Advancements in inhibitors of crucial enzymes in the cysteine biosynthetic pathway: Serine acetyltransferase and O-acetylserine sulfhydrylase.

Infectious diseases have been jeopardized problem that threaten public health over a long period of time. The growing prevalence of drug-resistant pathogens and infectious cases have led to a decrease in the number of effective antibiotics, which highlights the urgent need for the development of new antibacterial agents. Serine acetyltransferase (SAT), also known as CysE in certain bacterial species, and O-acetylserine sulfhydrylase (OASS), also known as CysK in select bacteria, are indispensable enzymes within the cysteine biosynthesis pathway of various pathogenic microorganisms. These enzymes play a crucial role in the survival of these pathogens, making SAT and OASS promising targets for the development of novel anti-infective agents. In this comprehensive review, we present an introduction to the structure and function of SAT and OASS, along with an overview of existing inhibitors for SAT and OASS as potential antibacterial agents. Our primary focus is on elucidating the inhibitory activities, structure-activity relationships, and mechanisms of action of these inhibitors. Through this exploration, we aim to provide insights into promising strategies and prospects in the development of antibacterial agents that target these essential enzymes.

Predicting papillary thyroid microcarcinoma in American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) 3 nodules: radiomics analysis based on intratumoral and peritumoral ultrasound images.

Background: A subset of patients undergoing thyroid surgery for presumed benign thyroid disease presented with papillary thyroid microcarcinoma (PTMC). A non-invasive and precise method for early recognition of PTMC are urgently needed. The aim of this study was to construct and validate a nomogram that combines intratumoral and peritumoral radiomics features as well as clinical features for predicting PTMC in the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) 3 nodules using ultrasonography. Methods: A retrospective review was conducted on a cohort of 221 patients who presented with ACR TI-RADS 3 nodules. These patients were subsequently pathologically diagnosed with either PTMC or benign thyroid nodules. These patients were randomly divided into a training and test cohort with an 8:2 ratio for developing the clinical model, intratumor-region model, peritumor-region model and the combined-region model respectively. The radiomics features were extracted from ultrasound (US) images of each patient. We employed K-nearest neighbor (KNN) model as the base model for building the radiomics signature and clinical signature. Finally, a radiomics-clinical nomogram that combined intratumoral and peritumoral radiomics features as well as clinical features was developed. The prediction performance of each model was assessed by the area under the curve (AUC), sensitivity, specificity and calibration curve. Results: A total of 23 radiomics features were selected to develop radiomics models. The combined-region radiomics model showed favorable prediction efficiency in both the training dataset (AUC: 0.955) and the test dataset (AUC: 0.923). A radiomics-clinical nomogram was constructed and achieved excellent calibration and discrimination, which yielded an AUC value of 0.950, a sensitivity of 0.950 and a specificity of 0.920. Conclusions: This study proposed the nomogram that contributes to the accurate and intuitive identification of PTMC in ACR TI-RADS 3 nodules.

Cryogenic Photoelectron Spectroscopic and Theoretical Study of the Electronic and Geometric Structures of Undercoordinated Osmium Chloride Anions OsCln- (n = 3-5).

A series of anionic transition metal halides, OsCln- (n = 3-5), have been investigated using a newly developed, home-constructed, cryogenic anion cluster photoelectron spectroscopy. The target anionic species are generated through collision-induced dissociation in a two-stage ion funnel. The measured vertical detachment energies (VDEs) are 3.48, 4.54, and 4.81 eV for n = 3, 4, and 5, respectively. Density functional theory calculations at the B3LYP-D3(BJ)//aug-cc-pVTZ(-pp) level predict the lowest energy structures of the atomic form of OsCln- (n = 3-5) to be a quintet triangle, quartet square, and quintet square-based pyramid, respectively. The CCSD(T)-calculated VDEs and corresponding adiabatic detachment energies agree well with our experimental measurements. Analysis of the corresponding frontier molecular orbitals and charge density differences suggests that the d-orbitals of the transition metal Os play a primary role in the single-photon detachment processes, and the detached electrons originating from different molecular orbitals are distinguishable.

Performance of salivary glands ultrasonography, shear wave elastography and their combined use for the diagnosis of primary and secondary Sjögren's syndrome.

