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The integrated application of artificial intelligence (AI) and digital pathology (DP) technology has opened new avenues for advancements in oncology and molecular pathology. Consequently, studies in renal cell carcinoma (RCC) have emerged, highlighting potential in histological subtype classification, molecular aberration identification, and outcome prediction by extracting high-throughput features. However, reviews of these studies are still rare. To address this gap, we conducted a thorough literature review on DP and AI applications in RCC through database searches. Notably, we found that AI models based on deep learning achieved area under the curve (AUC) of over 0.93 in subtype classification, 0.89-0.96 in grading of clear cell RCC, 0.70-0,89 in molecular prediction, and over 0.78 in survival prediction. This review finally discussed the current state of researches and potential future directions.

Proximal humerus fractures (PHFs) are common in the elderly and usually involve defects in the medial column.The current standard for medial column reconstruction is a lateral locking plate (LLP) in combination with either an intramedullary fibula support or an autogenous fibula graft. However, autogenous fibula graft can lead to additional trauma for patients and allogeneic fibular graft can increase patients’ economic burden and pose risks of infection and disease transmission. The primary objective of this study was to introduce and assess a novel “Sandwich” fixation technique and compare its biomechanical properties to the traditional fixation methods for PHFs. In this study, we established finite element models of two different internal fixation methods: LLP-intramedullary reconstruction plate with bone cement (LLP-IRPBC) and LLP-intramedullary fibula segment (LLP-IFS). The biomechanical properties of the two fixation methods were evaluated by applying axial, adduction, abduction, torsional loads and screw extraction tests to the models. These FEA results were subsequently validated through a series of biomechanical experiments. Under various loading conditions such as axial, adduction, abduction, and rotation, the LLP-IRPBC group consistently demonstrated higher structural stiffness and less displacement compared to the LLP-IFS group, regardless of whether the bone was in a normal (Nor) or osteoporotic (Ost) state. Under axial, abduction and torsional loads, the maximum stress on LLPs of LLP-IRPBC group was lower than that of LLP-IFS group, while under adduction load, the maximum stress on LLPs of LLP-IRPBC group was higher than that of LLP-IFS group under Ost condition, and almost the same under Nor condition. The screw-pulling force in the LLP-IRPBC group was 1.85 times greater than that of the LLP-IFS group in Nor conditions and 1.36 times greater in Ost conditions. Importantly, the results of the biomechanical experiments closely mirrored those obtained through FEA, confirming the accuracy and reliability of FEA. The novel “Sandwich” fixation technique appears to offer stable medial support and rotational stability while significantly enhancing the strength of the fixation screws. This innovative approach represents a promising strategy for clinical treatment of PHFs.

Background and aimsIn recent years, the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and colorectal cancer (CRC) or colorectal adenoma (CRA) has gained widespread attention. Previous meta-analyses on this subject either incorporated numerous cross-sectional studies, which were susceptible to bias, or concentrated solely on a restricted number of cohort studies. Moreover, with the release of a substantial number of high-quality cohort studies on this subject in the past two years, the findings continue to be debated and contradictory. Therefore, we conducted an updated systematic review and meta-analysis of cohort studies to quantitatively evaluate the magnitude of the association between them.MethodsComprehensive searches of PubMed, Web of Science, and Embase were conducted without language restrictions from the time of their creation up to December, 2023. The pooled hazard ratios (HRs) with 95% confidence interval (CIs) were calculated by the generic inverse variance based on the random-effects model. Moreover, subgroup and sensitivity analyses were performed.ResultsA total of 15 cohort studies were analyzed in this meta-analysis, which included 9,958,412 participants. The meta-analysis of 13 cohort studies showed that MASLD was linked to a higher risk of CRC (HR=1.25, 95% CI: 1.15-1.36, P < 0.00001). Additionally, further subgroup analysis indicated that the combined HR remained consistent regardless of the study location, nomenclature of fatty liver disease (FLD), confirmation methods for FLD, sample size, follow-up time, and study quality. Furthermore, the meta-analysis of four cohort studies demonstrated that MASLD was correlated with an increased risk of CRA (HR=1.38, 95% CI: 1.17-1.64, P = 0.0002). The sensitivity analysis results further validated the robustness of the aboved findings.ConclusionThe results of our meta-analysis indicated that MASLD was associated with an increased risk of incident CRC/CRA. In the future, it is necessary to conduct more prospective cohort studies to thoroughly assess potential confounding factors, particularly in individuals from Europe and North America. Furthermore, related mechanism studies should be conducted to enhance our understanding of the link between MASLD and CRC/CRA.Systematic review registrationOpen Science Framework registries (https://osf.io/m3p9k).

BackgroundMultiple myeloma (MM) exhibits considerable heterogeneity in treatment responses and survival rates, even when standardized care is administered. Ongoing efforts are focused on developing prognostic models to predict these outcomes more accurately. Recently, neutrophil extracellular traps (NETs) have emerged as a potential factor in MM progression, sparking investigation into their role in prognostication.MethodsIn this study, a multi-gene risk scoring model was constructed using the intersection of NTEs and differentially expressed genes (DEGs), applying the least absolute shrinkage and selection operator (LASSO) Cox regression model. A nomogram was established, and the prognostic model’s effectiveness was determined via Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). The ESTIMATE algorithm and immune-related single-sample gene set enrichment analysis (ssGSEA) were employed to evaluate the level of immune infiltration. The sensitivity of chemotherapy drugs was assessed using the Genomics of Drug Sensitivity in Cancer (GDSC) database. Ultimately, the presence of the detected genes was confirmed through quantitative real-time polymerase chain reaction (qRT-PCR) analysis in MM cell specimens.Results64 NETs-DEGs were yielded, and through univariate Cox regression and LASSO regression analysis, we constructed a risk score composed of six genes: CTSG, HSPE1, LDHA, MPO, PINK1, and VCAM1. MM patients in three independent datasets were classified into high- and low-risk groups according to the risk score. The overall survival (OS) of patients in the high-risk group was significantly reduced compared to the low-risk group. Furthermore, the risk score was an independent predictive factor for OS. In addition, interactions between the risk score, immune score, and immune cell infiltration were investigated. Further analysis indicated that patients in the high-risk group were more sensitive to a variety of chemotherapy and targeted drugs, including bortezomib. Moreover, the six genes provided insights into the progression of plasma cell disorders.ConclusionThis study offers novel insights into the roles of NETs in prognostic prediction, immune status, and drug sensitivity in MM, serving as a valuable supplement and enhancement to existing grading systems.

BackgroundPueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) and Schisandra sphenanthera Rehder & E.H. Wilson are traditional edible and medicinal hepatoprotective botanical drugs. Studies have shown that the combination of two botanical drugs enhanced the effects of treating acute liver injury (ALI), but the synergistic effect and its action mechanisms remain unclear. This study aimed to investigate the synergistic effect and its mechanism of the combination of Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) (PM) and Schisandra sphenanthera Rehder & E.H. Wilson (SS) in the treatment of ALI.MethodsHigh performance liquid chromatography (HPLC) were utilized to conduct the chemical interaction analysis. Then the synergistic effects of botanical hybrid preparation of PM-SS (BHP PM-SS) against ALI were comprehensively evaluated by the CCl4 induced ALI mice model. Afterwards, symptom-oriented network pharmacology, transcriptomics and metabolomics were applied to reveal the underlying mechanism of action. Finally, the key target genes were experimentally by RT-qPCR.ResultsChemical analysis and pharmacodynamic experiments revealed that BHP PM-SS was superior to the single botanical drug, especially at 2:3 ratio, with a better dissolution rate of active ingredients and synergistic anti-ALI effect. Integrated symptom-oriented network pharmacology combined with transcriptomics and metabolomics analyses showed that the active ingredients of BHP PM-SS could regulate Glutathione metabolism, Pyrimidine metabolism, Arginine biosynthesis and Amino acid sugar and nucleotide sugar metabolism, by acting on the targets of AKT1, TNF, EGFR, JUN, HSP90AA1 and STAT3, which could be responsible for the PI3K-AKT signaling pathway, MAPK signaling pathway and Pathway in cancer to against ALI.ConclusionOur study has provided compelling evidence for the synergistic effect and its mechanism of the combination of BHP PM-SS, and has contributed to the development and utilization of BHP PM-SS dietary supplements.

BackgroundClassical biomarkers have been used to classify clear cell renal cell carcinoma (ccRCC) patients in a variety of ways, and emerging evidences have indicated that cuproptosis is closely related to mitochondrial metabolism, thereby accelerating the development and progression of ccRCC. Nevertheless, the specific relationship between cuproptosis and the prognosis and treatment of ccRCC remains unclear.MethodsWe comprehensively integrated several ccRCC patient datasets into a large cohort. Following that, we systematically analyzed multi-omics data to demonstrate the differences between two cuproptosis clusters.ResultsWe identified two cuproptosis clusters in ccRCC patients. Among the two clusters, cluster 1 patients showed favorable prognosis. We then confirmed the significant differences between the two clusters, including more typical cancer hallmarks were enriched in cluster 2 patients; cluster 2 patients were more susceptible to develop mutations and had a lower level of gistic score and mRNAsi. Importantly, both Tumor Immune Dysfunction and Exclusion analysis and subclass mapping algorithm showed that cuproptosis 1 patients were more susceptible to be responded to immunotherapy. In addition, a prognostic signature was successfully developed and also showed prominent predictive power in response to immunotherapy.ConclusionAs a result of our findings, we were able to classify ccRCC patients according to cuproptosis in a novel way. By constructing the cuproptosis clusters and developing the signature, patients with ccRCC could have a more accurate prognosis prediction and better immunotherapy options.

As important organelles of energetic and metabolism, changes in the dynamic state of mitochondria affect the homeostasis of cellular metabolism. Mitochondrial dynamics include mitochondrial fusion and mitochondrial fission. The former is coordinated by mitofusin-1 (Mfn1), mitofusin-2 (Mfn2), and optic atrophy 1 (Opa1), and the latter is mediated by dynamin related protein 1 (Drp1), mitochondrial fission 1 (Fis1) and mitochondrial fission factor (MFF). Mitochondrial fusion and fission are generally in dynamic balance and this balance is important to preserve the proper mitochondrial morphology, function and distribution. Diabetic conditions lead to disturbances in mitochondrial dynamics, which in return causes a series of abnormalities in metabolism, including decreased bioenergy production, excessive production of reactive oxygen species (ROS), defective mitophagy and apoptosis, which are ultimately closely linked to multiple chronic complications of diabetes. Multiple researches have shown that the incidence of diabetic complications is connected with increased mitochondrial fission, for example, there is an excessive mitochondrial fission and impaired mitochondrial fusion in diabetic cardiomyocytes, and that the development of cardiac dysfunction induced by diabetes can be attenuated by inhibiting mitochondrial fission. Therefore, targeting the restoration of mitochondrial dynamics would be a promising therapeutic target within type II diabetes (T2D) and its complications. The molecular approaches to mitochondrial dynamics, their impairment in the context of T2D and its complications, and pharmacological approaches targeting mitochondrial dynamics are discussed in this review and promise benefits for the therapy of T2D and its comorbidities.

Introduction: Sanjin tablets (SJT) are a well-known Chinese patent drug that have been used to treat urinary tract infections (UTIs) for the last 40 years. The drug consists of five herbs, but only 32 compounds have been identified, which hinders the clarification of its effective substances and mechanism.Methods: The chemical constituents of SJT and their effective substances and functional mechanism involved in the treatment of UTIs were investigated by using high performance liquid chromatography-electrospray ionization-ion trap-time of flight-mass spectrometry (HPLC-ESI-IT-TOF-MSn), network pharmacology, and molecular docking.Results: A total of 196 compounds of SJT (SJT-MS) were identified, and 44 of them were unequivocally identified by comparison with the reference compounds. Among 196 compounds, 13 were potential new compounds and 183 were known compounds. Among the 183 known compounds, 169 were newly discovered constituents of SJT, and 93 compounds were not reported in the five constituent herbs. Through the network pharmacology method, 119 targets related to UTIs of 183 known compounds were predicted, and 20 core targets were screened out. Based on the “compound–target” relationship analysis, 94 compounds were found to act on the 20 core targets and were therefore regarded as potential effective compounds. According to the literature, 27 of the 183 known compounds were found to possess antimicrobial and anti-inflammatory activities and were verified as effective substances, of which 20 were first discovered in SJT. Twelve of the 27 effective substances overlapped with the 94 potential effective compounds and were determined as key effective substances of SJT. The molecular docking results showed that the 12 key effective substances and 10 selected targets of the core targets have good affinity for each other.Discussion: These results provide a solid foundation for understanding the effective substances and mechanism of SJT.

BackgroundMultiple myeloma (MM) is a highly malignant hematological tumor with a poor overall survival (OS). Due to the high heterogeneity of MM, it is necessary to explore novel markers for the prognosis prediction for MM patients. Ferroptosis is a form of regulated cell death, playing a critical role in tumorigenesis and cancer progression. However, the predictive role of ferroptosis-related genes (FRGs) in MM prognosis remains unknown.MethodsThis study collected 107 FRGs previously reported and utilized the least absolute shrinkage and selection operator (LASSO) cox regression model to construct a multi-genes risk signature model upon FRGs. The ESTIMATE algorithm and immune-related single-sample gene set enrichment analysis (ssGSEA) were carried out to evaluate immune infiltration level. Drug sensitivity was assessed based on the Genomics of Drug Sensitivity in Cancer database (GDSC). Then the synergy effect was determined with Cell counting kit-8 (CCK-8) assay and SynergyFinder software.ResultsA 6-gene prognostic risk signature model was constructed, and MM patients were divided into high and low risk groups. Kaplan-Meier survival curves showed that patients in the high risk group had significantly reduced OS compared with patients in the low risk group. Besides, the risk score was an independent predictor for OS. Receiver operating characteristic (ROC) curve analysis confirmed the predictive capacity of the risk signature. Combination of risk score and ISS stage had better prediction performance. Enrichment analysis revealed immune response, MYC, mTOR, proteasome and oxidative phosphorylation were enriched in high risk MM patients. We found high risk MM patients had lower immune scores and immune infiltration levels. Moreover, further analysis found that MM patients in high risk group were sensitive to bortezomib and lenalidomide. At last, the results of the in vitro experiment showed that ferroptosis inducers (RSL3 and ML162) may synergistically enhance the cytotoxicity of bortezomib and lenalidomide against MM cell line RPMI-8226.ConclusionThis study provides novel insights into roles of ferroptosis in MM prognosis prediction, immune levels and drug sensitivity, which complements and improves current grading systems.

