, p< 0.001; 9.90 vs. 24.50 mg/L, p< 0.001, respectively). An ROC curve was employed to identify the optimal cut-off values for IL-6 and CRP in both groups, resulting in values of 19.82 pg/ml and 15.50 mg/L, respectively. Multivariate Cox regression analysis revealed that MVI (HR 1.751, 95%CI 1.059-2.894, p=0.029; HR 1.530, 95%CI 0.955-2.451, p=0.077), elevated IL-6 (HR 1.624, 95%CI 1.016-2.596, p=0.043; HR 2.146, 95%CI 1.361-3.383, p =0.001) and high CRP (HR 1.709, 95%CI 1.041-2.807, p=0.034; HR 1.846, 95%CI 1.128-3.022, p = 0.015) were independent risk factors for PFS and OS, even after various confounders adjustments. Nomograms are well-structured and validated prognostic maps constructed from three variables, as MVI, IL6 and CRP. Conclusion: Low levels of IL-6 and CRP have a positive correlation with efficacy for uHCC patients receiving ICIs.

Liver resection versus microwave ablation for solitary and small (≤ 3 cm) HCC with early recurrence in different stages of liver cirrhosis: A propensity score matching study.

BACKGROUND: This study aimed to compare the effectiveness of liver resection (LR) and microwave ablation (MWA) in hepatocellular carcinoma (HCC) patients with early recurrence and varying stages of cirrhosis. METHOD: This study analyzed patients with HCC who underwent hepatectomy and experienced early tumor recurrence (≤3 cm) between December 2002 and December 2020 at the Tongji Hospital. Treatment effectiveness was assessed using a propensity score matching (PSM) analysis. RESULTS: This study included 295 patients (106, LR; 189, MWA), 86 patients in each of the 2 groups were chosen for further comparison, after PSM. After PSM, both LR and MWA demonstrated similar recurrence-free survival (RFS) and overall survival (OS) rates (p = 0.060 and p = 0.118, respectively). However, the LR group had more treatment-related complications. In patients with moderate or severe cirrhosis, no significant differences in RFS or OS rates were found between the LR and MWA groups (p = 0.779 and p = 0.772, respectively). In patients without cirrhosis or with mild cirrhosis, LR showed better RFS and OS rates than MWA (p = 0.024 and p = 0.047, respectively). Multivariate analysis after PSM identified moderate or severe cirrhosis and recurrence intervals ≤12 months as independent predictors of poor RFS and OS in patients with early recurrence of HCC. CONCLUSION: LR is more effective than MWA for early recurrence of HCC in patients without cirrhosis or with mild cirrhosis, showing improved RFS and OS rates. In patients with moderate or severe cirrhosis, the OS and RFS were statistically equal between the two therapies. However, MWA may be preferred owing to its low complication rate.

Phenotypic correlations of carpal gland diverticular number with production traits and its genome-wide association analysis in multiple pig populations.

Pig carpal glands play crucial roles in territorial recognition, reproductive behavior, and information exchange; however, their effects on production traits and underlying genetic mechanisms remain unclear. In this study, 1028 pigs from six populations were counted for the carpal gland diverticular numbers (CGDNs) on the left (CGDNL) and right (CGDNR) legs, and their carcass and meat quality traits were assessed. The CGDNs were significantly different among the populations, and Licha Black pigs had a lower CGDN than the Bama Xiang breed. It was also significantly different between sexes, with males having more diverticula than females (p ≤ 0.0391). Moreover, the number was asymmetric, with CGDNR being significantly higher than CGDNL. Notably, CGDNs was significantly correlated with each other in phenotype and genetics and with 24-h pH, 24-h meat color score, 24-h marbling score, fat content, moisture content, sodium salt content, and saturated fatty acid content in phenotype. Furthermore, genome-wide association analyses identified seven SNPs in association with CGDNs at a 5% genome-wide significance level, all of which were located in a 1.78-Mb (35.347-37.129 Mb) region on chromosome 1. CNC10010837 and CNC10010840 were the top SNPs: both had an additive effect of 0.789 ± 0.120 on CGDNR with p = 8.31E-10. These findings provide important insights into the functions and underlying genetic mechanisms of swine carpal glands.