BACKGROUND: Sjögren's syndrome (SS) is a common rheumatic disease for which finding the right imaging tool remains a challenge. PURPOSE: This study aimed to evaluate the performance of salivary gland ultrasonography (SGUS), shear wave elastography (SWE) and their combined use for the diagnosis of primary and secondary SS (pSS and sSS). METHODS: This retrospective study included patients with dry symptoms who underwent routine examinations between May 2019 and December 2023. Patients were categorized into the pSS (n = 41), sSS (n = 26), and control (n = 27) groups based on the American College of Rheumatology/European League Against Rheumatism classification criteria (2016). A comparison of SGUS and shear wave velocity (SWV) results was conducted among the three groups. The diagnostic capabilities of different ultrasound methods for SS were evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC) for specificity. RESULTS: Compared to the control group, both the pSS (1.80 ± 1.03 vs. 0.67 ± 0.48, p < 0.001) and the sSS (1.85 ± 0.88 vs. 0.67 ± 0.48, p < 0.001) groups exhibited significantly elevated SGUS scores. However, there was no statistically significant difference between the pSS and sSS groups (p = 0.849). The SWV values in both the pSS and sSS groups were significantly higher than those in the control group (all p < 0.001). The AUC for diagnosing SS using only SGUS scores was 0.823 (95% confidence interval [CI]: 0.731-0.894). Combining SGUS scores and SWV values resulted in improved diagnostic accuracy (AUC: 0.883, 95% CI: 0.801-0.940). CONCLUSIONS: SGUS and SWE are pivotal in the diagnosis of Sjögren's syndrome, with their synergistic application poised to bolster diagnostic precision. This combined approach also furnishes substantial backing for the clinical assessment and management of Sjögren's syndrome.

Decoding connections in the European population: serum uric acid, sex hormone-binding globulin, total testosterone, estradiol, and female infertility - advanced bidirectional and mediative Mendelian randomization.

Background: Despite observational links between serum uric acid (SUA), sex hormone-related phenotypes, and female infertility, the causality behind these associations remains uncertain. Objective: This study utilizes Bidirectional Two-Sample and Mediation Mendelian Randomization to explore the causal relationships and mediation effects of sex hormone-binding globulin (SHBG), total testosterone (TT), and estradiol on these associations. Methods: We analyzed single-nucleotide polymorphisms (SNPs) associated with SUA and sex hormone levels using data from large-scale GWAS of European populations. Female infertility data were sourced from 6,481 cases and 75,450 controls in the FinnGen Consortium. We employed methods including Inverse Variance Weighted (IVW), Weighted Median, and MR-Egger regression to assess causality. Results: We found that elevated SUA levels causally increase the risk of female infertility (IVW OR: 1.13, P=0.047). Elevated SUA levels significantly decrease SHBG levels (ß=-0.261; P=2.177e-04), with SHBG mediating 27.93% of the effect of SUA on infertility (OR=0.854; 95%CI, 0.793-0.920; P=2.853e-05). Additionally, elevated TT levels, which were associated with decreased SUA levels (ß=-0.127), showed an indirect effect on infertility mediated by SUA (ß=-0.0187; 95% CI, -0.041 to -0.003; P=0.046). Conclusion: Our findings demonstrate causal links between high SUA and increased risk of female infertility mediated by hormonal factors such as SHBG and TT. These insights suggest new avenues for infertility treatment and highlight the need for further research into these mechanisms.

Cross-Combination Analyses of Random Forest Feature Selection and Decision Tree Model for Predicting Intraoperative Hypothermia in Total Joint Arthroplasty.

BACKGROUND: In total joint arthroplasty patients, intraoperative hypothermia (IOH) is associated with perioperative complications and an increased economic burden. Previous models have some limitations and mainly focus on regression modeling. Random forest (RF) algorithms and decision tree modeling are effective for eliminating irrelevant features and making predictions that aid in accelerating modeling and reducing application difficulty. METHODS: We conducted this prospective observational study using convenience sampling and collected data from 327 total joint arthroplasty patients in a tertiary hospital from March 4, 2023 to September 11, 2023. Of those, 229 patients were assigned to the training and 98 to the testing sets. The Chi-square, Mann-Whitney U, and t-tests were used for baseline analyses. The feature variables selection used the RF algorithms, and the decision tree model was trained on 299 examples and validated on 98. The sensitivity, specificity, recall, F1 score, and area under the curve (AUC) were used to test the model's performance. RESULTS: The RF algorithms identified the preheating time, the volume of flushing fluids, the intraoperative infusion volume, the anesthesia time, the surgical time, and the core temperature after intubation as risk factors for IOH. The decision tree was grown to five levels with nine terminal nodes. The overall incidence of IOH was 42.13%. The sensitivity, specificity, recall, F1 score, and AUC were 0.651, 0.907, 0.916, 0.761, and 0.810, respectively. The model indicated strong internal consistency and predictive ability. CONCLUSIONS: The preheating time, the volume of flushing fluids, the intraoperative infusion volume, the anesthesia time, the surgical time, and the core temperature after intubation could accurately predict IOH in total joint arthroplasty patients. By monitoring these factors, the clinical staff could achieve early detection and intervention of IOH in total joint arthroplasty patients.

