Initial investigation on ultrasound-guided percutaneous biopsy of lesions in the first hepatic hilum with fusion of ultrasound and multimodal imaging cognitive guidance.

Purpose: This study aims to evaluate the efficacy and safety of ultrasound-guided percutaneous biopsy of the first hepatic hilum lesion, and examine its clinical value of diagnosis and treatment. Methods: We conducted a retrospective study on patients diagnosed with the first hepatic hilum lesions at Fujian Provincial Hospital between February 2015 and October 2022. We selected patients who had lesions in the first hepatic hilum(including a 2cm surrounding area of the left/right hepatic ducts and upper-middle segment of the common bile duct) and the liver periphery(in the peripheral area of the liver, outside of the above-mentioned first hepatic porta region). These patients underwent percutaneous ultrasound-guided core needle biopsy (PUS-CNB) with cognitive fusion guidance using CT, MRI, or PET-CT. We compared the safety and efficacy of PUS-CNB in the first hepatic hilum and the liver periphery to explore the value of PUS-CNB in optimizing the clinical treatment of the first hepatic hilum lesions. Results: The studied includes 38 cases of the first hepatic hilum cases (18 females; 20 males), 23 presented with mass-forming tumors while the remaining 15 exhibited diffuse infiltrative tumors, with an average diameter of 4.65± 2.51 cm. The percutaneous biopsy procedure, conducted under ultrasound guidance, had an average operation time of 14.55 ± 2.73 minutes, and resulted in a postoperative bleeding volume of approximately 10.79 ± 2.79 ml. The diagnostic success rate was noted to be as high as 92.11% among the participants who underwent percutaneous biopsy of the first hepatic hilum. Procedural complications, such as bleeding, bile leakage, intestinal perforation, infection or needle tract seeding, did not occur during or after the biopsy procedure. Affected by biopsy results, 5 altered their clinical treatment plans accordingly, 24patients received non-surgical treatment, 9 underwent surgical treatment, 5 underwent radiofrequency ablation for the lesions. The study comprised a total of 112 cases for percutaneous biopsy of the liver periphery. The safety and effectiveness of the two biopsy techniques were comparable, with diagnostic success rates of 92.11% VS. 94.34%, respectively (p = 0.61). Conclusion: Cognitive fusion of ultrasound and multi-modal imaging for the first hepatic hilum lesion puncture biopsy is a safe and effective diagnostic procedure, with better diagnostic rate, may improve clinical value of diagnosis and treatment of various diseases.

GCN2 in Viral Defence and the Subversive Tactics Employed by Viruses.

The recent SARS-CoV-2 pandemic and associated COVID19 disease illustrates the important role of viral defence mechanisms in ensuring survival and recovery of the host or patient. Viruses absolutely depend on the host's protein synthesis machinery to replicate, meaning that impeding translation is a powerful way to counteract viruses. One major approach used by cells to obstruct protein synthesis is to phosphorylate the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α). Mammals possess four different eIF2α-kinases: PKR, HRI, PEK/PERK, and GCN2. While PKR is currently considered the principal eIF2α-kinase involved in viral defence, the other eIF2α-kinases have also been found to play significant roles. Unsurprisingly, viruses have developed mechanisms to counteract the actions of eIF2α-kinases, or even to exploit them to their benefit. While some of these virulence factors are specific to one eIF2α-kinase, such as GCN2, others target all eIF2α-kinases. This review critically evaluates the current knowledge of viral mechanisms targeting the eIF2α-kinase GCN2. A detailed and in-depth understanding of the molecular mechanisms by which viruses evade host defence mechanisms will help to inform the development of powerful anti-viral measures.

Analysis of urinary retention after endoscopic prostate enucleation and its subsequent impact on surgical outcomes.

