Study of a precise treatment protocol for patients with consciousness disorders based on the brain network analysis of functional magnetic resonance imaging.

Objective: How to conduct objective and accurate individualized assessments of patients with disorders of consciousness (DOC) and carry out precision rehabilitation treatment technology is a major rehabilitation problem that needs to be solved urgently. Methods: In this study, a multi-layer brain network was constructed based on functional magnetic resonance imaging (fMRI) to analyze the structural and functional brain networks of patients with DOC at different levels and to find regulatory targets (imaging markers) with recovery potential for DOC. Then repeated transcranial magnetic stimulation (rTMS) was performed in DOC patients to clinically validate. Results: The brain network connectivity of DOC patients with different consciousness states is different, and the most obvious brain regions appeared in the olfactory cortex and precuneus. rTMS stimulation could effectively improve the consciousness level of DOC patients and stimulate the occipital lobe (specific regions found in this study) and the dorsolateral prefrontal cortex (DLPFC), and both parts had a good consciousness recovery effect. Conclusion: In clinical work, personalized stimulation regimen treatment combined with the brain network characteristics of DOC patients can improve the treatment effect.

Hepatocyte-derived Fetuin-A promotes alcohol-associated liver disease in mice by inhibiting autophagy-lysosome degradation of TLR and M2 macrophage polarization.

BACKGROUND: Alcohol-associated liver disease (ALD) is one of the most common chronic liver diseases worldwide. Fetuin-A (FetA) is a plasma glycoprotein closely related to fat accumulation in the liver. However, the role of FetA in ALD remains unclear. METHODS: Both National Institute on Alcohol Abuse and Alcoholism (NIAAA) model and ethanol (EtOH) treated cell were used in this study. The effect of FetA deficiency on the progression of ALD was analyzed and the underlying mechanism was explored. RESULTS: The expression of FetA was upregulated in the liver tissues of ethanol-fed mice and ALD patients, as well as in AML12 cells treated with ethanol. FetA deletion reduced hepatic steatosis, oxidative stress, and inflammation in ALD mice. Interestingly, the absence of FetA led to a reduction of TLR4 protein level in liver tissue of EtOH-fed mice, without a corresponding change of its mRNA level. Conversely, the administration of recombinant FetA elevated TLR4 protein level in ethanol-treated RAW264.7 cells. FetA knockout significantly impeded the polarization of M1 macrophage in vivo or in vitro. Mechanistically, FetA deficiency drived the autophagy-lysosomal degradation of TLR4, subsequently inhibiting the activation of NF-kB/NLRP3 inflammasome pathway. Furthermore, knockdown of FetA using an adeno-associated virus 8 (AAV8)-shRNA can effectively prevent the progression of ALD in mice. CONCLUSION: Our results indicate that inhibition of FetA reverses the progression of ALD in mice, implying that FetA can serve as a therapeutic target for the treatment of ALD.

FABP4 deficiency ameliorates alcoholic steatohepatitis in mice via inhibition of p53 signaling pathway.

Fatty acid-binding protein 4 (FABP4) plays an essential role in metabolism and inflammation. However, the role of FABP4 in alcoholic steatohepatitis (ASH) remains unclear. This study aimed to investigate the function and underlying mechanisms of FABP4 in the progression of ASH. We first obtained alcoholic hepatitis (AH) datasets from the National Center for Biotechnology Information-Gene Expression Omnibus database and conducted bioinformatics analysis to identify critical genes in the FABP family. We then established ASH models of the wild-type (WT) and Fabp4-deficient (Fabp4-/-) mice to investigate the role of FABP4 in ASH. Additionally, we performed transcriptional profiling of mouse liver tissue and analyzed the results using integrative bioinformatics. The FABP4-associated signaling pathway was further verified. FABP4 was upregulated in two AH datasets and was thus identified as a critical biomarker for AH. FABP4 expression was higher in the liver tissues of patients with alcoholic liver disease and ASH mice than in the corresponding control samples. Furthermore, the Fabp4-/- ASH mice showed reduced hepatic lipid deposition and inflammation compared with the WT ASH mice. Mechanistically, Fabp4 may be involved in regulating the p53 and sirtuin-1 signaling pathways, subsequently affecting lipid metabolism and macrophage polarization in the liver of ASH mice. Our results demonstrate that Fabp4 is involved in the progression of ASH and that Fabp4 deficiency may ameliorate ASH. Therefore, FABP4 may be a potential therapeutic target for ASH treatment.