[Retracted] lncRNA ST8SIA6­AS1 facilitates proliferation and invasion in liver cancer by regulating miR­142­3p.

[This retracts the article DOI: 10.3892/etm.2021.10783.].

Clinical and laboratory characteristics of salivary gland ultrasonography-positive patients with primary Sjögren's syndrome.

OBJECTIVE: This study aimed to investigate the clinical and laboratory characteristics of salivary gland ultrasonography (SGUS)-positive patients with primary Sjögren's syndrome (pSS) compared to SGUS-negative patients and to analyse the diagnostic value of SGUS and labial salivary gland biopsy (LSGB) grading in pSS. METHODS: A retrospective analysis of patients admitted to the Affiliated Hospital of Yangzhou University between May 2019 and November 2023 was conducted. According to the OMERACT scoring system, patients with pSS were divided into an SGUS-negative group (score <2) and an SGUS-positive group (score ≥2). The patient's age, gender, clinical symptoms, laboratory parameters and diagnostic examinations were compared and analysed, and Spearman correlation analysis was used to analyse the correlation between SGUS, LSGB and influencing factors. RESULTS: There was no significant difference in dry mouth, dry eyes, tooth loss, fever, joint pain, fatigue, interstitial lung disease or renal tubular acidosis between the two groups, although there were more patients with salivary gland enlargement in the SGUS-positive group (p < 0.05). In terms of high levels of immunoglobulin G (IgG), high levels of rheumatoid factor (RF), anti-nuclear antibody ≥1:320, anti-Sjögren's syndrome A-52KD and anti-Sjögren's syndrome B, the number of cases in the SGUS-positive group was greater than that in the SGUS-negative group (p < 0.05). LSGB samples were graded per the Chisholm-Mason system with significant differences between multiple groups. SGUS score negatively correlated with age and positively correlated with LSGB grade. CONCLUSION: This study showed that the SGUS score positively correlated with LSGB grade in pSS patients and negatively correlated with patient age. Thus, SGUS and LSGB are consistent in the diagnosis of pSS to reflect the degree of salivary gland involvement, and patients who are SGUS positive have high RF and IgG levels, a variety of autoantibodies positive and a tendency toward salivary gland enlargement.

Construction and validation of a prognostic and therapeutic cuproptosis- and immune-related gene signature in hepatocellular carcinoma.

Background: Abnormal accumulation of copper could induce cell death and tumor growth, and affect tumor immune escape by regulating programmed cell death ligand 1 (PD-L1) expression. This study aims to establish and verify a risk signature based on cuproptosis- and immune-related genes (CIRGs) for hepatocellular carcinoma (HCC) management. Methods: HCC RNA-seq and clinical data were obtained from open databases. Least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were utilized to screen CIRGs and develop a risk signature. The signature's value for clinical applications, functional enrichment, tumor mutation burden (TMB), and immune profile analyses were investigated systematically. Results: A risk signature was developed utilizing seven CIRGs, and it performed well in predicting the prognosis of HCC patients in both the training and external validation cohorts. The model's risk score was discovered to be related to important clinical features. Top 15 mutated genes in HCC were significantly different among different risk groups. High-risk patients showed higher TMB, and high TMB was closely identified with a poorer prognosis. Immune profile analyses showed that immune infiltration level was higher in low-risk patients than high-risk patients, and the level of immune checkpoint genes expression varied significantly between patients in two different risk groups. Low-risk patients responded well to immunotherapy treatment, whereas high-risk patients were more sensitive to sorafenib, doxorubicin, gemcitabine and AKT (also known as protein kinase B) inhibitors. Conclusions: The established risk signature based on CIRGs can not only well predict the prognosis of HCC patients but is also promising in evaluating TMB and treatment response to immunotherapy, targeted therapy and chemotherapy, which has the potential to assist in the clinical management of HCC.

