Search

Background: Apoptosis is associated with the pathogenesis of Mycobacterium tuberculosis infection. This study aims to identify apoptosis-related genes as biomarkers for differentiating active tuberculosis (ATB) from latent tuberculosis infection (LTBI). Methods: The tuberculosis (TB) datasets (GSE19491, GSE62525, and GSE28623) were downloaded from the Gene Expression Omnibus (GEO) database. The diagnostic biomarkers differentiating ATB from LTBI were identified by combining the data of protein-protein interaction network, differentially expressed gene, Weighted Gene Co-Expression Network Analysis (WGCNA), and receiver operating characteristic (ROC) analyses. Machine learning algorithms were employed to validate the diagnostic ability of the biomarkers. Enrichment analysis for biomarkers was established, and potential drugs were predicted. The association between biomarkers and N6-methyladenosine (m6A) or 5-methylated cytosine (m5C) regulators was evaluated. Results: Six biomarkers including CASP1, TNFSF10, CASP4, CASP5, IFI16, and ATF3 were obtained for differentiating ATB from LTBI. They showed strong diagnostic performances, with area under ROC (AUC) values > 0.7. Enrichment analysis demonstrated that the biomarkers were involved in immune and inflammation responses. Furthermore, 24 drugs, including progesterone and emricasan, were predicted. The correlation analysis revealed that biomarkers were positively correlated with most m6A or m5C regulators. Conclusion: The six ARGs can serve as effective biomarkers differentiating ATB from LTBI and provide insight into the pathogenesis of Mycobacterium tuberculosis infection. [ABSTRACT FROM AUTHOR]

Background: The impact of the methylenetetrahydrofolate reductase (MTHFR) C677T mutation on the relationship between plasma homocysteine (Hcy) levels and stroke has been extensively studied and documented in previous study. However, it remains unclear whether the MTHFR C677T mutation can affect the response to Hcy lowering treatment in stroke patients with hyperhomocysteinemia (HHcy). Understanding the impact of genetic factors on treatment response can help optimize personalized treatment strategies for stroke patients with HHcy. We aimed to investigate the potential association between the MTHFR C677T gene polymorphisms and the effectiveness of Hcy lowering treatment using vitamin therapy in stroke patients with HHcy. Methods: The MTHFR C677T genotype polymorphisms were identified using polymerase chain reaction-restriction fragment length polymorphism, and the distribution of three genotypes in the MTHFR C677T gene locus was compared. The treatment effects of Hcy lowering agents were compared among patients with different genotypes. Results: Among the 320 stroke patients enrolled in the study, 258 (80.6%) were diagnosed with HHcy. Of these, 162 patients (Effective Group) responded well to the clinical Hcy lowering treatment, while 96 patients (Invalid Group) failed to achieve sufficient response even after taking combination supplements of folic acid, Vitamin B6, and methylcobalamin for one month. Significant differences were observed in terms of age (p < 0.001), hypertension (p = 0.034), dyslipidemia (p = 0.022), hyperuricemia (p = 0.013) and genotype distribution of MTHFR C677T gene polymorphism (p < 0.001) between the Invalid group and the Effective group. The multivariate regression analysis revealed that the T allele (odd rations [OR], 1.327; 95% confidence interval [CI], 1.114– 1.580; p = 0.0015) was independently associated with an insufficient Hcy lowering treatment effect. Additionally, the TT genotype was independently associated with insufficient response in both the codominant model (OR, 1.645; 95% CI, 1.093–2.476; p = 0.017) and the recessive model (TT versus CC + CT; OR, 1.529; 95% CI, 1.145–2.042; p = 0.004). However, no relationship was observed between CT + TT genotypes and poor treatment effect in the dominate model. Conclusions: Our findings suggested that the TT genotype and T allele of MTHFR C677T polymorphism were independently associated with an insufficient Hcy lowering treatment effect in stroke patients with HHcy. [ABSTRACT FROM AUTHOR]