PURPOSE: Postoperative urinary retention (PUR) is a common complication after prostate enucleation, which leads to an increased length of hospital stay and decreased postoperative satisfaction. This study determined the predictive factors of postoperative urine retention within 1 month after prostate enucleation and investigated whether PUR influences surgical outcomes at the 2-week, 3-month, and 6-month follow-up time points. METHODS: Data were collected from the electronic medical records of 191 patients with benign prostatic obstruction (BPO) during October 2018 to September 2021. Of them, 180 patients who underwent thulium laser or plasma kinetic enucleation of the prostate (ThuLEP, PKEP) were separated into the PUR group (n = 24) and the non-PUR (NPUR) group (n = 156). Uroflowmetry and the International Prostate Symptom Score (IPSS) questionnaire were followed up at 2 weeks, 3 months, and 6 months postoperatively. RESULTS: The PUR group had a significantly higher percentage of patients with type 2 diabetes mellitus (DM) than the NPUR group. Postoperatively, compared with the NPUR group, the PUR group had significantly less improvement in changes in the IPSS Quality of Life scores at 2 weeks, the total IPSS(International Prostate Symptom Score) at all follow-up times, the IPSS-S(IPSS storage subscores) at 2 weeks and 3 months, and the IPSS-V(IPSS voiding subscores) at all follow-up times. Predictive factors for PUR include lower preoperative maximum urinary flow (Qmax), lower preoperative total IPSS, and higher operation time. CONCLUSION: Lower preoperative Qmax, lower IPSS scores, and longer operation time were risk factors for PUR. Furthermore, PUR could be a prognostic factor for prostatic enucleation surgical outcomes.

Development and optimization of a DNA aptamer to delay ß-bungarotoxin-induced lethality in a rodent model.

Current treatment of snakebite relies on immunoglobulin-rich antivenoms. However, production of these antivenoms is complicated and costly. Aptamers - single-stranded DNAs or RNAs with specific folding structures that bind to specific target molecules - represent excellent alternatives or complements to antibody-based therapeutics. However, no studies have systematically assessed the feasibility of using aptamers to mitigate venom-induced toxicity in vivo. ß-bungarotoxin is the predominant protein responsible for the toxicity of the venom of Bungarus multicinctus, a prominent venomous snake inhabiting Taiwan. In this study, we reported the screening and optimization of a DNA aptamer against ß-bungarotoxin and tested its utility in a mouse model. After 14 rounds of directed evolution of ligands by exponential enrichment, an aptamer, called BB3, displaying remarkable binding affinity and specificity for ß-bungarotoxin was obtained. Following structural prediction and point-modification experiments, BB3 underwent truncation and was modified with 2'-O-methylation and a 3'-inverted dT. This optimized aptamer showed sustained, high-affinity binding for ß-bungarotoxin and exhibited remarkable nuclease resistance in plasma. Importantly, administration of this optimized aptamer extended the survival time of mice treated with a lethal dose of ß-bungarotoxin. Collectively, our data provide a compelling illustration of the potential of aptamers as promising candidates for development of recombinant antivenom therapies.

Endocrine disruptor-induced epimutagenesis in vitro : Insight into molecular mechanisms.