Ultrasensitive Electrochemiluminescence Biosensing Platform Based on Polymer Dots with Aggregation-Induced Emission for Dual-Biotoxin Assay.

Multitarget assay has always been a hot topic in electrochemiluminescence (ECL) methods. Herein, a "on-off-on" ECL aptasensor was developed for the ultrasensitive and sequential detection of possible biological warfare agents, deoxynivalenol (DON) and abrin (ABR). As a luminophore, polymer dots (Pdots) with aggregation-induced emission exhibit high ECL efficiency in the aptasensor, i.e., the signal "on" state. The DON assays mainly depend on ECL quenching due to the efficient quenching effect between ferrocene-H2-ferrocene (Fc-H2-Fc) and Pdots, i.e., the signal "off" state. When the aptasensor is incubated with the oligonucleotide sequence S2 to replace Fc-H2-Fc, obvious ECL recovery occurs, i.e., the signal "on" state, which can be used to sequentially detect ABR. The limit of detection (LOD) for DON is 0.73 fg·mL-1 in the range of 5.0 to 50 ng·mL-1; and the LOD for ABR is ∼0.38 pg·mL-1 in the range of 1.25 pg·mL-1 to 1.25 µg·mL-1. The as-designed ECL aptasensor exhibits good stability and reproducibility, high specificity, and favorable practicality. Therefore, this work provides a new approach for assays of DON and ABR in food safety and can be used as a model to design an ultrasensitive ECL biosensor for multitarget detection.

Association between sleep duration and subjective memory complaints: A large-scale cross-sectional study based on NHANES.

Objective: When chatting, people often forget what they want to say, that is, they suffer from subjective memory complaints (SMCs). This research examines the Association between sleep duration and self-reported SMC in a sample representing the entire United States. Methods: We examined data from 5567 individuals (aged 20-80) who participated in the National Health and Nutrition Examination Survey (2015-2018) to evaluate the association between sleep duration and SMC. Odds ratios (ORs) and a restricted cubic spline (RCS) curve were calculated with multiple logistic regression, and subgroup analysis was performed. Results: Approximately 5.8 % (3 2 3) reported SMC, and most are older people (1 6 3). RCS analysis treating sleep duration as a continuous variable revealed a J-shaped curve association between sleep duration and SMC. Self-reported sleep duration was significantly linked to a 33 % elevated risk of SMC (OR, 1.33; 95 % confidence interval [CI], 1.23-1.43; P < 0.001). In the group analysis, individuals who slept more than 8 h per day had a greater association of experiencing SMC than those who slept for 6-8 h/day (OR, 1.75; 95 % CI, 1.36-2.23; P < 0.001). In the analysis of age groups, the stable association between sleep duration and SMC was observed only in the 60-80 age bracket (OR, 1.59; 95 % CI, 1.09-2.33; P < 0.001). Conclusions: We found that people with self-report sleep duration exceeding 8 h are more likely to experience SMC, especially older adults. Improving sleep health may be an effective strategy for preventing SMC and cognitive impairment.

Attribute Prototype-guided Iterative Scene Graph for Explainable Radiology Report Generation.

The potential of automated radiology report generation in alleviating the time-consuming tasks of radiologists is increasingly being recognized in medical practice. Existing report generation methods have evolved from using image-level features to the latest approach of utilizing anatomical regions, significantly enhancing interpretability. However, directly and simplistically using region features for report generation compromises the capability of relation reasoning and overlooks the common attributes potentially shared across regions. To address these limitations, we propose a novel region-based Attribute Prototype-guided Iterative Scene Graph generation framework (AP-ISG) for report generation, utilizing scene graph generation as an auxiliary task to further enhance interpretability and relational reasoning capability. The core components of AP-ISG are the Iterative Scene Graph Generation (ISGG) module and the Attribute Prototype-guided Learning (APL) module. Specifically, ISSG employs an autoregressive scheme for structural edge reasoning and a contextualization mechanism for relational reasoning. APL enhances intra-prototype matching and reduces inter-prototype semantic overlap in the visual space to fully model the potential attribute commonalities among regions. Extensive experiments on the MIMIC-CXR with Chest ImaGenome datasets demonstrate the superiority of AP-ISG across multiple metrics.