Introduction: Traumatic brain injury (TBI) seriously affects the quality of human health and the prognosis of the patient, but the epidemiological characteristics of TBI can vary among populations. Numerous changes have occurred in the epidemiological characteristics of individuals with TBI in the fast-paced city of Shenzhen, China. However, little is known about these characteristics. This study aimed to investigate the changes in TBI epidemiology, help clinicians improve medical treatment. Methods: In this retrospective cross-sectional analysis, we collected the data of 4,229 patients with TBI admitted to 20 hospitals in Shenzhen in 2017. We collected data on age, gender, cause and severity of the injury, eventual diagnosis, time from injury to admission in a neurosurgery department, and patient outcomes. Two neurosurgeons simultaneously collected the data. We compared these results with a similar study conducted in Shenzhen during the period from 1994 to 2003 to clarify and explain the changes in the epidemiological characteristics of TBI. Results: The majority of respondents were men [2,830 (66.9%)]. The mean age was 32.5  ±  21.4  years. The youngest patient was less than 1  year old, and the oldest patient was 101  years old. A total of 3,947 (93.3%) patients had a favorable outcome, 219 (5.2%) had an unfavorable outcome, and 63 (1.5%) died. The predominant external cause was falls (1,779 [42.1%]); this was the most common cause of TBI in children and older adults. Riders of electric bicycles (423 [29.0%]) were the most vulnerable to traffic accident-related injuries. Time greater than 50  h from injury to admission to a neurosurgical department had a significant effect on prognosis (p  <  0.001). Conclusion: The epidemiological characteristics of TBI have changed significantly over the past 20  years. Falls, rather than traffic accidents, were the most common cause of TBI. Further research is needed to devise solutions to decrease the incidence of falls and improve the outcomes of TBI. [ABSTRACT FROM AUTHOR]

Abstract Aims Emergency department (ED) providers play an important role in the management of patients with acute heart failure (AHF). We present findings from a pilot study of an electronic decision support that includes personalized risk estimates using the STRIDE‐HF risk tool and tailored recommendations for initiating guideline directed medical therapy (GDMT) among appropriate patients. Methods Among ED patients treated for AHF who were discharged from the ED or the ED‐based observation unit in two EDs from 1 January 2023 to 31 July 2023, we assess prescriptions to the four classes of GDMT at two intervals: (1) ED arrival and (2) ED discharge. Specifically, we report active prescriptions for beta‐blockers (BBs), renin–angiotensin receptor system inhibitors (RASis), sodium‐glucose transport protein 2 inhibitors (SGLT2is) and mineralocorticoid receptor antagonists (MRA) among patients with reduced ejection fraction (HFrEF) and mildly reduced (HFmrEF). Second, we describe rates of 30‐day serious adverse events (SAE) (death, cardiopulmonary resuscitation, balloon‐pump insertion, intubation, new dialysis, myocardial infarction or coronary revascularization) among patients predicted to be very low risk by STRIDE‐HF and discharged home. Results Among 234 discharged patients, 55% were female and 76% were non‐White. We found 51 (21.8%), 21 (9.0%) and 126 (53.8%) had HFrEF, HFmEF and HFpEF, respectively, while 36 (15.4%) were missing EF, and 51 (22%) were very low risk, 82 (35%) were low risk, 60 (26%) were medium risk and 41 (18%) were high risk. Among HFrEF patients, 68.6%, 66.7%, 25.5% and 19.6% were on a RASi, BB, SGLT2i and MRA, respectively, at ED arrival, while 42.9%, 66.7%, 14.3% and 4.8% of HFmrEF patients were on a RASi, BB, SGLT2i and MRA, respectively. Among patients with HFpEF, only 6 (4.8%) were on an SGLT2i at ED arrival. The most prescribed new medication at ED discharge was an SGLT2i, with a nearly 10% increase in the proportion of patients with an active prescription for SGLT2i at ED discharge among HFrEF and HFmEF patients. We observed no 30‐day SAE among the 51 patients predicted to be very low risk and discharged home. Conclusions Ongoing treatment with GDMT at ED arrival was sub‐optimal. Initiation among appropriate patients at discharge may be feasible and safe.

Abstract The emergence and rapid spread of multidrug-resistant bacterial strains is a growing concern of public health. Inspired by the natural bactericidal surfaces of lotus leaves and shark skin, increasing attention has been focused on the use of mechano-bactericidal methods to create surfaces with antibacterial and/or bactericidal effects. There have been several studies exploring the bactericidal effect of nanostructured surfaces under various combinations of parameters. However, the correlation and synergies between these factors still need to be clarified. Recently machine learning (ML), which enables prediction or decision-making based on data, has been used in the field of biomaterials with promising results. In this study, we explored ML in nanotechnology to investigate the antimicrobial potential of nanostructured surfaces. A dataset of nanostructured surfaces and their antimicrobial properties was built by extracting the published literature. Based on the literature review and the distribution of our dataset, 70% bactericidal efficiency was selected as a practical benchmark for our classification model that balances stringent bactericidal performance with achievable targets in diverse conditions. Subsequently, we developed an ML classification model, which demonstrated an 81% accuracy in its predictive capability. A regression model was further developed to predict the value of bactericidal efficiency for nanostructured surfaces. Feature importance analysis of the ML models suggested that nanotopographical features have a greater influence on bactericidal properties than material properties, thus providing insight into the principles of the mechano-bactericidal effect of nanostructured surfaces. Overall, this ML model tool could help researchers to effectively select and design the parameters of the surface structure prior to experimentation, thereby improving the timeliness and reducing the number of experiments and the associated costs. Graphical Abstract