Endocrine disrupting chemicals (EDCs) such as bisphenol S (BPS) are xenobiotic compounds that can disrupt endocrine signaling following exposure due to steric similarities to endogenous hormones within the body. EDCs have been shown to induce disruptions in normal epigenetic programming (epimutations) that accompany dysregulation of normal gene expression patterns that appear to predispose disease states. Most interestingly, the prevalence of epimutations following exposure to many different EDCs often persists over multiple subsequent generations, even with no further exposure to the causative EDC. Many previous studies have described both the direct and prolonged effects of EDC exposure in animal models, but many questions remain about molecular mechanisms by which EDCs initially induce epimutations or contribute to the propagation of EDC-induced epimutations either within the exposed generation or to subsequent generations. Additional questions remain regarding the extent to which there may be differences in cell-type specific susceptibilities to various EDCs, and whether this susceptibility is correlative with expression of relevant hormone receptors and/or the location of relevant hormone response elements (HREs) in the genome. To address these questions, we exposed cultured mouse pluripotent (induced pluripotent stem [iPS]), somatic (Sertoli and granulosa), and germ (primordial germ cell like [PGCLC]) cells to BPS and measured changes in DNA methylation levels at the epigenomic level and gene expression at the transcriptomic level. We found that there was indeed a difference in cell-type specific susceptibility to EDC-induced epimutagenesis and that this susceptibility correlated with differential expression of relevant hormone receptors and, in many cases, tended to generate epimutations near relevant HREs within the genome. Additionally, however, we also found that BPS can induce epimutations in a cell type that does not express relevant receptors and in genomic regions that do not contain relevant HREs, suggesting that both canonical and non-canonical signaling mechanisms can be disrupted by BPS exposure. Most interestingly, we found that when iPS cells were exposed to BPS and then induced to differentiate into PGCLCs, the prevalence of epimutations and differentially expressed genes (DEGs) initially induced in the iPSCs was largely retained in the resulting PGCLCs, however, >90% of the specific epimutations and DEGs were not conserved but were rather replaced by novel epimutations and DEGs following the iPSC to PGCLC transition. These results are consistent with a unique concept that many EDC-induced epimutations may normally be corrected by germline and/or embryonic epigenetic reprogramming but that due to disruption of the underlying chromatin architecture induced by the EDC exposure, many novel epimutations may emerge during the reprogramming process as well. Thus, it appears that following exposure to a disruptive agent such as an EDC, a prevalence of epimutations may transcend epigenetic reprogramming even though most individual epimutations are not conserved during this process.

The efficacy and safety of adding PD-1 blockade to induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) for locoregionally advanced nasopharyngeal carcinoma: an observational, propensity score-matched analysis.

BACKGROUND: Despite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC  plus cisplatin CCRT ) for LANPC patients. METHODS: From January 2020 to November 2022, 347 patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0) were included. Of the 347 patients, 268 patients were treated with standard treatment (IC-CCRT), and 79 received PD-1 blockade plus IC-CCRT (PD-1 group). For the PD-1 group, PD-1 blockade was given intravenously once every 3 weeks for up to 9 cycles (3 induction and 6 adjuvant). The primary endpoint was disease-free survival (DFS) (i.e. freedom from local/regional/distant failure or death). The propensity score matching (PSM) with the ratio of 1:2 was performed to control confounding factors. RESULTS: After PSM analysis, 150 patients receiving standard treatment and 75 patients receiving additional PD-1 blockade remained in the current analysis. After three cycles of IC, the PD-1 group had significantly higher rates of complete response (defined as disappearance of all target lesions; 24% vs. 9%; P = 0.006) and complete biological response (defined as undetectable cell-free Epstein-Barr virus DNA, cfEBV DNA; 79% vs. 65%; P = 0.046) than that in the standard group. And the incidence of grade 3-4 toxicity during IC was 47% in the PD-1 group and 41% in the standard group, with no significant difference (P = 0.396). During follow-up period, additional PD-1 blockade to standard treatment improved 3-year DFS from 84 to 95%, with marginal statistical significance (HR, 0.28; 95%CI, 0.06-1.19; P = 0.064). CONCLUSION: Additiaonl PD-1 blockade to gemcitabine and cisplatin IC and adjuvant treatment results in significant improvement in tumor regression, cfEBV DNA clearance, superior DFS, and comparable toxicity profiles in high-risk LANPC patients.

A Chinese patent medicine's long-term efficacy on non-dialysis patients with CKD stages 3-5: a retrospective cohort study.