Gestational diabetes mellitus (GDM) is a metabolic disease with an increasing annual incidence. Our previous observational study found that pregnant women with gestational diabetes had mild cognitive decline, which may be related to methylglyoxal (MGO). This study aimed to investigate whether labor pain aggravates the increase in MGO and explored the protective effect of epidural analgesia on metabolism in pregnant women with GDM based on solid-phase microextraction gas chromatography/mass spectrometry (SPME/GC-MS). Pregnant women with GDM were divided into a natural birth group (ND group, n = 30) and epidural analgesia group (PD group, n = 30). After fasting for ≥ 10 h overnight, venous blood samples were collected pre- and post-delivery to detect MGO, interleukin-6 (IL-6), and 8-epi-prostaglandin F2 alpha (8-iso-PGF2α) by ELISA. Serum samples were analyzed for volatile organic compounds (VOCs) using SPME-GC-MS. MGO, IL-6, and 8-iso-PGF2α levels in the ND group increased significantly post-delivery (P < 0.05) and were significantly higher in this group than the levels in the PD group (P < 0.05). Compared to the PD group, VOCs in the ND group increased significantly post-delivery. Further results indicated that propionic acid may be associated with metabolic disorders in pregnant women with GDM. Epidural analgesia can effectively improve the metabolism and immune function in pregnant women with GDM.

This paper proposes an improved bacterial foraging algorithm for electrical load distribution to impro-ve power plants’ efficiency and reduce energy consumption costs. In the chemotaxis stage, the adaptive step size is introduced to accelerate the random search speed compared with the traditional algorithm. In the replication stage, a hybrid crisscross operator is proposed to replace the traditional binary replication method in the algorithm to ensure the diversity of the population and improve the efficiency of the algorithm. The adaptive dynamic probability is used instead of the initial fixed probability to improve the global search performance of the algorithm. The mathematical model of electrical load distribution in a natural power plant is established, and the improved bacterial foraging algorithm is used to solve the model. Through comparative analysis of two power plant unit experiments, it is proved that the results of the improved algorithm can reduce 3.671% and 1.06% respectively compared with the particle swarm optimization algorithm, and 7.26% and 1.37% respectively compared with the traditional bacterial foraging algorithm, which can significantly reduce the coal consumption of the power plant.

PurposeThe aim of present study is to evaluate the femoral head bone quality by Hounsfield units and its relationship to the occurrence of implant failure for intertrochanteric fractures after intramedullary nail fixation.MethodsThis retrospective study assessed 160 intertrochanteric fractures treated with intramedullary fixation. Patients with and without implant failure were divided into failure and control groups, respectively. The demographic information, femoral head Hounsfield unit (HU) value, the reduction quality, status of posteromedial support and position of the screw/blade were collected and compared. The logistic regression analyses were performed to evaluate risk factors of implant failure in intertrochanteric fractures after intramedullary nail fixation.ResultsOf the patients, 15 (9.38%) suffered from implant failure after intramedullary fixation. The mean HU value of femoral head was much lower in the failure group than the control group (133.25 ± 34.10 vs. 166.12 ± 42.68, p = 0.004). And the univariate analyses showed that A3 fracture and poor reduction quality were associated with implant failure (p

BackgroundHypertension remains a challenging public health problem worldwide, and adrenal gland-related diseases are one class of the major causes for secondary hypertension. Among them, one relatively rare pattern is adrenal hyperplastic hypertension caused by adrenal medullary hyperplasia (AMH), leading to excessive secretion of autonomic catecholamine. Given that the pathological changes of adrenal medulla are not well correlated to the onset and even severity of secondary hypertension, the molecular basis why some AMH patients are accompanied with hypertension remains unclear and is worth exploring.AimsFor this reason, this study aims at investigating differentially expressed proteins in clinical AMH tissue, with special focus on the potential contribution of these differentially expressed proteins to AMH development, in order to have a better understanding of mechanisms how AMH leads to secondary hypertension to some extent.Methods and resultsTo this end, AMH specimens were successfully obtained and verified through computed tomography (CT) and haematoxylin-eosin (HE) staining. Proteomic analyses of AMH and control tissues revealed 782 kinds of differentially expressed proteins. Compared with the control tissue, there were 357 types of upregulated proteins and 425 types of downregulated proteins detected in AMH tissue. Of interest, these differentially expressed proteins were significantly enriched in 60 gene ontology terms (P < 0.05), including 28 biological process terms, 14 molecular function terms, and 18 cellular component terms. Pathway analysis further indicated that 306 proteins exert their functions in at least one Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Western blotting showed enhanced expression of phenylethanolamine N- methyltransferase (PNMT), myelin protein zero (MPZ), and Ras-related protein Rab-3C (RAB3C), and reduced expression of cluster of differentiation 36 (CD36) observed in AMH tissue in comparison with controls.ConclusionsClinical AMH specimens display a different proteomic profile compared to control tissue. Of note, PNMT, MPZ, RAB3C, and CD36 are found to differentially expressed and can be potential targets for AMH, providing a theoretical basis for mechanistic exploration of AMH along with hypertension.

The weedy rice (Oryza sativa f. spontanea) harbors large numbers of excellent traits and genetic diversities, which serves as a valuable germplasm resource and has been considered as a typical material for research about de-domestication. However, there are relatively few reference genomes on weedy rice that severely limit exploiting these genetic resources and revealing more details about de-domestication events. In this study, a high-quality genome (~376.4 Mb) of weedy rice A02 was assembled based on Nanopore ultra-long platform with a coverage depth of about 79.3× and 35,423 genes were predicted. Compared to Nipponbare genome, 5,574 structural variations (SVs) were found in A02. Based on super pan-genome graph, population SVs of 238 weedy rice and cultivated rice accessions were identified using public resequencing data. Furthermore, the de-domestication sites of weedy rice and domestication sites of wild rice were analyzed and compared based on SVs and single-nucleotide polymorphisms (SNPs). Interestingly, an average of 2,198 genes about de-domestication could only be found by FST analysis based on SVs (SV-FST) while not by FST analysis based on SNPs (SNP-FST) in divergent region. Additionally, there was a low overlap between domestication and de-domestication intervals, which demonstrated that two different mechanisms existed in these events. Our finding could facilitate pinpointing of the evolutionary events that had shaped the genomic architecture of wild, cultivated, and weedy rice, and provide a good foundation for cloning of the superior alleles for breeding.