A FAPα-activated MRI nanoprobe for precise grading diagnosis of clinical liver fibrosis.

Molecular imaging holds the potential for noninvasive and accurate grading of liver fibrosis. It is limited by the lack of biomarkers that strongly correlate with liver fibrosis grade. Here, we discover the grading potential of fibroblast activation protein alpha (FAPα) for liver fibrosis through transcriptional analysis and biological assays on clinical liver samples. The protein and mRNA expression of FAPα are linearly correlated with fibrosis grade (R2 = 0.89 and 0.91, respectively). A FAPα-responsive MRI molecular nanoprobe is prepared for quantitatively grading liver fibrosis. The nanoprobe is composed of superparamagnetic amorphous iron nanoparticles (AFeNPs) and paramagnetic gadoteric acid (Gd-DOTA) connected by FAPα-responsive peptide chains (ASGPAGPA). As liver fibrosis worsens, the increased FAPα cut off more ASGPAGPA, restoring a higher T1-MRI signal of Gd-DOTA. Otherwise, the signal remains quenched due to the distance-dependent magnetic resonance tuning (MRET) effect between AFeNPs and Gd-DOTA. The nanoprobe identifies F1, F2, F3, and F4 fibrosis, with area under the curve of 99.8%, 66.7%, 70.4%, and 96.3% in patients' samples, respectively. This strategy exhibits potential in utilizing molecular imaging for the early detection and grading of liver fibrosis in the clinic.

Neuronavigation combined with intraoperative ultrasound and intraoperative magnetic resonance imaging vs neuronavigation alone in diffuse glioma surgery.

OBJECTIVE: This study aimed to integrate intraoperative ultrasound (IUS) and magnetic resonance imaging (IMRI) with neuronavigation (NN) to create a multimodal surgical protocol for diffuse gliomas. Clinical outcomes were compared to the standard NN-guided protocol. METHODS: Adult patients with diffuse gliomas scheduled for gross total resection (GTR) were consecutively enrolled to undergo either NN-guided surgery (80 patients, July 2019-January 2022) or multimodal-integrated surgery (80 patients, February 2022-August 2023). The primary outcomes were the extent of resection (EOR) and GTR. Additional outcomes included operative time, blood loss, length of hospital stay, and patient survival. RESULTS: GTR was achieved in 69% of patients who underwent multimodal-integrated surgery, compared to 43% of those who received NN-guided surgery (P=0.002). Residual tumor was detected by IMRI in 53 patients (66%), and further GTR was achieved in 28 of these cases. The median EOR was 100% for the multimodal group and 95% for the NN-guided group (P=0.001), while the median operative time was 8 hours versus 5 hours (P<0.001). Neurological deficits, blood loss, and hospital stay durations were comparable between two groups. Multimodal-integrated surgery resulted in greater EOR and higher GTR rates in contrast-enhancing gliomas, gliomas in eloquent regions, and large gliomas (≥50mm). GTR in glioblastomas and other contrast-enhancing gliomas contributed to improved overall survival. CONCLUSIONS: Compared to standard NN-guided surgery, multimodal-integrated surgery using NN, IMRI, and IUS significantly increased the EOR and GTR rates for diffuse gliomas.

Preoperative patient-reported outcome measures predict minimal clinically important difference and patient-acceptable symptomatic state following arthroscopic Bankart repair.