Background: Chinese patent medicine is commonly used in China as an important treatment mechanism to thwart the progression of chronic kidney disease (CKD) stages 3-5, among which Niaoduqing granules are a representative Chinese patent medicine; however, its long-term efficacy on CKD prognosis remains unclear. Methods: Patients were grouped according to Niaoduqing granule prescription duration (non-Niaoduqing granule (non-NDQ) group vs Niaoduqing granule (NDQ) group). Serum creatinine (SCr) variation was compared using a generalized linear mixed model (GLMM). Multivariate Cox regression models were constructed, adjusting for confounding factors, to explore the risk of composite outcomes (receiving renal replacement therapy (RRT) or having an estimated glomerular filtration rate (eGFR)<5 mL/min/1.73 m2, ≥50% decline in the eGFR from the baseline, and doubling of SCr) in individuals consuming Niaoduqing granules. Results: A total of 1,271 patients were included, with a median follow-up duration of 29.71 (12.10, 56.07) months. The mean SCr Z-scores for the non-NDQ group and NDQ group were -0.175 and 0.153, respectively, at baseline (p = 0.015). The coefficients of the NDQ group from visit 1 to visit 5 were -0.207 (95% CI: -0.346, -0.068, p = 0.004), -0.214 (95% CI: 0.389, -0.039, p = 0.017), -0.324 (95% CI: 0.538, -0.109, p = 0.003), -0.502 (95% CI: 0.761, -0.243, p = 0.000), and -0.252 (95% CI: 0.569, 0.065, p = 0.119), respectively. The survival probability was significantly higher in the NDQ group (p = 0.0039). Taking Niaoduqing granules was a significant protective factor for thwarting disease progression (model 1: HR 0.654 (95% CI 0.489-0.875, p = 0.004); model 2: HR 0.646 (95% CI 0.476, 0.877, p = 0.005); and model 3: HR 0.602 (95% CI 0.442, 0.820, p = 0.001)). Conclusion: The long-term use of Niaoduqing granules improved SCr variation and lowered the risk of CKD progression by 39.8%.

Electroneutralization desalination with spontaneous chemoelectric power generation.

This study designs a novel electroneutralization desalination cell using reaction heat from acidic-alkaline wastewater neutralization to desalinate wastewater and generates chemoelectric power. Several key performance indicators are measured in terms of the energy, environmental and economic aspects of the system, including the ionic flux, the electrical energy produced, the electrical energy consumption for desalination, parasitic losses, overall energy conversion efficiency and desalination performance. The maximum peak power density is ∼31.5 mW/cm2 at 83.5 mA/cm2 and the desalination efficiency is 62 % using brine. The overall energy conversion efficiency is ∼81.8 % and the desalination followed the zero-order reaction. Assuming a 1.5 million litres per day treatment capacity integrated with reverse osmosis, the system has environmental and economic benefits, with 44.5 kg-CO2eq greenhouse gas emissions per cubic meter of treated brine, and a discounted payback period of 4.2 years. This study demonstrates a pioneering electroneutralization technique for self-sufficient brine valorization and wastewater reclamation.

Comparison of genomic prediction methods for early growth traits of Inner Mongolia cashmere goats based on multi trait models.

Inner Mongolia cashmere goat is an excellent livestock breed formed through long-term natural selection and artificial breeding, and is currently a world-class dual-purpose breed producing cashmere and meat. Multi trait animal model is considered to significantly improve the accuracy of genetic evaluation in livestock and poultry, enabling indirect selection between traits. In this study, the pedigree, genotype, environment, and phenotypic records of early growth traits of Inner Mongolia cashmere goats were used to build multi trait animal model., Then three methods including ABLUP, GBLUP, and ssGBLUP wereused to estimate the genetic parameters and genomic breeding values of early growth traits (birth weight, weaning weight, average daily weight gain before weaning, and yearling weight). The accuracy and reliability of genomic estimated breeding value are further evaluated using the five fold cross validation method. The results showed that the heritability of birth weight estimated by three methods was 0.13-0.15, the heritability of weaning weight was 0.13-0.20, heritability of daily weight gain before weaning was 0.11-0.14, and the heritability of yearling weight was 0.09-0.14, all of which belonged to moderate to low heritability. There is a strong positive genetic correlation between weaning weight and daily weight gain before weaning, daily weight gain before weaning and yearling weight, with correlation coefficients of 0.77-0.79 and 0.56-0.67, respectively. The same pattern was found in phenotype correlation among traits. The accuracy of the estimated breeding values by ABLUP, GBLUP, and ssGBLUP methods for birth weight is 0.5047, 0.6694, and 0.7156, respectively; the weaning weight is 0.6207, 0.6456, and 0.7254, respectively; the daily weight gain before weaning was 0.6110, 0.6855, and 0.7357 respectively; and the yearling weight was 0.6209, 0.7155, and 0.7756, respectively. In summary, the early growth traits of Inner Mongolia cashmere goats belong to moderate to low heritability, and the speed of genetic improvement is relatively slow. The genetic improvement of other growth traits can be achieved through the selection of weaning weight. The ssGBLUP method has the highest accuracy and reliability in estimating genomic breeding value of early growth traits in Inner Mongolia cashmere goats, and is significantly higher than that from ABLUP method, indicating that it is the best method for genomic breeding of early growth weight in Inner Mongolia cashmere goats.