Objective: Paeoniae Radix Rubra (PRR) is a commonly used traditional Chinese medicine with the effects of clearing away heat, cooling the blood, and relieving blood stasis. To 1) elucidate the metabolites and metabolic pathways of PRR and its 14 main constituents in mice and 2) reveal the possible origins of the known effective forms of PRR and their isomers, the metabolism of PRR in mice was systematically studied for the first time.Methods: PRR and its 14 constituents were administered to mice by gavage once a day for seven consecutive days, respectively. All urine and feces were collected during the 7 days of dosing, and blood was collected at 1 h after the last dose. Metabolites were detected and identified using high performance liquid chromatography with diode array detector and combined with electrospray ionization ion trap time-of-flight multistage mass spectrometry (HPLC-DAD-ESI-IT-TOF-MSn).Results: In total, 23, 16, 24, 17, 18, 30, 27, 17, 22, 17, 33, 3, 8, 24, and 31 metabolites of paeoniflorin, albiflorin, oxypaeoniflorin, benzoylpaeoniflorin, hydroxybenzoylpaeoniflorin, benzoyloxypaeoniflorin, galloylpaeoniflorin, lactiflorin, epicatechin gallate, catechin gallate, catechin, ellagic acid, 3,3′-di-O-methylellagic acid, methylgallate, and PRR were respectively identified in mice; after eliminating identical metabolites, a total of 195 metabolites remained, including 8, 11, 25, 17, 18, 30, 27, 17, 21, 17, 1, 2, 8, 20, and 20 newly identified metabolites, respectively. The metabolic reactions of PRR and its 14 main constituents in mice were primarily methylation, hydrogenation, hydrolysis, hydroxylation, glucuronidation, and sulfation.Conclusion: We elucidated the metabolites and metabolic pathways of PRR and its 14 constituents (e.g., paeoniflorin, catechin, ellagic acid, and gallic acid) in mice and revealed the possible origins of the 10 known effective forms of PRR and their isomers. The findings are of great significance to studying the mechanism of action and quality control of PRR.

As an independent research field, there is growing attention to university–business cooperation (UBC). However, few studies focus on the driving factors of UBC, which remains an open problem in this area. This study analyzes a broad mix of drivers underlying seven UBC activities, namely, curriculum development and design (CDD), student mobility (SD), lifelong learning (LLL), professional mobility (PM), research and development (R&D), commercialization (COM), and entrepreneurship (ENT), and discusses the internal mechanism and external environment of higher education institutions (HEIs) as the moderator variable affecting UBC activities and individual motivations. Specifically, based on the social cognition theory, the independent variables include motivations (money, career, research, education, and social), the internal mechanism (support mechanism, strategic mechanism, and management mechanism), and the external environment (policy environment, economic environment, and cultural environment) are designed. The aforementioned seven UBC activities are taken as dependent variables. This work takes university faculty as the research object. Through empirical analysis, it demonstrates that the combination of driving factors of different UBC activities has its particularity. Furthermore, the results showed that the internal mechanism and external environment of HEIs could positively moderate the relationship between individual motivations and UBC activities. In terms of theoretical contribution, this study reveals the combination of factors that drive university faculty to engage in UBC. On the other hand, it can provide a reference for policymakers and managers to better development of UBC.

Colorectal cancer (CRC) is a common tumor disease of the digestive system with high incidence and mortality. Cuproptosis has recently been found to be a new form of cell death. The clinical significance of cuproptosis-related genes (CRGs) in CRC is not clear. In this study, The Cancer Genome Atlas Colon and Rectal Cancer dataset was used to analyze the relationship between CRGs and clinical characteristics of CRC by differential expression analysis and Kaplan–Meier survival (K-M) analysis. Based on CRGs, prognosis model and risk score of CRC was constructed in COADREAD by multivariate Cox analysis. Receiver operating curves (ROC) analysis, K-M analysis and calibration analysis in GDC TCGA Colon Cancer dataset were applied to validating model. Subsequently, the relationship between risk score of CRC and immune microenvironment was analyzed by multiple immune score algorithms. Finally, we found that most CRGs were differentially expressed between tumors and normal tissues. Some CRGs were differentially expressed among different clinical characteristics. K-M analysis showed that the CRGs were related to overall survival (OS), disease-specific survival, and progression-free survival. Subsequently, DLAT and CDKN2A were identified as risk factors for OS in CRC by multivariate Cox analysis, and the risk score was established. K–M analysis showed that there was a significant difference in OS between the high-risk and low-risk groups, which were grouped by risk score median. ROC analysis showed that the risk score performs well in predicting the 1-year, 3-year and 5-year OS. Enrichment analysis showed that the differentially expressed genes between the high- and low-risk groups were enriched in immune-related signaling pathways. Further analysis showed that there were significant differences in the levels of immune cells and stromal cells between the high- and low-risk groups. The high-risk group had higher levels of immune cells and interstitial cells. At the same time, the high-risk group had a higher immune escape ability, and the predicted immune treatment response in the high-risk group was poor. In conclusion, CRGs can be used as prognostic factors in CRC and are closely related to the levels of immune cells and stromal cells in the tumor microenvironment.

BackgroundApplying 3D printed prostheses to repair diaphyseal defects of lower limbs has been clinically conducted in orthopedics. However, there is still no unified reference standard for which the prosthesis design and fixation mode are more conducive to appropriate biomechanical conduction.MethodsWe built five different types of prosthesis designs and fixation modes, from Mode I to Mode V. Finite element analysis (FEA) was used to study and compare the mechanical environments of overall bone-prosthesis structure, and the maximum stress concentration were recorded. Additionally, by comparing the maximum von Mises stress of bone, intramedullary (IM) nail, screw, and prosthesis with their intrinsic yield strength, the risk of fixation failure was further clarified.ResultsIn the modes in which the prosthesis was fixed by an interlocking IM nail (Mode I and Mode IV), the stress mainly concentrated at the distal bone-prosthesis interface and the middle-distal region of nail. When a prosthesis with integrally printed IM nail and lateral wings was implanted (Mode II), the stress mainly concentrated at the bone-prosthesis junctional region. For cases with partially lateral defects, the prosthesis with integrally printed wings mainly played a role in reconstructing the structural integrity of bone, but had a weak role in sharing the stress conduction (Mode V). The maximum von Mises stress of both the proximal and distal tibia appeared in Mode III, which were 18.5 and 47.1 MPa. The maximum peak stress shared by the prosthesis, screws and IM nails appeared in Mode II, III and I, which were 51.8, 87.2, and 101.8 MPa, respectively. These peak stresses were all lower than the yield strength of the materials themselves. Thus, the bending and breakage of both bone and implants were unlikely to happen.ConclusionFor the application of 3D printed prostheses to repair diaphyseal defects, different fixation modes will lead to the change of biomechanical environment. Interlocking IM nail fixation is beneficial to uniform stress conduction, and conducive to new bone regeneration in the view of biomechanical point. All five modes we established have reliable biomechanical safety.