Interaction of landslide spatial patterns and river canyon landforms: Insights into the Three Parallel Rivers Area, southeastern Tibetan Plateau.

The interaction and mechanism of landslide spatial patterns and river canyon landforms are significant for understanding geomorphic evolution in intensive tectonic alpine environments. This study focuses on the Three Parallel Rivers Area (TPRA) in the southeastern Tibetan Plateau encompassing three parallel rivers (the Nujiang, Lancang, and Jinsha Rivers), to examine the synergistic evolution of geomorphic features and landslides. The analysis revealed a pattern of landslide aggregation in the river valley characterized by the sequence Nujiang > Lancang > Jinsha Rivers. This pattern aligns closely with the distribution of geomorphic indices (local relief, surface erosion index, and threshold slope gradient) in the valleys. As local relief, normalized surface erosion index and normalized threshold slope gradient increase, the mean values of normalized landslide area density (NLAD) rise from around 0.11 to 0.39, 0.16 to 0.48, and 0.10 to 0.21, respectively. Concurrently, the mean values of normalized frequency of landslide dams (NFLD) increase from around 0.05 to 0.24, 0.12 to 0.22, and 0.02 to 0.17, respectively. Additionally, knickpoints could induce upstream suppression and downstream promotion of landslides showcasing the feedback of landslides on the valley landscape. Our findings indicate that the landform formation process in the southeastern Tibetan Plateau orogen is intricately linked to a substantial landsliding response and the observed mass movements vividly mirror the landform formation pattern. These results hold potential implications for understanding the dynamic equilibrium between uplift and surface erosion in the region. This study enhances our understanding of the interaction and mechanisms of landslides and valley landforms.

Portal vein velocity predicts portal vein system thrombosis after splenectomy with esophagogastric devascularization.

BACKGROUND: Portal vein system thrombosis (PVST) is a potentially fatal complication after splenectomy with esophagogastric devascularization (SED) in cirrhotic patients with portal hypertension. However, the impact of portal vein velocity (PVV) on PVST after SED remains unclear. Therefore, this study aims to explore this issue. METHODS: Consecutive cirrhotic patients with portal hypertension who underwent SED at Tongji Hospital between January 2010 and June 2022 were enrolled. The patients were divided into two groups based on the presence or absence of PVST, which was assessed using ultrasound or computed tomography after the operation. PVV was measured by duplex Doppler ultrasound within one week before surgery. The independent risk factors for PVST were analyzed using univariate and multivariate logistic regression analysis. A nomogram based on these variables was developed and internally validated using 1000 bootstrap resamples. RESULTS: A total of 562 cirrhotic patients with portal hypertension who underwent SED were included, and PVST occurred in 185 patients (32.9%). Multivariate logistic regression analysis showed that PVV was the strongest independent risk factor for PVST. The incidence of PVST was significantly higher in patients with PVV ≤ 16.5 cm/s than in those with PVV > 16.5 cm/s (76.2% vs. 8.5%, p < 0.0001). The PVV-based nomogram was internally validated and showed good performance (optimism-corrected c-statistic = 0.907). Decision curve and clinical impact curve analyses indicated that the nomogram provided a high clinical benefit. CONCLUSION: A nomogram based on PVV provided an excellent preoperative prediction of PVST after splenectomy with esophagogastric devascularization.

MGF-net: Multi-channel group fusion enhancing boundary attention for polyp segmentation.