Concurrent Joint Contact in Anterior Cruciate Ligament Injury induces cartilage micro-injury and subchondral bone sclerosis, resulting in knee osteoarthritis.

Objective: Anterior Cruciate Ligament (ACL) injury develops the Osteoarthritis (OA) via two distinct processes: initial direct micro-injury of the cartilage surface by compressive force during ACL injury, and secondary joint instability due to the deficiency of the ACL. Using the conventional Compression-induced ACL-R and novel Non-Compression ACL-R models, we aimed to reveal the individual effects on OA progression after ACL injury. Methods: Twelve-week-old C57BL/6 male were randomly divided to three experimental groups: Compression ACL-R, Non-Compression ACL-R, and Intact. We performed the joint laxity test and microscope analysis at 0 days, in vivo imaging with matrix-metalloproteinases (MMPs) at 3 and 7 days, histological and micro-CT analysis at 0, 7, 14, and 28 days. Results: Although no differences in the joint laxity were observed between both ACL-R groups, the Compression ACL-R group exhibited a significant increase of cartilage roughness immediately after injury compared with the Non-Compression group. At 7 days, Compression group increased MMPs-induced fluorescence intensity slightly and MMP-13 positive cell ratio of chondrocytes significantly than that in the Non-Compression group. Moreover, histological cartilage degeneration initiated in the whole joint level of the Compression group at the same time point. Micro-CT analysis revealed that sclerosis of tibial Subchondral bone in the Compression group developed significantly more than in the Non-Compression group at 28 days, especially in the medial tibial compartment. Conclusions: Concurrent joint contact during ACL rupture caused initial micro-damage on the cartilage surface and early cartilage degeneration with MMP-13 production, leading to later bone formation in the subchondral bone.

METTL14 regulates CD8+T-cell activation and immune responses to anti-PD-1 therapy in lung cancer.

BACKGROUND: N6-methyladenosine (m6A) modification plays an important role in lung cancer. However, methyltransferase-like 14 (METTL14), which serves as the main component of the m6A complex, has been less reported to be involved in the immune microenvironment of lung cancer. This study aimed to analyze the relationship between METTL14 and the immune checkpoint inhibitor programmed death receptor 1 (PD-1) in lung cancer. METHODS: CCK-8, colony formation, transwell, wound healing, and flow cytometry assays were performed to explore the role of METTL14 in lung cancer progression in vitro. Furthermore, syngeneic model mice were treated with sh-METTL14 andan anti-PD-1 antibody to observe the effect of METTL14 on immunotherapy. Flow cytometry and immunohistochemical (IHC) staining were used to detect CD8 expression. RIP and MeRIP were performed to assess the relationship between METTL14 and HSD17B6. LLC cells and activated mouse PBMCs were cocultured in vitro to mimic immune cell infiltration in the tumor microenvironment. ELISA was used to detect IFN-γ and TNF-α levels. RESULTS: The online database GEPIA showed that high METTL14 expression indicated a poor prognosis in patients with lung cancer. In vitro assays suggested that METTL14 knockdown suppressed lung cancer progression. In vivo assays revealed that METTL14 knockdown inhibited tumor growth and enhanced the response to PD-1 immunotherapy. Furthermore, METTL14 knockdown enhanced CD8+T-cell activation and infiltration. More importantly, METTL14 knockdown increased the stability of HSD17B6 mRNA by reducing its m6A methylation. In addition, HSD17B6 overexpression promoted the activation of CD8+ T cells. CONCLUSION: The disruption of METTL14 contributed to CD8+T-cell activation and the immunotherapy response to PD-1 via m6A modification of HSD17B6, thereby suppressing lung cancer progression.