Aims: The aims of this study were to validate the minimal clinically important difference (MCID) and patient-acceptable symptom state (PASS) thresholds for Western Ontario Shoulder Instability Index (WOSI), Rowe score, American Shoulder and Elbow Surgeons (ASES), and visual analogue scale (VAS) scores following arthroscopic Bankart repair, and to identify preoperative threshold values of these scores that could predict the achievement of MCID and PASS. Methods: A retrospective review was conducted on 131 consecutive patients with anterior shoulder instability who underwent arthroscopic Bankart repair between January 2020 and January 2023. Inclusion criteria required at least one episode of shoulder instability and a minimum follow-up period of 12 months. Preoperative and one-year postoperative scores were assessed. MCID and PASS were estimated using distribution-based and anchor-based methods, respectively. Receiver operating characteristic curve analysis determined preoperative patient-reported outcome measure thresholds predictive of achieving MCID and PASS. Results: MCID thresholds were determined as 169.6, 6.8, 7.2, and 1.1 for WOSI, Rowe, ASES, and VAS, respectively. PASS thresholds were calculated as ≤ 480, ≥ 80, ≥ 87, and ≤ 1 for WOSI, Rowe, ASES, and VAS, respectively. Preoperative thresholds of ≥ 760 (WOSI) and ≤ 50 (Rowe) predicted achieving MCID for WOSI score (p < 0.001). Preoperative thresholds of ≤ 60 (ASES) and ≥ 2 (VAS) predicted achieving MCID for VAS score (p < 0.001). A preoperative threshold of ≥ 40 (Rowe) predicted achieving PASS for Rowe score (p = 0.005). Preoperative thresholds of ≥ 50 (ASES; p = 0.002) and ≤ 2 (VAS; p < 0.001) predicted achieving PASS for the ASES score. Preoperative thresholds of ≥ 43 (ASES; p = 0.046) and ≤ 4 (VAS; p = 0.024) predicted achieving PASS for the VAS. Conclusion: This study defined MCID and PASS values for WOSI, Rowe, ASES, and VAS scores in patients undergoing arthroscopic Bankart repair. Higher preoperative functional scores may reduce the likelihood of achieving MCID but increase the likelihood of achieving the PASS. These findings provide valuable guidance for surgeons to counsel patients realistically regarding their expectations.

CCDC113 promotes colorectal cancer tumorigenesis and metastasis via TGF-ß signaling pathway.

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. Although CRC patients' survival is improved with surgical resection and immunotherapy, metastasis and recurrence remain major problems leading to poor prognosis. Therefore, exploring pathogenesis and identifying specific biomarkers are crucial for CRC early diagnosis and targeted therapy. CCDC113, a member of CCDC families, has been reported to play roles in ciliary assembly, ciliary activity, PSCI, asthma and early lung cancer diagnosis. However, the functions of CCDC113 in CRC still remain unclear. In this study, we find that CCDC113 is significantly highly expressed in CRC. High expression of CCDC113 is significantly correlated with CRC patients' poor prognosis. CCDC113 is required for CRC tumorigenesis and metastasis. RNA-seq and TCGA database analysis indicate that CCDC113 is positively correlated with TGF-ß signaling pathway. TGF-ß signaling pathway inhibitor galunisertib could reverse the increased proliferation and migration ability of CRC cells caused by CCDC113 overexpression in vitro and in vivo. These results indicate that CCDC113 promotes CRC tumorigenesis and metastasis via TGF-ß signaling pathway. In conclusion, it is the first time to explore the functions and mechanisms of CCDC113 in CRC tumorigenesis and metastasis. And CCDC113 may be a potential biomarker and therapeutic target for CRC intervention.

Effect of negative pressure wound therapy on the incidence of deep surgical site infections after orthopedic surgery: a meta-analysis and systematic review.