The tumor microenvironment (TME) plays a crucial role in tumor progression and metastasis. However, the immune phenotypes of colorectal cancer (CRC) and the underlying immune escape mechanism have not been studied sufficiently. A total of 1802 and 619 CRC samples from the microarray and TCGA cohorts were enrolled, respectively. The ssGSEA algorithm and unsupervised clustering were used for TME cell infiltration speculation and immune phenotype recognition in the above cohorts. A total of 447 samples from Zhongshan Hospital were collected for validation. Immunohistochemistry was performed in this cohort to quantify TME cell infiltration. The single-cell RNA-seq (scRNA-seq) data of 252,940 cells from 60 CRC samples was analyzed for further mechanistic exploration. CRC samples can be classified into three distinct immune phenotypes. Subtype 1, the immune-active subtype, was characterized by high infiltration of activated adaptive immune cells. Subtype 2, the immune-desert subtype, featured high tumor purity and low infiltration of immune and stromal cells. Subtype 3, the stroma-rich subtype, had high infiltration of stromal cells. The stroma-rich subtype conferred a significantly worse prognosis. The three subtypes had different immune escape mechanisms. The immune-active subtype has the highest immune checkpoint expression level. In comparison, the immune-desert subtype had the lowest immunogenicity and defective antigen presentation. The stroma-rich subtype lacked activated immune cells. In conclusion, distinct immune phenotypes and immune escape mechanisms may provide inspiration and direction for further research on CRC immunotherapy.

ObjectiveFractures of the thoracolumbar spine are the most common fractures of the spinal column. This retrospective cohort study aimed to determine whether it is necessary to remove implants of patients aged over 65 years after the fixation of thoracolumbar and lumbar burst fractures without fusion.MethodsThis retrospective cohort study included 107 consecutive patients aged ≥65 years without neurological deficits, who underwent non-fusion short posterior segmental fixation for thoracolumbar or lumbar burst fractures. Outcome measures included the visual analog score (VAS), Oswestry Disability Index (ODI), residual symptoms, complications, and imaging parameters. Patients were divided into groups A (underwent implant removal) and B (implant retention) and were examined clinically at 1, 3, 6, and 12 months postoperatively and annually thereafter, with a final follow-up at 48.5 months.ResultsOverall, 96 patients with a mean age of 69.4 (range, 65–77) years were analyzed. At the latest follow-up, no significant differences were observed in functional outcomes and radiological parameters between both groups, except in the local motion range (LMR) (P = 0.006). Similarly, between preimplant removal and the latest follow-up in group A, significant differences were found only in LMR (P

Soil salinity poses a serious threat to the sustainable production of rice (Oryza sativa L.) throughout the world. Thus, the detection of loci and alleles responsible for salt tolerance is fundamental to accelerating the improvement of rice and producing the resilient varieties that will ensure future harvests. In this study, we collected a set of 191 mini-core rice populations from around the world, evaluated their salt tolerance based on plant growth and development phenotypes at the seedling stage, and divided a standard evaluation score (SES) of visual salt injury into five different grades. We used ∼3.82 million single nucleotide polymorphisms (SNPs) to identify 155 significant SNPs and 275 genes associated with salt sensitivity based on a genome-wide association study (GWAS) of SES. In particular, two candidate genes, ZFP179 and OsDSR2, were associated with salt tolerance, and OsHKT1;1 was co-detected in the entire GWAS of all the panels and indica. Additionally, we investigated the transcriptional changes in cultivars 93-11 and PA64s under normal and salinity stress conditions and found 517 co-upregulated and 223 co-downregulated genes. These differentially expressed genes (DEGs) were highly enriched in “response to chemical” and “stress” based on the gene ontology enrichment analysis. Notably, 30 candidate genes that were associated with the salt tolerance analysis were obtained by integrating GWAS and transcriptomic DEG analyses, including 13 cloned genes that had no reports of tolerance to salt and 17 candidate genes whose functions were unknown. To further explore these genes and their alleles, we performed haplotype analysis, genome-wide domestication detection, and transcriptome analysis to breed improved varieties. This data and the genetic resources provided will be valuable for the development of salt tolerant rice varieties.

ObjectiveDisplaced intra-articular tongue-type fractures are often treated with surgical interventions, and there is a lack of consensus regarding the surgical approach. This retrospective cohort study aimed to compare percutaneous cannulated screw (PCS) fixation and plating with a minimally invasive longitudinal approach (MILA) after closed reduction for the treatment of tongue-type calcaneal fractures.Materials and MethodsA total of 77 patients with intra-articular tongue-type calcaneal fractures between September 2015 and July 2019 were included in this study. They were randomly allocated into two groups: PCS fixation (n = 32) and MILA (n = 45). The outcome measures included demographic variables, operation time (OT), preoperative time (POT), hospital stay time (HST), blood loss, visual analog scale (VAS) scores, American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scores, postoperative complications, and imaging parameters. The patients were clinically examined at 1, 3, 6, and 12 months, with a final follow-up period of 27 months.ResultsNo significant differences were observed during the follow-up in calcaneal length, height, Gissane's and Böhler's angles, VAS scores, AOFAS hindfoot scores, or complication rates between the two groups. However, the postoperative VAS scores in the PCS group were significantly lower than those in the MILA group (p < 0.05). Furthermore, the OT, POT, and HST in the PCS group were significantly shorter than those in the MILA group (p < 0.05). Blood loss was lower in the PCS group than those in the other group (p = 0.044). However, postoperative calcaneal widening was significantly smaller in the MILA group than that in the PCS group (p < 0.001).ConclusionsAfter closed reduction for the treatment of tongue-type calcaneal fractures, PCS fixation was superior to MILA in terms of OT, POT, HST, blood loss, pain, and degree of comfort. Meanwhile, MILA has the advantage of restoring the calcaneal width. Under the same rehabilitation program, the two approaches showed similar abilities in maintaining the closed reduction.

China set the goal of expanding early childhood education (ECE) in 2018, by encouraging the development of public interest kindergartens (PIK) to provide high-quality, low-cost preschool services to the general public. This is in response to the challenges of accessibility, affordability, and accountability besetting China’s current ECE system. However, the transition toward PIK has been slow due to various complex problems, including the lackluster willingness of ECE providers to become PIK. To better understand the challenges leading to low participation, this study explores the external pressures affecting ECE providers and evaluates the external factors that influence their level of social responsibility. A stratified-random sampling questionnaire survey solicited responses from 832 ECE personnel representing 261 kindergartens from across China. Our findings suggest that institutional pressure has a positive effect on social responsibility and inclusive participation. We also found that institution visibility positively regulates the relationship between institutional pressure and social responsibility. At the same time, the level of environmental perception positively governs the relationship between social responsibility and participation willingness. Kindergartens should have certain social values, including assuming certain behaviors and participating in social activities in the spirit of social service and ensure multiple subjects’ synergetic governance.