Insights into the antineoplastic activity and mechanisms of action of coumarin-coordinated 8-hydroxyquinoline ruthenium(II/III) compounds.

Ruthenium(II/III) coordination compounds have gained widespread attention as chemotherapy drugs, photosensitizers, and photodynamic therapy reagents. Herein, a family of 11 novel coumarin-coordinated 8-hydroxyquinoline ruthenium(II/III) compounds, i.e., [RuII2(µ2-Cl)2(QL1a)2(DMSO)4] (YNU-4a = Yulin Normal University-4a), [RuII2(µ2-Cl)2(QL1b)2(DMSO)4] (YNU-4b), [RuII2(µ2-Cl)2(QL1c)2(DMSO)4] (YNU-4c), [RuII2(µ2-Cl)2(QL1d)2(DMSO)4]⋅2CH3OH (YNU-4d), [RuII(QL1e)2(DMSO)2] (YNU-4e), [RuIII(QL1e)2(QL3a)] (YNU-4f), [RuIII(QL1e)2(QL3b)] (YNU-4g), [RuIII(QL1e)2(QL3c)] (YNU-4h), [RuIICl2(H-QL3a)2(DMSO)2] (YNU-4i), [RuIICl2(H-QL3b)2(DMSO)2] (YNU-4j), and [RuIICl2(H-QL3c)2(DMSO)2] (YNU-4k), featuring the coligands 5,7-diiodo-8-hydroxyquinoline (H-QL1a), 5,7-dichloro-8-quinolinol (H-QL1b), 5-chloro-7-iodo-8-hydroxyquinolin (H-QL1c), 5,7-dibromo-8-hydroxyquinoline (H-QL1d), and 5,7-dichloro-8-hydroxy-2-methylquinoline (H-QL1e) and the main ligands 6,7-dichloro-3-pyridin-2-yl-chromen-2-one (H-QL3a), 6-bromo-3-pyridin-2-yl-chromen-2-one (H-QL3b), and 6-chloro-3-pyridin-2-yl-chromen-2-one (H-QL3c), respectively. The structure of compounds YNU-4a-YNU-4k was fully confirmed by conducting various spectroscopic analyses. The anticancer activity of YNU-4a-YNU-4k was evaluated in cisplatin-resistant A549/DDP lung cancer cells (LC549) versus normal embryonic kidney (HEK293) cells. Notably, compound YNU-4f bearing QL1e and QL3a ligands showed a more pronounced antiproliferative effect against LC549 cells (IC50 = 1.75 ± 0.09 µM) with high intrinsic selectivity toward LC549 cancer cells than YNU-4a-YNU-4e, H-QL1a-H-QL1e, cisplatin (PDD), YNU-4g-YNU-4k, and H-QL3a-H-QL3c. Additionally, a colocalization assay analysis of YNU-4e and YNU-4f showed that these two ruthenium(II/III) compounds were subcellularly accumulated in the mitochondria and other regions of the cytoplasm, where they induce mitophagy, adenosine triphosphate (ATP) reduction, mitochondrial respiratory chain complex I/IV(RC1/RC4) inhibition, and mitochondrial dysfunction. Accordingly, compounds YNU-4a-YNU-4k can be regarded as mitophagy inductors for the eradication of cisplatin-resistant LC549 cancer cells.

Anti-CTLA-4 m2a Antibody Exacerbates Cardiac Injury in Experimental Autoimmune Myocarditis Mice By Promoting Ccl5-Neutrophil Infiltration.