OBJECTIVE: This meta-analysis aimed to explore the impact of prophylactic negative pressure wound therapy (NPWT) on the occurrence of deep surgical site infections (SSIs) following orthopedic surgery. METHODS: A systematic search was conducted across Medline, Embase, Cochrane Library, and Web of Science databases for articles concerning NPWT in patients who underwent orthopedic surgery up to May 20, 2024. Using Stata 15.0, the combined odds ratios (ORs) were calculated with either a random-effects model or a fixed-effects model, depending on the heterogeneity values. RESULTS: From a total of 440 publications, studies that utilized NPWT as the experimental group and conventional dressings as the control group were selected to analyze their impact on SSIs. Ultimately, 32 studies met the inclusion criteria. These included 12 randomized controlled trials and 20 cohort studies, involving 7454 patients, with 3533 of whom received NPWT and 3921 of whom were treated with conventional dressings. The results of the meta-analysis demonstrated that the NPWT group had a lower incidence of deep SSIs in orthopedic surgeries than did the control group [OR 0.64, 95% CI (0.52, 0.80), P = 0.0001]. Subgroup analysis indicated a notable difference for trauma surgeries [OR 0.65, 95% CI (0.50, 0.83), P = 0.001], whereas joint surgeries [OR 0.65, 95% CI (0.38, 1.12), P = 0.122] and spine surgeries [OR 0.61, 95% CI (0.27, 1.35), P = 0.221] did not show significant differences. Additionally, when examined separately according to heterogeneity, trauma surgeries exhibited a significant difference [OR 0.50, 95% CI (0.31, 0.80), P = 0.004]. CONCLUSION: The results of our study indicate that the prophylactic use of NPWT reduces the incidence of deep SSIs following orthopedic trauma surgery when compared to the use of conventional dressings. We postulate that the prophylactic application of NPWT in patients at high risk of developing complications from bone trauma may result in improved clinical outcomes and an enhanced patient prognosis.

Incomplete Histologic Healing and Diminished Biomechanical Strength of Meniscus-Bone Interface After Medial Meniscus Posterior Root Transosseous Repair in a Goat Model.

PURPOSE: To enhance the understanding of histologic healing after repairing medial meniscal posterior root tears (MMPRTs) at an early stage, utilizing a goat model. METHODS: Eighteen adult goats, totaling 36 knee joints, were allocated into 3 groups (n = 12): sham group (Sham), root tear group (RT), and root tear with transosseous suture group (RTS). At 12- and 24-week intervals postsurgery, all the knees were harvested for imaging, macroscopic, histologic, and biomechanical assessments. RESULTS: The intact root served as a meniscus-bone interface that connected the tibial and circular fibers of the meniscus with a bony insertion and a root-meniscus transition. A direct fibrous connection was displayed at the bony insertion proximal to the synovium in the RTS group, while the remaining regions of the root displayed indirect fibrous healing. The healing in the RT group was disjointed and reminiscent of scar tissue. The RTS group exhibited a more pronounced coronal extrusion compared to the Sham group (0.42 ± 0.09 vs 0.19 ± 0.02, P = .0012) but was improved relative to that of the RT group (0.49 ± 0.02, P = .0028). The failure load and stiffness of the RTS group were notably higher than those of the RT group, with a strength of 42.67% and a stiffness of 83.75% of the intact root. All the samples ruptured at the root-meniscus transitions. CONCLUSIONS: The incomplete healing may be attributed to the histologic factors underlying the low healing rate and persistent medial meniscal extrusion. Notably, the region attached to the posterior cruciate ligament exhibited superior healing compared to other regions of the bony insertion in the repaired group. Conversely, the root-meniscus transition displayed discontinuity, representing a mechanical weakness in the healing process. CLINICAL RELEVANCE: Modifications of bone tunnel positioning and suture placement could be undertaken in subsequent studies to enhance the healing of the root-meniscus transition.

Research progress on the immunological functions of Piezo1 a receptor molecule that responds to mechanical force.

The human immune system is capable of defending against, monitoring, and self-stabilizing various immune cells. Differentiation, proliferation, and development of these cells are regulated by biochemical signals. Moreover, biophysical signals, such as mechanical forces, have been found to affect immune cell function, thus introducing a new area of immunological research. Piezo1, a mechanically sensitive ion channel, was awarded the Nobel Prize for Physiology and Medicine in 2021. This channel is present on the surface of many cells, and when stimulated by mechanical force, it controls calcium (Ca2+) inside the cells, leading to changes in downstream signals and thus regulating cell functions. Piezo1 is also expressed in various innate and adaptive immune cells and plays a major role in the immune function. In this review, we will explore the physiological functions and regulatory mechanisms of Piezo1 and its impact on innate and adaptive immunity. This may offer new insights into diagnostics and therapeutics for the prevention and treatment of diseases and surgical infections.

Inflammatory bowel disease and osteoporosis: Common genetic effects, pleiotropy, and causality.