ObjectiveTo compare the clinical outcomes between use of sliding fixation (three cannulated screws, TCS) and non-sliding fixation (four cannulated screws, FCS) in the treatment of femoral neck fractures.MethodsWe retrospectively analyzed 102 patients with fresh femoral neck fractures treated with TCS (60 cases) and FCS (42 cases) between January, 2018 and December, 2019. The demographic data, follow-up time, hospitalization time, operation time, blood loss, length of femoral neck shortening (LFNS), soft tissue irritation of the thigh (STIT), Harris hip score, and complications (such as internal fixation failure, non-union, and avascular necrosis of the femoral head) were also collected, recorded, and compared between the two groups.ResultsA total of 102 patients with an average age of 60.9 (range, 18–86) years were analyzed. The median follow-up time was 25 (22 to 32) months. The LFNS in the FCS group (median 1.2 mm) was significantly lower than that in the TCS group (median 2.8 mm) (P < 0.05). In the Garden classification, the number of displaced fractures in the TCS group was significantly lower than that in the FCS group (P < 0.05). The median hospitalization time, operation time, blood loss, reduction quality, internal fixation failure rate (IFFR), STIT, and Harris hip score were not statistically different between the two groups (P > 0.05). However, in the subgroup analysis of displaced fractures, the LFNS (median 1.2 mm), STIT (2/22, 13.6%), and Harris hip score (median 91.5) of the FCS group at the last follow-up were significantly better than the LFNS (median 5.7 mm), STIT (7/16, 43.8%), and Harris hip score (median 89) of the TCS group (P < 0.05). No complications such as incision infection, deep infection, pulmonary embolism, or femoral head necrosis were found in either group.ConclusionTCS and FCS are effective for treating femoral neck fractures. For non-displaced fractures, there was no significant difference in the clinical outcomes between the two groups. However, for displaced fractures, the LFNS of the FCS is significantly lower than that of the TCS, which may reduce the occurrence of STIT and improve the Harris hip score.

BackgroundIntertrochanteric fractures increased quickly in past decades owing to the increasing number of aging population. Recently, geriatric co-management was rapidly emerging as a favored clinical care model for older patients with hip fractures. The purpose of this study was to assess the efficacy of a multidisciplinary team (MDT) co-management program in elderly patients with intertrochanteric fractures.MethodsIn this retrospective study, patients were divided into MDT group and traditional orthopedic care (TOC) group according to the healthcare model applied. 249 patients were included in the TOC group from January 2014 to December 2016 and 241 patients were included in the MDT group from January 2017 to December 2019. Baseline data, peri-operative data, and postoperative complications were collected and analyzed using SPSS 21.0.ResultsNo significant differences were observed between the two groups in terms of patient baseline characteristics. Patients in the MDT group had significantly lower time from admission to surgery and length-of-stay (LOS) compared with those in the TOC group. Furthermore, the proportion of patients receiving surgery within 24 h (61.4 vs. 34.9%, p < 0.001) and 48 h (80.9 vs. 63.5%, p < 0.001) after admission to the ward was significantly higher in the MDT group compared with those in the TOC group. In addition, patients in the MDT group had significantly lower proportion of postoperative complications (25.3 vs. 44.2%, p < 0.001), deep vein thrombosis (7.9 vs. 12.9%, p = 0.049), pneumonia (3.8 vs. 8.0%, p = 0.045) and delirium (4.1 vs. 9.2%, p = 0.025) compared with those in the TOC group. However, no significant changes were found for in-hospital and 30-day mortality.ConclusionThe MDT co-management could significantly shorten the time from admission to surgery, LOS, and reduce the postoperative complications for elderly patients with intertrochanteric fractures. Further research was needed to evaluate the impact of this model on patient health outcomes.

BackgroundConstipation and dementia have similar epidemiological characteristics. Changes in intestinal flora and characteristics of the brain-gut axis play roles in the pathogeneses of the two diseases, suggesting that there may be a close connection between the two. Most of the studies on constipation in dementia patients have focused on the population with α-synucleinopathies [Parkinson’s disease dementia (PDD), dementia with Lewy bodies (DLB)]. Few studies have reported the prevalence of constipation in all-cause dementia and mild cognitive impairment (MCI) populations.ObjectiveTo assess the prevalence of constipation in patients with all-cause dementia and MCI subtypes and to explore the association between constipation with dementia and MCI subtypes.MethodsFrom May 2019 to December 2019, we conducted a population-based cross-sectional survey. A total of 11,743 participants aged 65 or older from nine cities in China were surveyed. Participants underwent a series of clinical examinations and neuropsychological measurements. Constipation, dementia, MCI and MCI subtype were diagnosed according to established criteria through standard diagnostic procedures.ResultsThe overall age- and sex-adjusted prevalence of constipation in individuals aged 65 years and older was 14.8% (95% CI, 14.6–15.0). The prevalence rates of constipation were19.2% (95% CI, 17.3–21.0), 19.1% (95% CI, 16.8–21.5), 14.4% (95% CI, 12.8–15.9), and 13.8% (95% CI, 13.0–14.6) in the dementia, non-amnestic (na)-MCI, amnestic (a)-MCI and normal cognition populations, respectively. Multivariate logistic regression analysis showed that higher prevalence of constipation was associated with dementia (p = 0.0.032, OR = 1.18, 95% CI: 1.02–1.38) and na-MCI (p = 0.003, OR = 1.30, 95% CI: 1.09–1.54).ConclusionThe present study found a high prevalence of constipation in elderly individuals in China, and higher in patients with dementia and na-MCI.

AimWe aimed to examine the relationship between the Triglyceride–glucose (TyG) index and the incidence of type 2 diabetes in people with different phenotypes of obesity.MethodsFrom May 1, 1994 to December 31, 2016, 15,464 participants were enrolled in the medical examination program at the Murakami Memorial Hospital to determine the relationship between the TyG index and the incidence of type 2 diabetes in people with different phenotypes of obesity after 5.38 years of follow-up.ResultsBesides triglycerides, HbA1c%, and FPG, the incidence of type 2 diabetes was found to be significantly associated with the TyG index (p