Comparison of cytokine expression and disease severity between plasma cell-dominant and eosinophil-dominant patients in chronic rhinosinusitis with nasal polyps.

PURPOSE: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease characterized by inflammation of the nasal and sinus mucosa. The inflammatory patterns may differ among patients, leading to different subtypes based on the dominant inflammatory cell type. This study aimed to compare the differences in cytokine expression and disease severity between plasma cell-dominant and eosinophil-dominant subtypes in patients with CRSwNP. METHODS: This study included 53 CRSwNP patients and 19 control subjects who did not have asthma or a history of cigarette smoking. The expression of cytokines and inflammatory cells was assessed via enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. RESULTS: Among the cytokines analyzed, only IL-6 was significantly different between the two subtypes. A greater proportion of mast cells and IgE cells was present in plasma cell-dominant CRSwNP patients than in eosinophil-dominant group. For the three disease severity scores (LMK-CT, TPS and SNOT-22), objective scores (LMK-CT and TPS) were greater in the eosinophil-dominant CRSwNP group, while the opposite result was shown for the subjective score (SNOT-22). Additionally, the percentage of plasma cell-dominant cells was significantly positively correlated with disease severity according to the TPS and SNOT-22 scores. CONCLUSIONS: Our data revealed that plasma cell-dominant inflammation, a subtype of type 2 CRS, was significantly correlated with subjective disease severity. The study also highlights the role of IL-6, IgE and mast cells as distinguishing factors between eosinophil-dominant and plasma cell-dominant CRSwNP. This information could be useful for clinical diagnosis and personalized treatment.

BRCA1 safeguards genome integrity by activating chromosome asynapsis checkpoint to eliminate recombination-defective oocytes.

In the meiotic prophase, programmed DNA double-strand breaks are repaired by meiotic recombination. Recombination-defective meiocytes are eliminated to preserve genome integrity in gametes. BRCA1 is a critical protein in somatic homologous recombination, but studies have suggested that BRCA1 is dispensable for meiotic recombination. Here we show that BRCA1 is essential for meiotic recombination. Interestingly, BRCA1 also has a function in eliminating recombination-defective oocytes. Brca1 knockout (KO) rescues the survival of Dmc1 KO oocytes far more efficiently than removing CHK2, a vital component of the DNA damage checkpoint in oocytes. Mechanistically, BRCA1 activates chromosome asynapsis checkpoint by promoting ATR activity at unsynapsed chromosome axes in Dmc1 KO oocytes. Moreover, Brca1 KO also rescues the survival of asynaptic Spo11 KO oocytes. Collectively, our study not only unveils an unappreciated role of chromosome asynapsis in eliminating recombination-defective oocytes but also reveals the dual functions of BRCA1 in safeguarding oocyte genome integrity.

Determining cut-off values and predictors for the Snaith-Hamilton Pleasure Scale: comparison between clinical and school settings.