INTRODUCTION: Previous studies have shown that inflammatory bowel disease (IBD) is associated with osteoporosis (OP) and bone mineral density (BMD), but the underlying genetic mechanisms are unclear. Our study wanted to explore the genetic and causal relationship between IBD and OP. MATERIALS AND METHODS: Based on large-scale genome-wide association summary statistics and individual-level datasets (i.e., the UK Biobank), this study performed linkage disequilibrium score regression (LDSC), pleiotropic analysis under the composite null hypothesis (PLACO), and Mendelian randomization (MR) analyses to explore the genetic association, the pleiotropic genes and the causal relationship between IBD and BMD. RESULTS: LDSC revealed significant genetic correlations between IBD and BMD (e.g., forearm BMD (rg = -0.3479, P = 0.019) and femoral neck BMD (rg = -0.1335, P = 0.0307). PLACO identified 14 overlapping pleiotropic loci, 1 shared risk gene (CDYL), and multiple shared pathways, revealing possible mechanisms for IBD and OP. MR analysis demonstrated a causal association between IBD and BMD. CONCLUSIONS: Our study indicates that IBD may increase the risk of OP and reveals a complex genetic mechanism linking IBD and the risk of osteoporosis, which has important implications for diagnosing and treating IBD and OP.

Clinical features, MRI, molecular alternations, and prognosis of astrocytoma based on WHO 2021 classification of central nervous system tumors: A single-center retrospective study.

BACKGROUND: The diagnosis of glioma has advanced since the release of the WHO 2021 classification with more molecular alterations involved in the integrated diagnostic pathways. Our study aimed to present our experience with the clinical features and management of astrocytoma, IDH mutant based on the latest WHO classification. METHODS: Patients diagnosed with astrocytoma, IDH-mutant based on the WHO 5th edition classification of CNS tumors at our center from January 2009 to January 2022 were included. Patients were divided into WHO 2-3 grade group and WHO 4 grade group. Integrate diagnoses were retrospectively confirmed according to WHO 2016 and 2021 classification. Clinical and MRI characteristics were reviewed, and survival analysis was performed. RESULTS: A total of 60 patients were enrolled. 21.67% (13/60) of all patients changed tumor grade from WHO 4th edition classification to WHO 5th edition. Of these, 21.43% (6/28) of grade II astrocytoma and 58.33% (7/12) of grade III astrocytoma according to WHO 4th edition classification changed to grade 4 according to WHO 5th edition classification. Sex (p = 0.042), recurrent glioma (p = 0.006), and Ki-67 index (p < 0.001) of pathological examination were statistically different in the WHO grade 2-3 group (n = 27) and WHO grade 4 group (n = 33). CDK6 (p = 0.004), FGFR2 (p = 0.003), and MYC (p = 0.004) alterations showed an enrichment in the WHO grade 4 group. Patients with higher grade showed shorter mOS (mOS = 75.9 m, 53.6 m, 26.4 m for grade 2, 3, and 4, respectively, p = 0.01). CONCLUSIONS: Patients diagnosed as WHO grade 4 according to the 5th edition WHO classification based on molecular alterations are more likely to have poorer prognosis. Therefore, treatment should be tailored to their individual needs. Further research is needed for the management of IDH-mutant astrocytoma is needed in the future.

The molecular signature and prognosis of glioma with preoperative intratumoral hemorrhage: a retrospective cohort analysis.