BackgroundAll agents engaging sphongosine-1-phospate receptors (S1PRs) will have some cardiovascular effect. This study aimed to elucidate the risk of cardiovascular adverse events (AEs) in patients with multiple sclerosis (MS) treated with S1PR modulators (S1PRMs).MethodsWe systematically searched the PubMed, EMBASE, and Cochrane Library databases for randomised controlled trials (RCTs) published through January 5, 2021. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using the random-effects model. Sensitivity analyses and meta-regression were performed.ResultsSeventeen RCTs (12 for fingolimod; 3 for ozanimod; 2 for siponimod) involving 13,295 patients were included. Compared with the control treatment, S1PRMs significantly increased the risk of cardiovascular AEs (RR, 2.21; 95% CI, 1.58–3.10; I2, 75.6%). Notably, the high-risk cardiovascular AEs associated with S1PRMs were primarily bradyarrhythmia (RR, 2.92; 95% CI, 1.91–4.46; I2, 30.8%) and hypertension (RR, 2.00; 95% CI, 1.49–2.67; I2, 56.5%). Subgroup analysis results were consistent with the primary outcomes except that ozanimod was associated with a higher risk of hypertension only (RR, 1.76; 95% CI, 1.10–2.82; I2, 0.0%), while siponimod was associated with a higher risk of bradyarrhythmia only (RR, 2.75; 95% CI, 1.75–4.31; I2, 0.0%). No significant inter-subgroup differences were observed (Pinteraction > 0.05).ConclusionsS1PRM use increased the risk of cardiovascular AEs by 1.21 times in patients with MS, and increased risks for bradyarrhythmia and hypertension were at 2.92- and 2.00-fold, respectively. These findings can help clinicians assess the risk of cardiovascular AEs in patients treated with S1PRMs.Systematic Review RegistrationThe PROSPERO ID is CRD42020183215.

Nitrogen is essential for plant growth and yield, and it is, therefore, crucial to increase the nitrogen-use efficiency (NUE) of crop plants in fields. In this study, we measured four major low-nitrogen-induced growth response (LNGR) agronomic traits (i.e., plant height, tiller number, chlorophyll content, and leaf length) of the 225-rice-variety natural population from the Rice 3K Sequencing Project across normal nitrogen (NN) and low nitrogen (LN) environments. The LNGR phenotypic difference between NN and LN levels was used for gene analysis using a genome-wide association study (GWAS) combined with 111,205 single-nucleotide polymorphisms (SNPs) from the available sequenced data from the 3K project. We obtained a total of 56 significantly associated SNPs and 4 candidate genes for 4 LNGR traits. Some loci were located in the candidate regions, such as MYB61, OsOAT, and MOC2. To further study the role of candidate genes, we conducted haplotype analyses to identify the elite germplasms. Moreover, several other plausible candidate genes encoding LN-related or NUE proteins were worthy of mining. Our study provides novel insight into the genetic control of LNGR and further reveals some related novel haplotypes and potential genes with phenotypic variation in rice.

Background: Emerging knowledge has highlighted the role of matrix metalloproteinase (MMP)-13 in osteoarthritis (OA); however, the suitability of MMP-13 as a biomarker for OA remains unclear. Therefore, this study aimed to assess the potential value of MMP-13 as a biomarker for OA.Methods: The study enrolled 51 patients, of which 33 had advanced varus OA and 18 did not have OA. Immunohistochemistry and western blotting analyses were performed to measure MMP-13 activity in the cartilage and subchondral bone of patients with OA. Enzyme-linked immunosorbent assay was used to measure serum MMP-13 levels in patients with or without OA. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to assess the association between serum MMP-13 levels and clinical symptoms. Furthermore, the association between serum MMP-13 levels and radiological severity of OA was evaluated using the Kellgren–Lawrence (KL) grading system. Finally, we built the proportional odds logistic regression models to evaluate serum MMP-13 levels as a potential predictor for OA.Results: MMP-13 levels were significantly higher in the severe-worn cartilage of the medial tibial plateau than in the relatively intact portion of the lateral cartilage (p < 0.05). This was contrary to the findings for MMP-13 differential expression in the subchondral bone in knee OA (p < 0.05). Patients with OA had significantly higher serum MMP-13 levels compared with patients without OA. Additionally, remarkable associations among serum MMP-13 levels, WOMAC scores, and KL grading scores were found in the end-stage OA. Furthermore, the subsequent analysis suggested that serum MMP-13 level was a significant predictor for OA.Conclusion: MMP-13 is valuable for diagnosing, measuring disease severity, and predicting OA in the advanced period of the disease, suggesting that it has potential possibility as a biomarker for OA. However, the underlying mechanisms and clinical application of MMP-13 as a biomarker for OA require to be further investigated.

Background and Aims: There is a controversy regarding whether fingolimod is associated with an increased risk of infection in patients with multiple sclerosis (MS). We performed a systematic review and meta-analysis of data from randomized controlled trials (RCTs) to determine the risk of infection in these patients.Methods: We systematically searched PubMed, EMBASE, the Cochrane Library, and clinicaltrials.gov from inception to April 8, 2020, to identify RCTs that reported the occurrence of infection in patients with MS treated with fingolimod. Relative risks (RRs) and 95% confidence intervals (95% CIs) were calculated using the random-effects model.Results: Twelve RCTs including 8,448 patients were eligible. Compared with the control (placebo and other active treatments), fingolimod significantly increased the risk of infection (RR, 1.16; 95% CI, 1.07–1.27; I2, 81%), regardless of whether the infection was a general infection (RR, 1.14; 95% CI, 1.05–1.25; I2, 78%), or a serious infection (RR, 1.49; 95% CI, 1.06–2.10; I2, 0%). Analyses of subgroups found that fingolimod significantly increased the risk of lower respiratory infection (RR, 1.48; 95% CI, 1.19–1.85; I2, 0%) and herpes virus infection (RR, 1.34; 95% CI, 1.01–1.78; I2, 9%). There appears to be no dose-dependent increase in the risk of infection associated with fingolimod (0.5 mg: RR, 1.15; 95% CI, 1.07–1.25; I2, 91%; 1.25 mg: RR, 1.11; 95% CI, 0.97–1.28; I2, 81%; Pinteraction = 0.66).Conclusions: Compared with a placebo and other active treatments, fingolimod was associated with a 16% increase in the risk of infection, especially lower respiratory infection and herpes virus infection. The risk of infection associated with fingolimod might not be dose related.

The influence of ENSO events on winter precipitation anomalies in the Philippines has been well known since decades, but whether this effect is different between months needs further exploration. In this study, the monthly variations of precipitation over the Philippines in winter during the mature phases of ENSO events are investigated with datasets of reanalysis and observations from 1979 to 2019. Results indicate that only the eastern Pacific (EP) El Niño shows different influences on the Philippines winter precipitation among different months. In December during mature EP El Niño events, precipitation deficiency is not significant over the whole Philippines, whereas in January and February, precipitation decreases significantly over the southern Philippines as well as the areas to the southeast of the Philippines. Besides, the correlation between consecutive dry days over the southeast Philippines and ENSO is significantly positive in January and February but not in December. The eastward propagation of EP El Niño–related anomalous anticyclone over the western North Pacific (WNPAC) from December to February is proved responsible for the changed relationship between EP El Niño and precipitation. In December, the center of the WNPAC is located to the southeast of the Indo-China Peninsula, inducing weak lower-level wind anomalies and, consequently, weak vertical movement and water vapor transport anomalies over the Philippines, which exerts limited influence on the local precipitation. In January and February, by contrast, the center of WNPAC is located to the southeast of the Philippines, and therefore the southern Philippines is occupied by anticyclonic moisture transports and downward vertical motions, favoring less precipitations and larger than normal consecutive dry days over there.