BACKGROUND: Few previous studies have established Snaith-Hamilton Pleasure Scale (SHAPS) cut-off values using receiver operating characteristic curve analysis and applied these values to compare predictors of anhedonia between clinical and nonclinical groups. AIMS: To determine the optimal cut-off values for the SHAPS and use them to identify predictors of anhedonia in clinical and nonclinical groups in Taiwan. METHOD: This cross-sectional and correlational study used convenience sampling to recruit 160 patients from three hospitals and 412 students from two universities in northern Taiwan. Data analysis included receiver operating characteristic curve, univariate and multivariate analyses. RESULTS: The optimal SHAPS cut-off values were 29.5 and 23.5 for the clinical and nonclinical groups, respectively. Moreover, two-stage analysis revealed that participants in the clinical group who perceived themselves as nondepressed, and participants in the nonclinical group who did not skip classes and whose fathers exhibited higher levels of care and protection were less likely to attain the cut-off values. Conversely, participants in the nonclinical group who reported lower academic satisfaction and were unwilling to seek help from family or friends were more likely to attain the cut-off values. CONCLUSIONS: Our findings highlight the importance of optimal cut-off values in screening for depression risk within clinical and nonclinical groups. Accordingly, the development of comprehensive, individualised programmes to monitor variation trends in SHAPS scores and relevant predictors of anhedonia across different target populations is crucial.

Stochastic processes shape microbial community assembly in biofilters: Hidden role of rare taxa.

Stochastic and deterministic processes are the major themes governing microbial community assembly; however, their roles in bioreactors are poorly understood. Herein, the mechanisms underlying microbial assembly and the effect of rare taxa were studied in biofilters. Phylogenetic tree analysis revealed differences in microbial communities at various stages. Null model analysis showed that stochastic processes shaped the community assembly, and deterministic processes emerged only in the inoculated activated sludge after domestication. This finding indicates the dominant role of stochastic factors (biofilm formation, accumulation, and aging). The Sloan neutral model corroborated the advantages of stochastic processes and mainly attributed these advantages to rare taxa. Cooccurrence networks revealed the importance of rare taxa, which accounted for more than 85% of the keystones. Overall, these results provide good foundations for understanding community assembly, especially the role of rare taxa, and offer theoretical support for future community design and reactor regulation.

Color-coded collateral and venous outflow patterns in estimating infarct progression and predicting functional independence for stroke patients in late time window.

OBJECTIVES: To investigate whether cerebral collateral and venous outflow patterns on color-coded multi-phase computed tomography angiography (mCTA) can estimate ischemic core growth rate (IGR) and predict 90-day functional independence for patients with late-presenting acute ischemic stroke (AIS). METHODS: The retrospective analysis included 127 AIS patients with a late time window. All patients underwent baseline mCTA with color-coded reconstruction and computed tomography perfusion. Both collateral score and venous outflow (VO) score on color-coded mCTA maps were analyzed and recorded. The IGR was calculated as ischemic core volume divided by the time from onset to imaging. A 90-day modified Rankin Scale score of 0-2 was defined as functional independence. Kendall's Tau-b analysis was used for nonparametric correlation analysis. Propensity scores, logistic regressions, and receiver operator characteristic (ROC) curves were applied to construct the prediction model. RESULTS: Moderate correlations were found between collateral delay and IGR (Tau-b = -0.554) and between VO and IGR (Tau-b = -0.501). High collateral score (odds ratio = 3.01) and adequate VO (odds ratio = 4.89) remained independent predictors for 90-day functional independence after adjustment. The joint predictive model, which integrated the VO score and clinical features, demonstrated an area under the ROC curve (AUC) of 0.878. The AUCs of collateral score and VO score were 0.836 and 0.883 for outcome prediction after adjustment. CONCLUSIONS: Cerebral collateral and VO patterns based on color-coded mCTA can effectively predict infarct progression and 90-day clinical outcomes, even for AIS patients beyond the routine time window. ADVANCES IN KNOWLEDGE: Color-coded mCTA is a readily understandable post-processing technique for the rapid assessment of collateral circulation and VO status in stroke imaging. A moderate correlation was observed between the characteristics of collateral delay/VO on color-coded mCTA and IGR in patients with acute ischemic stroke. Both high-quality collateral circulation and "red superficial middle cerebral vein sign" can predict 90-day functional independence even for patients beyond the routine time window.