Technique: Hepatocellular adenoma (HCA) is a benign monoclonal tumour that originates from mature hepatocytes.Liver resection is recommended in case of overt malignant transformation to hepatocellular carcinoma.However, hepatobiliary surgeries are technically challenging in patients with giant HCA (GHCA) owing to the risk of catastrophic intraoperative bleeding and difficulty with its control during laparoscopic treatment. We present a technical note on the utilization of the hepatic vein as anatomical landmarks for laparoscopic removal of giant hepatic glands, without intraoperative ultrasonography and with the aid of an augmented reality navigation system during surgery. Results: This video shows aA 37-year-old man was recommended treatment for a progressively increasing HCA (from 3 to 10 cm in a year) involving the right hepatic vein (RHV), inferior vena cava (IVC) and middle hepatic vein (MHV), resulting in the invisibility of the above intrahepatic anatomic markers in CT. Laparoscopic hepatectomy was performed using the hepatic vein as anatomic markers in a treatment centre specialising in minimally invasive surgeries. The procedure involved fully mobilising the right liver, transecting the parenchyma along the demarcation line in the caudal-to-cranial direction, exposing the involved caudal MHV, isolating and transecting the involved RHV and preserving the integrity of the involved IVC. Conclusions: Laparoscopic hepatectomy for intractable GHCA using the involved intrahepatic anatomic markers is feasible and effective. It reduces pre-operative haemorrhage and open conversion rates while maximising postoperative hepatic function.

Abstract Most angiosperm plants recognise the 22-residue flagellin (flg22) epitope in bacterial flagellin via homologs of cell surface receptor FLS2 (flagellin sensitive-2) and mount pattern-triggered immune responses. However, flg22 is buried within the flagellin protein indicating that proteases might be required for flg22 release. Here, we demonstrate the extracellular subtilase SBT5.2 not only releases flg22, but also inactivates the immunogenicity of flagellin and flg22 by cleaving within the flg22 epitope, consistent with previous reports that flg22 is unstable in the apoplast. The prolonged lifetime of flg22 in sbt5.2 mutant plants results in increased bacterial immunity in priming assays, indicating that SBT5.2 counterbalances flagellin immunogenicity to provide spatial-temporal control and restrict costly immune responses and that bacteria take advantage of the host proteolytic machinery to avoid detection by flagellin having a protease-sensitive flg22 epitope.

Abstract Background Thoracic epidural anesthesia (TEA) is associated with a knowledge gap regarding its mechanisms in lung protection and reduction of postoperative pulmonary complications (PPCs). Driving pressure (ΔP), an alternative indicator of alveolar strain, is closely linked to reduced PPCs with lower ΔP values. We aim to investigate whether TEA contributes to lung protection by lowering ΔP during mechanical ventilation. Methods In this prospective, randomized, patient and evaluator-blinded parallel study, adult patients scheduled for elective major upper abdominal surgery were assigned to either the TEA group with combined thoracic epidural anesthesia and general anesthesia (TEA-GA) (n = 30) or the control group with only general anesthesia (GA) (n = 30). Measurements The primary outcome was the minimum ΔP determined based on positive end-expiratory pressure (PEEP) after intubation. Secondary outcomes included the incidence of PPCs within seven days, the minimum ΔP at various time points, blood gas analysis, intensive care unit (ICU) admission rates, length of hospital stay, and 30-day mortality rate. Results The TEA group had a significantly lower minimum ΔP titrated based on PEEP compared to the control group (11.23 ± 2.19 cmH2O vs. 12.67 ± 2.70 cmH2O; P = 0.028). Multivariate linear regression analysis showed that intraoperative TEA application (compared with its absence; unstandardized beta coefficient (B) = -1.289; P = 0.008) significantly correlated with ΔP. The incidence of PPCs did not differ significantly between the two groups (8 of 30 [26.7%] vs. 12 of 30 [40%]; P = 0.273), but the incidence of atelectasis in the TEA group was significantly lower than in the control group (5 of 30 [16.7%] vs. 12 of 30 [40.7%]; P = 0.012). Multivariate logistic regression analysis indicated that ΔP was the only variable significantly associated with PPCs (Adjusted Odds Ratio [OR] = 2.190; 95% Confidence Interval [CI]: 1.300 to 3.689; P = 0.003). Conclusion Compared to GA, TEA-GA can reduce intraoperative ΔP in patients undergoing major upper abdominal surgery, especially those undergoing laparoscopic surgery. However, compared to GA combined with ΔP-guided ventilation, TEA-GA combined with ΔP-guided ventilation does not reduce the risk of PPCs. There was no significant difference in the total use of various vasoactive drugs between the two groups. Trial registration This study was registered in the Chinese Clinical Trial Registry (registration number ChiCTR2300068778 date of registration February 28, 2023).