Colorectal cancer is a major cause of death worldwide, and the identification of new diagnostic and prognostic biomarkers is crucial to develop new strategies to avoid colorectal cancer-related deaths. Small nuclear ribonucleoprotein polypeptide N (SNRPN) is an imprinted gene that plays an important role in various neurodevelopmental disabilities. In this study, SNRPN was highly expressed in colorectal cancer tissues and involved in the progression of this disease. Immunohistochemistry analysis of 1,310 colorectal cancer tissue samples showed that SNRPN highly expressed in cancer tissues than in adjacent tissues and was mainly localized in the nucleus. Clinical pathological factor analysis demonstrated that higher expression of SNRPN was significantly associated with larger tumor size, location of the tumor on the left-sided colon, neural invasion, and distant metastasis. Univariate and multivariate analyses showed that SNRPN expression was an independent risk factor for survival, with high expression levels indicating worse overall survival. Both in vitro and in vivo experiments confirmed that high expression of SNRPN was associated with tumor proliferation, cell cycle, and metastasis. Knocking down SNRPN blocked the cell cycle at the G2/M phase transition and promoted tumor cell apoptosis, inhibiting the progression of colorectal cancer. To explore the up-steam of SNRPN, we found by luciferase reporter assay and chromosomal immunoprecipitation assay that E2F8 was a transcriptional regulator up-steam of SNRPN in colorectal cancer. Systematic studies of SNRPN will help us discover new regulatory molecules and provide a theoretical basis for finding new molecular targets for this disease.

Background: Breast cancer is a very common cancer with significant premature mortality in women. In this study, we show that HKDC1 expression in breast cancer cells is increased significantly. We aim to investigate the detailed mechanism for the regulation of HKDC1 expression and its potential contribution to tumorigenesis.Methods: Gene expression was evaluated by real time PCR, western blotting, and immunohistochemistry. The mechanism for PGC1β/SREBP1-mediated HKDC1 expression was investigated using luciferase reporter assay, chromatin immunoprecipitation, and siRNA techniques. In addition, HKDC1 was overexpressed or knocked down by lentivirus to evaluate the potential effect on in vitro cell proliferation, glucose uptake, mitochondrial function, apoptosis, and reactive oxygen species (ROS) formation. Furthermore, an in vivo xenograft tumor development study was employed to investigate the effect of HKDC1 on tumor growth and mouse survival.Results: HKDC1 is highly expressed in both breast cancer cells and clinical tumor tissues. HKDC1 expression is upregulated and co-activated by PGC1β through SREBP1 binding motif on the HKDC1 promoter. HKDC1 is located on the mitochondrial membrane and regulates the permeability transition pore opening by binding with VDAC1, subsequently modulating glucose uptake and cell proliferation. Overexpression of HKDC1 increases while knockdown of HKDC1 decreases in vitro breast cancer cell proliferation and in vivo tumor growth, metastasis, and mouse survival.Conclusions: PGC1β regulates breast cancer tumor growth and metastasis by SREBP1-mediated HKDC1 expression. This provides a novel therapeutic strategy through targeting the PGC1β/HKDC1 signaling pathway for breast cancer treatment.

Phosphorus (P) deficiency is a predominant constraint on plant growth in acidified soils, largely due to the sequestration of P by toxic aluminum (Al) compounds. Indigenous phosphorus-solubilizing bacteria (PSBs) capable of mobilizing Al-P in these soils hold significant promise. A novel Al-P-solubilizing strain, Al-P Nguyenibacter sp. L1, was isolated from the rhizosphere soil of healthy Lespedeza bicolor plants indigenous to acidic terrains. However, our understanding of the genomic landscape of bacterial species within the genus Nguyenibacter remains in its infancy. To further explore its biotechnological potentialities, we sequenced the complete genome of this strain, employing an amalgamation of Oxford Nanopore ONT and Illumina sequencing platforms. The resultant genomic sequence of Nguyenibacter sp. L1 manifests as a singular, circular chromosome encompassing 4,294,433 nucleotides and displaying a GC content of 66.73%. The genome was found to host 3,820 protein-coding sequences, 12 rRNAs, and 55 tRNAs. Intriguingly, annotations derived from the eggNOG and KEGG databases indicate the presence of genes affiliated with phosphorus solubilization and nitrogen fixation, including iscU, glnA, and gltB/D associated with nitrogen fixation, and pqqBC associated with inorganic phosphate dissolution. Several bioactive secondary metabolite genes in the genome, including pqqCDE, phytoene synthase and squalene synthase predicted by antiSMASH. Moreover, we uncovered a complete metabolic pathway for ammonia, suggesting an ammonia-affinity property inherent to Nguyenibacter sp. L1. This study verifies the nitrogen-fixing and phosphate-dissolving abilities of Nguyenibacter sp. L1 at the molecular level through genetic screening and analysis. The insights gleaned from this study offer strategic guidance for future strain enhancement and establish a strong foundation for the potential incorporation of this bacterium into agricultural practices. [ABSTRACT FROM AUTHOR]

Aromatic Chinese herbs have been used to prevent plagues since ancient times. Traditional Chinese medicine has unique advantages in the prevention and treatment of epidemic diseases. According to the traditional Chinese medicine treatment plan in the National COVID-19 Diagnosis and Treatment Plan (Trial Seventh Edition) of the National Health Commission, Chinese patent medicines or prescriptions rich in aromatic Chinese herbs are selected for prevention and treatment during the period of medical observation, clinical treatment, and recovery of confirmed COVID-19 patients. Some local health committees or traditional Chinese medicine administrations recommend a variety of other ways of using traditional aromatic Chinese herbs to prevent and cure COVID-19. These involve external fumigation, use of moxibustion, and wearing of sachet. The efficacy of aromatic Chinese herbs plays a decisive role in the prevention and treatment of COVID-19. The unique properties, chemical composition, and mechanism of action of aromatic Chinese herbs are worthy of extensive and in-depth experimental and clinical research. The findings are expected to provide a reference for follow-up treatment of novel coronavirus and the development of corresponding drugs. In 2003, Dayuan-Yin produced excellent results in the treatment of the SARS virus. Individually, 112 confirmed cases were administered this drug between January and April 2003, and more than 93.7% of the patients showed noticeable mitigation of the symptoms, as well as recovery. Dayuan-Yin also was selected as one of the nationally recommended prescriptions for the COVID-19. Based on the national recommendation of Dayuan-Yin prescription, this review discusses the role of volatile components in the prevention and treatment of COVID-19, and speculates the possible mechanism of action, so as to provide a basis for the prevention and treatment of COVID-19.