BACKGROUND: Colonic polyps are the most prevalent neoplastic lesions detected during colorectal cancer screening, and timely detection and excision of these precursor lesions is crucial for preventing multiple malignancies and reducing mortality rates. PURPOSE: The pressing need for intelligent polyp detection has led to the development of a high-precision intelligent polyp segmentation network designed to improve polyp screening rates during colonoscopies. METHODS: In this study, we employed ResNet50 as the backbone network and embedded a multi-channel grouping fusion encoding module in the third to fifth stages to extract high-level semantic features of polyps. Receptive field modules were utilized to capture multi-scale features, and grouping fusion modules were employed to capture salient features in different group channels, guiding the decoder to generate an initial global mapping with improved accuracy. To refine the segmentation of the initial global mapping, we introduced an enhanced boundary weight attention module that adaptively thresholds the initial global mapping using learnable parameters. A self-attention mechanism was then utilized to calculate the long-distance dependency relationship of the polyp boundary area, resulting in an output feature map with enhanced boundaries that effectively refines the boundary of the target area. RESULTS: We carried out contrast experiments of MGF-Net with mainstream polyp segmentation networks on five public datasets of ColonDB, CVC-ColonDB, CVC-612, Kvasir, and ETIS. The results demonstrate that the segmentation accuracy of MGF-Net is significantly improved on the datasets. Furthermore, a hypothesis test was conducted to assess the statistical significance of the computed results. CONCLUSIONS: Our proposed MGF-Net outperforms existing mainstream baseline networks and presents a promising solution to the pressing need for intelligent polyp detection. The proposed model is available at https://github.com/xiefanghhh/MGF-NET.

Characteristics of gut bacterial microbiota of black soldier fly (Diptera: Stratiomyidae) larvae effected by typical antibiotics.

As agents in an emerging technology, Hermetia illucens (Linnaeus, 1758) (Diptera: Stratiomyidae) larvae, black soldier fly, have shown exciting potential for degrading antibiotics in organic solid waste, a process for which gut microorganisms play an important role. This study investigated the characteristics of larval gut bacterial communities effected by typical antibiotics. Initially, antibiotics significantly reduced the diversity of gut bacterial species. After 8 days, diversity recovered to similar to that of the control group in the chlortetracycline, tylosin, and sulfamethoxazole groups. Proteobacteria, Firmicutes, and Actinobacteriota were the dominant phyla at the initial BSFL gut. However, after 4 days treatment, the proportion of Actinobacteriota significantly decreased, but Bacteroidota notably increased. During the conversion process, 18, 18, 17, 21, and 19 core genera were present in the chlortetracycline, sulfamethoxazole, tylosin, norfloxacin, and gentamicin groups, respectively. Pseudomonas, Actinomyces, Morganella, Providencia and Klebsiella might be the important genera with extraordinary resistance and degradation to antibiotics. Statistical analyses of COGs showed that antibiotics changed the microbial community functions of BSFL gut. Compared with the control group, (i) the chlortetracycline, sulfamethoxazole, and tylosin groups showed significant increase in the classification functions of transcription, RNA processing and modification，and so on, (ii) the norfloxacin and gentamicin groups showed significant increase in defense mechanisms and other functions. Note that we categorized the response mechanisms of these classification functions to antibiotics into resistance and degradation. This provides a new perspective to deeply understand the joint biodegradation behavior of antibiotics in environments, and serves as an important reference for further development and utilization of microorganisms-assisted larvae for efficient degradation of antibiotics.

Brassisterol A, a new ergosterol from co-cultivation of fungi attenuates neuroinflammation via targeting NLRP3/caspase-1/GSDMD pathway.

Three new ergosterol derivatives brassisterol A-C (1-3) and two new epimeric bicycle-lactones brassictones A and B (4 and 5), were isolated from the co-cultivation of Alternaria brassicicola and Penicillium granulatum. The absolute configurations of these isolates were confirmed by extensive NMR spectra, TD-DFT ECD calculation, and the single crystal XRD data analysis. Amongst the metabolites, compound 1 exhibited potential anti-Parkinson's disease activity in both MPTP-induced zebrafish and MPP+-induced SH-SY5Y cells. Molecular mechanism studies in vitro showed that 1 attenuated the increase of α-synuclein, NLRP3, ASC, caspase-1, IL-1ß, IL-18, and GSDMD expression in the MPP+ induced PD model. Molecular docking in silico simulations exhibited that 1 was well accommodated to one of the binding pockets of NLRP3 8ETR in an appropriate conformation via forming typical hydrogen bonds as well as possessing a high negative binding affinity (-8.97 kcal/mol). Thus, our work suggested that 1 protected dopaminergic cell from neuroinflammation via targeting NLRP3/caspase-1/GSDMD signaling pathway.

Genome sequencing and metabolic network reconstruction of a novel sulfur-oxidizing bacterium Acidithiobacillus Ameehan.