BACKGROUND: Intratumoral hemorrhage, though less common, could be the first clinical manifestation of glioma and is detectable via MRI; however, its exact impacts on patient outcomes remain unclear and controversial. The 2021 WHO CNS 5 classification emphasised genetic and molecular features, initiating the necessity to establish the correlation between hemorrhage and molecular alterations. This study aims to determine the prevalence of intratumoral hemorrhage in glioma subtypes and identify associated molecular and clinical characteristics to improve patient management. METHODS: Integrated clinical data and imaging studies of patients who underwent surgery at the Department of Neurosurgery at Peking Union Medical College Hospital from January 2011 to January 2022 with pathological confirmation of glioma were retrospectively reviewed. Patients were divided into hemorrhage and non-hemorrhage groups based on preoperative magnetic resonance imaging. A comparison and survival analysis were conducted with the two groups. In terms of subgroup analysis, we classified patients into astrocytoma, IDH-mutant; oligodendroglioma, IDH-mutant, 1p/19q-codeleted; glioblastoma, IDH-wildtype; pediatric-type gliomas; or circumscribed glioma using integrated histological and molecular characteristics, according to WHO CNS 5 classifications. RESULTS: 457 patients were enrolled in the analysis, including 67 (14.7%) patients with intratumoral hemorrhage. The hemorrhage group was significantly older and had worse preoperative Karnofsky performance scores. The hemorrhage group had a higher occurrence of neurological impairment and a higher Ki-67 index. Molecular analysis indicated that CDKN2B, KMT5B, and PIK3CA alteration occurred more in the hemorrhage group (CDKN2B, 84.4% vs. 62.2%, p = 0.029; KMT5B, 25.0% vs. 8.9%, p = 0.029; and PIK3CA, 81.3% vs. 58.5%, p = 0.029). Survival analysis showed significantly worse prognoses for the hemorrhage group (hemorrhage 18.4 months vs. non-hemorrhage 39.1 months, p = 0.01). In subgroup analysis, the multivariate analysis showed that intra-tumoral hemorrhage is an independent risk factor only in glioblastoma, IDH-wildtype (162 cases of 457 overall, HR = 1.72, p = 0.026), but not in other types of gliomas. The molecular alteration of CDK6 (hemorrhage group p = 0.004, non-hemorrhage group p < 0.001), EGFR (hemorrhage group p = 0.003, non-hemorrhage group p = 0.001), and FGFR2 (hemorrhage group p = 0.007, non-hemorrhage group p = 0.001) was associated with shorter overall survival time in both hemorrhage and non-hemorrhage groups. CONCLUSIONS: Glioma patients with preoperative intratumoral hemorrhage had unfavorable prognoses compared to their nonhemorrhage counterparts. CDKN2B, KMT5B, and PIK3CA alterations were associated with an increased occurrence of intratumoral hemorrhage, which might be future targets for further investigation of intratumoral hemorrhage.

Clinical application of intraoperative ultrasound superb microvascular imaging in brain tumors resections: contributing to the achievement of total tumoral resection.

BACKGROUND: To investigate whether the intraoperative superb microvascular imaging(SMI) technique helps evaluate lesion boundaries compared with conventional grayscale ultrasound in brain tumor surgery and to explore factors that may be associated with complete radiographic resection. METHODS: This study enrolled 57 consecutive brain tumor patients undergoing surgery. During the operation, B-mode and SMI ultrasound evaluated the boundaries of brain tumors. MRI before and within 48h after surgery was used as the gold standard to evaluate gross-total resection(GTR). The ultrasound findings and GTR results were analyzed to determine the imaging factors related to GTR. RESULTS: A total of 57 patients were enrolled in the study, including 32 males and 25 females, with an average age of 53.4 ± 14.1 years old(range 19 ~ 80). According to the assessment criteria of MRI, before and within 48 h after the operation, 37(63.9%) cases were classified as GTR, and 20(35.1%) cases were classified as GTR. In comparing tumor interface definition between B-mode and SMI mode, SMI improved HGG boundary recognition in 5 cases(P = 0.033). The results showed that the tumor size ≥ 5 cm and unclear ultrasonic boundary were independent risk factors for nGTR (OR>1, P<0.05). CONCLUSIONS: As an innovative intraoperative doppler technique in neurosurgery, SMI can effectively demarcate the tumor's boundary and help achieve GTR as much as possible.

RNF144A-AS1 stabilizes TAF15 and promotes malignant biological behaviors of skin cutaneous melanoma.