Abstract The initial fine-tuning processes are crucial for successful bone regeneration, as they guide skeletal stem cells through progenitor differentiation toward osteo- or chondrogenic fate. While fate determination processes are well-documented, the mechanisms preceding progenitor commitment remain poorly understood. Here, we identified a transcription factor, Zfp260, as pivotal for stem cell maturation into progenitors and directing osteogenic differentiation. Zfp260 is markedly up-regulated as cells transition from stem to progenitor stages; its dysfunction causes lineage arrest at the progenitor stage, impairing bone repair. Zfp260 is required for maintaining chromatin accessibility and regulates Runx2 expression by forming super-enhancer complexes. Furthermore, the PKCα kinase phosphorylates Zfp260 at residues Y173, S182, and S197, which are essential for its functional activity. Mutations at these residues significantly impair its functionality. These findings position Zfp260 as a vital factor bridging stem cell activation with progenitor cell fate determination, unveiling a element fundamental to successful bone regeneration.

Abstract Zero-shot relation extraction (ZSRE) is essential for improving the understanding of natural language relations and enhancing the accuracy and efficiency of natural language processing methods in practical applications. However, the existing ZSRE models ignore the importance of semantic information fusion and possess limitations when used for zero-shot relation extraction tasks. Thus, this paper proposes a dual contrastive learning framework and a cross-attention network module for ZSRE. First, our model designs a dual contrastive learning framework to compare the input sentences and relation descriptions from different perspectives; this process aims to achieve better separation between different relation categories in the representation space. Moreover, the cross-attention network of our model is introduced from the computer vision field to enhance the attention paid by the input instance to the relevant information of the relation description. The experimental results obtained on the Wiki-ZSL and FewRel datasets fully demonstrate the effectiveness of our approach.

The newt genus Tylototriton is widely distributed in east, southeast, and south Asia. Previous studies have shown that basic surveys of this genus are far from comprehensive, and unknown species still exist within the group. In this study, we described a new species of this genus, Tylototriton gaowangjienensis sp. nov., from Gaowangjie National Nature Reserve in Hunan Province, China, based on evidence from molecular identification and morphological comparisons. Additionally, we conducted phylogenetic analysis of the genus to elucidate the taxonomic status of the new species. Based on combined mitochondrial 16S rRNA and ND2 gene sequences, the phylogenetic tree supported the new species as a member of the T. wenxianensis species subclade in the subgenus Yaotriton. It can be distinguished from its congeners by the combination of the following characteristics: (1) medium-sized body; (2) finger tips extending beyond the snout while forelimbs stretched forward; (3) tips of forelimbs and hindlimbs reaching and overlapping when folded towards the body; (4) snout edge round; (5) absence of small papillae in the male cloacal fissure; (6) dorsal ridges narrow, with width smaller than the eye diameter; (7) head length (HDL) greater than head width (HDW) (HDL/HDW = 1.04~1.22); (8) orange markings absence on the parotoid; (9) nodule-like warts on body sides continuous; (10) vomerine teeth not connected at the tip, extending to the occipital bone at the posterior end.

Abstract Through the energy transfer process, mild transformations can be achieved that are often difficult to realize under thermodynamic conditions. Herein, a visible-light-driven deoxygenative coupling of 1,2-dicarbonyl compounds for C–O, C–S, and C–N bonds construction is developed via triplet state 1,2-dicarbonyls, affording a wide range of α-functionalized ketones/esters under transition-metal and external photocatalyst free conditions. The usefulness of this method is demonstrated by gram-scale synthesis, late-stage functionalization of various carboxylic acid drugs, and the synthesis of natural products and drug molecules.