Sulfur-oxidizing bacteria play a crucial role in various processes, including mine bioleaching, biodesulfurization, and treatment of sulfur-containing wastewater. Nevertheless, the pathway involved in sulfur oxidation is highly intricate, making it complete comprehension a formidable and protracted undertaking. The mechanisms of sulfur oxidation within the Acidithiobacillus genus, along with the process of energy production, remain areas that necessitate further research and elucidation. In this study, a novel strain of sulfur-oxidizing bacterium, Acidithiobacillus Ameehan, was isolated. Several physiological characteristics of the strain Ameehan were verified and its complete genome sequence was presented in the study. Besides, the first genome-scale metabolic network model (AMEE_WP1377) was reconstructed for Acidithiobacillus Ameehan to gain a comprehensive understanding of the metabolic capacity of the strain.The characteristics of Acidithiobacillus Ameehan included morphological size and an optimal growth temperature range of 37-45°C, as well as an optimal growth pH range of pH 2.0-8.0. The microbe was found to be capable of growth when sulfur and K2O6S4 were supplied as the energy source and electron donor for CO2 fixation. Conversely, it could not utilize Na2S2O3, FeS2, and FeSO4·7H2O as the energy source or electron donor for CO2 fixation, nor could it grow using glucose or yeast extract as a carbon source. Genome annotation revealed that the strain Ameehan possessed a series of sulfur oxidizing genes that enabled it to oxidize elemental sulfur or various reduced inorganic sulfur compounds (RISCs). In addition, the bacterium also possessed carbon fixing genes involved in the incomplete Calvin-Benson-Bassham (CBB) cycle. However, the bacterium lacked the ability to oxidize iron and fix nitrogen. By implementing a constraint-based flux analysis to predict cellular growth in the presence of 71 carbon sources, 88.7% agreement with experimental Biolog data was observed. Five sulfur oxidation pathways were discovered through model simulations. The optimal sulfur oxidation pathway had the highest ATP production rate of 14.81 mmol/gDW/h, NADH/NADPH production rate of 5.76 mmol/gDW/h, consumed 1.575 mmol/gDW/h of CO2, and 1.5 mmol/gDW/h of sulfur. Our findings provide a comprehensive outlook on the most effective cellular metabolic pathways implicated in sulfur oxidation within Acidithiobacillus Ameehan. It suggests that the OMP (outer-membrane proteins) and SQR enzymes (sulfide: quinone oxidoreductase) have a significant impact on the energy production efficiency of sulfur oxidation, which could have potential biotechnological applications.

Intelectin-1 is a novel prognostic biomarker for hepatocellular carcinoma.

The molecular mechanisms of hepatocellular carcinoma (HCC) are still not well understood. Gene microarray analysis showed that the expression of Intelectin-1 (ITLN-1) in tumor-adjacent normal liver tissue was 454.8 times higher than in the corresponding cancer tissue. ITLN-1 is a secreted soluble glycoprotein which has been reported to be associated with the occurrence and development of various tumor types. However, the prognostic significance of ITLN-1 in HCC remain unclear. Real-time fluorescence quantitative polymerase chain reaction was used to investigate 149 liver cancer cases for ITLN-1 mRNA expression. Immunohistochemistry and western blot analysis were used to ascertain protein expression of ITLN-1 in cancer and para-carcinomatous tissue, and further to evaluate the correlation between ITLN-1 mRNA expression and surgical prognosis after liver resection. The ITLN-1 mRNA and protein levels were significantly higher in adjacent normal liver tissues than HCC tissues. Real-time fluorescence quantitative polymerase chain reaction showed that the ITLN-1 expression was decreased in 78.5% (117/149) of HCC tissues compared with their corresponding adjacent liver tissues. Moreover, its low expression was significantly correlated with increased tumor size, tumor differentiation degree, degree of liver cirrhosis, capsule integrity, vascular invasion and tumor recurrence. Patients with high ITLN-1 expression had significantly better overall and recurrence-free survival after curative liver resection. Multivariate cox regression analysis showed that ITLN-1 was an independent predictor of surgical outcomes in HCC patients. The present study suggested that low ITLN-1 expression was associated with poor clinical outcome for HCC patients, indicating a novel biomarker for prognosis evaluation and a potential therapeutic target for HCC patients.