Surgical restabilization reduces the progression of post-traumatic osteoarthritis initiated by ACL rupture in mice.

OBJECTIVE: People who sustain joint injuries such as anterior cruciate ligament (ACL) rupture often develop post-traumatic osteoarthritis (PTOA). In human patients, ACL injuries are often treated with ACL reconstruction. However, it is still unclear how effective joint restabilization is for reducing the progression of PTOA. The goal of this study was to determine how surgical restabilization of a mouse knee joint following non-invasive ACL injury affects PTOA progression. DESIGN: In this study, 187 mice were subjected to non-invasive ACL injury or no injury. After injury, mice underwent restabilization surgery, sham surgery, or no surgery. Mice were then euthanized on day 14 or day 49 after injury/surgery. Functional analyses were performed at multiple time points to assess voluntary movement, gait, and pain. Knees were analyzed ex vivo with micro-computed tomography, RT-PCR, and whole-joint histology to assess articular cartilage degeneration, synovitis, and osteophyte formation. RESULTS: Both ACL injury and surgery resulted in loss of epiphyseal trabecular bone (-27-32%) and reduced voluntary movement at early time points. Joint restabilization successfully lowered OA score (-78% relative to injured at day 14, p < 0.0001), and synovitis scores (-37% relative to injured at day 14, p = 0.042), and diminished the formation of chondrophytes/osteophytes (-97% relative to injured at day 14, p < 0.001, -78% at day 49, p < 0.001). CONCLUSIONS: This study confirmed that surgical knee restabilization was effective at reducing articular cartilage degeneration and diminishing chondrophyte/osteophyte formation after ACL injury in mice, suggesting that these processes are largely driven by joint instability in this mouse model. However, restabilization was not able to mitigate the early inflammatory response and the loss of epiphyseal trabecular bone, indicating that these processes are independent of joint instability.

Semaglutide combined with empagliflozin vs. monotherapy for non-alcoholic fatty liver disease in type 2 diabetes: Study protocol for a randomized clinical trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM). Lifestyle intervention remains a preferred treatment modality for NAFLD. The glucagon-like peptide (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been developed as new glucose-lowering drugs, which can improve fatty liver via an insulin-independent glucose-lowering effect. However, studies exploring the efficacy of GLP-1 receptor agonists combined with SGLT-2 inhibitors in patients with NAFLD and T2DM are scanty. Thus, the present randomised controlled trial aims at comparing the efficacy and safety of semaglutide plus empagliflozin with each treatment alone in patients with NAFLD and T2DM. METHODS: This 52-week double-blinded, randomised, parallel-group, active-controlled trial evaluates the effects of semaglutide, empagliflozin and semaglutide + empagliflozin in 105 eligible overweight/obese subjects with NAFLD and T2DM. The primary outcome will be a change from baseline to week 52 in the controlled attenuation parameter, free fatty acid and glucagon. Secondary endpoints include changes in liver stiffness measurement, liver enzymes, blood glucose, lipid levels, renal function, electrolyte balances, minerals and bone metabolism, cytokines, high-sensitivity C-reactive protein, ferritin, anthropometric indicators, nonalcoholic fatty liver fibrosis score, fibrosis 4 score and homeostatic model assessment for insulin resistance. In addition, intention-to-treat, interim analysis and safety analysis will be performed. DISCUSSION: This double-blinded, randomised, clinical trial involves a multi-disciplinary approach and aims to explore the synergistic effects of the combination of semaglutide and empagliflozin. The results can provide important insights into mechanisms of GLP-1 receptor agonists and/or SGLT-2 inhibitors in patients with NAFLD and T2DM. TRIAL REGISTRATION: This study has been registered with Chinese Clinical Trial Registry (ChiCTR2300070674).