LncRNAs have been demonstrated to regulate biological processes in malignant tumors. In our previous study, we identified the immune-related LncRNA RNF144A-AS1 as a potential regulator in SKCM. However, its precise function and regulatory mechanism remain unclear. In this study, we observed upregulation of RNF144A-AS1 in SKCM and found that knockdown of RNF144A-AS1 suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition abilities of melanoma cells. Mechanistically, as a high-risk prognostic factor, RNF144A-AS1 regulated biological processes of SKCM by interacting with TAF15 through an RNA-binding protein-dependent (RBP-dependent) manner. Furthermore, we confirmed that TAF15 activated downstream transcriptional regulation of YAP1 to modulate malignant behaviors in melanoma cells. In vivo experiments revealed that knockdown of RNF144A-AS1 inhibited tumorigenic capacity of melanoma cells and exhibited promising therapeutic effects. Collectively, these findings highlight the significance of the RNF144A-AS1/TAF15/YAP1 axis in promoting malignant behaviors in SKCM and provide novel insights into potential prognostic biomarkers and therapeutic targets for this disease.

Distinct drivers of bacterial community assembly processes in riverine islands in the middle and lower reaches of the Yangtze River.

Riverine islands are widespread alluvium wetlands developed in large rivers, and bacterial communities are crucial to their ecological function, yet their assembly processes are rarely addressed. The ecosystem services provided by the middle and the lower Yangtze are primarily threatened by pollution discharge from agricultural land use, and resource overutilization (e.g., embankments), respectively. Here, we assessed bacterial community assembly processes and their drivers within riverine islands in the middle Yangtze River (MR islands) and those in the lower reach (LR islands). A significant distance-decay relationship was observed, although the turnover rate was lower than that of the terrestrial ecosystem with less connectivity. Deterministic and stochastic processes jointly shaped community patterns, and the influence of stochastic increased from 26% in MR islands to 59% for those in LR islands. Meanwhile, the bacterial community in MR islands was controlled more by inorganic nitrogen availability, whereas those in LR islands were governed by pH and EC, although those factors explained a limited fraction of variation in the bacterial community. Potential indicator taxa (affiliated with Nocardioides and Lysobacter) characterized the waterway transport pollution. Overall, our study demonstrated that bacterial community dissimilarity and the importance of dispersal limitation increased concurrently along the flow direction, while distinct local factors further determined bacterial community compositions by selecting habitat-specificity taxa and particularly metabolism function. These findings enhanced our understanding of the mechanisms driving changes in bacterial communities of riverine islands subject to increased anthropogenic impacts.IMPORTANCERivers are among the most threatened ecosystems globally and face multiple stressors related to human activity. However, linkages between microbial diversity patterns and assembly processes in rivers remain unclear, especially in riverine islands developed in large rivers. Our findings reveal that distinct factors result in divergent bacterial community compositions and functional profiles in the riverine islands in the middle Yangtze and those in the lower Yangtze, with substantial differentiation in deterministic and stochastic processes that jointly contribute to bacterial community assemblages. Additionally, keystone species may play important metabolic roles in coping with human-related disturbances. This study provides an improved understanding of relationships between microbial diversity patterns and ecosystem functions under environmental changes in large river ecosystems.

Damage-Tolerant and Self-Repairing Web-Like Borate Type Binder Enable Stable Operation of Efficient Si-Based Anodes.

Novel binder designs are shown to be fruitful in improving the electrochemical performance of silicon (Si)-based anodes. However, issues with mechanical damage from dramatic volume change and poor lithium-ion (Li+) diffusion kinetics in Si-based materials still need to be addressed. Herein, an aqueous self-repairing borate-type binder (SBG) with a web-like architecture and high ionic conductivity is designed for Si and SiO electrodes. The 3D web-like architecture of the SBG binder enables uniform stress distribution, while its self-repairing ability promotes effective stress dissipation and mechanical damage repair, thereby enhancing the damage tolerance of the electrode. The tetracoordinate boron ions ( - BO 4 - $ - {\mathrm{BO}}_4^ - $ ) in the SBG binder boosts the Li transportation kinetics of Si-based electrodes. Based on dynamic covalent and ionic conductive boronic ester bonds, the diverse requirements of the binder, including uniform stress distribution, self-repairing ability, and high ionic conductivity, can be met by simple components. Consequently, the proposed straightforward multifunction design strategy for binders based on dynamic boron chemistry provides valuable insights into fabricating high-performance Si-based anodes.

Artificial neural network identified a 20-gene panel in predicting immunotherapy response and survival benefits after anti-PD1/PD-L1 treatment in glioblastoma patients.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are a promising immunotherapy approach, but glioblastoma clinical trials have not yielded satisfactory results. OBJECTIVE: To screen glioblastoma patients who may benefit from immunotherapy. METHODS: Eighty-one patients receiving anti-PD1/PD-L1 treatment from a large-scale clinical trial and 364 patients without immunotherapy from The Cancer Genome Atlas (TCGA) were included. Patients in the ICI-treated cohort were divided into responders and nonresponders according to overall survival (OS), and the most critical responder-relevant features were screened using random forest (RF). We constructed an artificial neural network (ANN) model and verified its predictive value with immunotherapy response and OS. RESULTS: We defined two groups of ICI-treated glioblastoma patients with large differences in survival benefits as nonresponders (OS ≤6 months, n = 18) and responders (OS ≥17 months, n = 8). No differentially mutated genes were observed between responders and nonresponders. We performed RF analysis to select the most critical responder-relevant features and developed an ANN with 20 input variables, five hidden neurons and one output neuron. Receiver operating characteristic analysis and the DeLong test demonstrated that the ANN had the best performance in predicting responders, with an AUC of 0.97. Survival analysis indicated that ANN-predicted responders had significantly better OS rates than nonresponders. CONCLUSION: The 20-gene panel developed by the ANN could be a promising biomarker for predicting immunotherapy response and prognostic benefits in ICI-treated GBM patients and may guide oncologists to accurately select potential responders for the preferential use of ICIs.

Lewis Acid Catalyzed Cycloaddition of Bicyclobutanes with Ynamides for the Synthesis of Polysubstituted 2-Amino-bicyclo[2.1.1]hexenes.

Synthesis of bicyclic scaffolds has gained significant attention in drug discovery due to their potential to mimic benzene bioisosteres. Here, we present a mild and scalable Sc(OTf)3-catalyzed [3+2] cycloaddition of bicyclo[1.1.0]butanes (BCBs) with ynamides, yielding a diverse array of polysubstituted 2-amino-bicyclo[2.1.1]hexenes in good to excellent yields. These products offer valuable starting materials for the construction of novel functionalized bicyclo[1.1.0]butanes. Preliminary mechanistic studies indicate that the reaction involves a nucleophilic addition of ynamides to bicyclo[1.1.0]butanes, followed by an intramolecular cyclization of in situ generated enolate and keteniminium ion. We expect that these findings will encourage utilization of complex bioisosteres and foster further investigation into BCB-based cycloaddition chemistry.

Clinical roles of EGFR amplification in diffuse gliomas: a real-world study using the 2021 WHO classification of CNS tumors.

Background: The 2021 World Health Organization Classification of Central Nervous System Tumors updates glioma subtyping and grading system, and incorporates EGFR amplification (Amp) as one of diagnostic markers for glioblastoma (GBM). Purpose: This study aimed to describe the frequency, clinical value and molecular correlation of EGFR Amp in diffuse gliomas based on the latest classification. Methods: We reviewed glioma patients between 2011 and 2022 at our hospital, and included 187 adult glioma patients with available tumor tissue for detection of EGFR Amp and other 59 molecular markers of interest. Clinical, radiological and pathological data was analyzed based on the status of EGFR Amp in different glioma subtypes. Results: 163 gliomas were classified as adult-type diffuse gliomas, and the number of astrocytoma, oligodendroglioma and GBM was 41, 46, and 76. EGFR Amp was more common in IDH-wildtype diffuse gliomas (66.0%) and GBM (85.5%) than IDH-mutant diffuse gliomas (32.2%) and its subtypes (astrocytoma, 29.3%; oligodendroglioma, 34.8%). EGFR Amp did not stratify overall survival (OS) in IDH-mutant diffuse gliomas and astrocytoma, while was significantly associated with poorer OS in IDH-wildtype diffuse gliomas, histologic grade 2 and 3 IDH-wildtype diffuse astrocytic gliomas and GBM. Conclusion: Our study validated EGFR Amp as a diagnostic marker for GBM and still a useful predictor for shortened OS in this group.