The risk for suffering immune checkpoint inhibitors (ICIs)-associated myocarditis increases in patients with pre-existing conditions and the mechanisms remain to be clarified. Spatial transcriptomics, single-cell RNA sequencing, and flow cytometry are used to decipher how anti-cytotoxic T lymphocyte antigen-4 m2a antibody (anti-CTLA-4 m2a antibody) aggravated cardiac injury in experimental autoimmune myocarditis (EAM) mice. It is found that anti-CTLA-4 m2a antibody increases cardiac fibroblast-derived C-X-C motif chemokine ligand 1 (Cxcl1), which promots neutrophil infiltration to the myocarditic zones (MZs) of EAM mice via enhanced Cxcl1-Cxcr2 chemotaxis. It is identified that the C-C motif chemokine ligand 5 (Ccl5)-neutrophil subpopulation is responsible for high activity of cytokine production, adaptive immune response, NF-κB signaling, and cellular response to interferon-gamma and that the Ccl5-neutrophil subpopulation and its-associated proinflammatory cytokines/chemokines promoted macrophage (Mφ) polarization to M1 Mφ. These altered infiltrating landscape and phenotypic switch of immune cells, and proinflammatory factors synergistically aggravated anti-CTLA-4 m2a antibody-induced cardiac injury in EAM mice. Neutralizing neutrophils, Cxcl1, and applying Cxcr2 antagonist dramatically alleviates anti-CTLA-4 m2a antibody-induced leukocyte infiltration, cardiac fibrosis, and dysfunction. It is suggested that Ccl5-neutrophil subpopulation plays a critical role in aggravating anti-CTLA-4 m2a antibody-induced cardiac injury in EAM mice. This data may provide a strategic rational for preventing/curing ICIs-associated myocarditis.

Pulmonary function test-related prognostic models in non-small cell lung cancer patients receiving neoadjuvant chemoimmunotherapy.

Background: This study aimed to establish a comprehensive clinical prognostic risk model based on pulmonary function tests. This model was intended to guide the evaluation and predictive management of patients with resectable stage I-III non-small cell lung cancer (NSCLC) receiving neoadjuvant chemoimmunotherapy. Methods: Clinical pathological characteristics and prognostic survival data for 175 patients were collected. Univariate and multivariate Cox regression analyses, and least absolute shrinkage and selection operator (LASSO) regression analysis were employed to identify variables and construct corresponding models. These variables were integrated to develop a ridge regression model. The models' discrimination and calibration were evaluated, and the optimal model was chosen following internal validation. Comparative analyses between the risk scores or groups of the optimal model and clinical factors were conducted to explore the potential clinical application value. Results: Univariate regression analysis identified smoking, complete pathologic response (CPR), and major pathologic response (MPR) as protective factors. Conversely, T staging, D-dimer/white blood cell ratio (DWBCR), D-dimer/fibrinogen ratio (DFR), and D-dimer/minute ventilation volume actual ratio (DMVAR) emerged as risk factors. Evaluation of the models confirmed their capability to accurately predict patient prognosis, exhibiting ideal discrimination and calibration, with the ridge regression model being optimal. Survival analysis demonstrated that the disease-free survival (DFS) in the high-risk group (HRG) was significantly shorter than in the low-risk group (LRG) (P=2.57×10-13). The time-dependent receiver operating characteristic (ROC) curve indicated that the area under the curve (AUC) values at 1 year, 2 years, and 3 years were 0.74, 0.81, and 0.79, respectively. Clinical correlation analysis revealed that men with lung squamous cell carcinoma or comorbid chronic obstructive pulmonary disease (COPD) were predominantly in the LRG, suggesting a better prognosis and potentially identifying a beneficiary population for this treatment combination. Conclusion: The prognostic model developed in this study effectively predicts the prognosis of patients with NSCLC receiving neoadjuvant chemoimmunotherapy. It offers valuable predictive insights for clinicians, aiding in developing treatment plans and monitoring disease progression.

Effects of buccal acupuncture on postoperative analgesia in elderly patients undergoing laparoscopic radical gastrectomy: a randomized controlled trial.

Objective: This study aimed to evaluate the efficacy and safety of buccal acupuncture on postoperative analgesia, perioperative stress response and adverse events in elderly patients undergoing laparoscopic radical gastrectomy. Methods: It was a prospective, outcome assessor-blinded, randomized controlled trial, involving 90 patients aged 65-80 years who were treated with an elective laparoscopic radical gastrectomy. They were randomly assigned to buccal acupuncture group (Group B) and control group (Group C). Buccal acupuncture was applied to patients of Group B before the induction of general anesthesia, while no additional application was given to those in Group C. Patient-controlled intravenous analgesia (PCIA) with sufentanil was postoperatively performed in both groups. Sufentanil consumption and the Visual Analog Scale (VAS) score within 48 h postoperatively were assessed as primary outcomes. Secondary outcomes included peripheral levels of stress markers, intraoperative consumptions of anesthetic drugs and postoperative recovery. Results: Patients in Group B presented significantly lower VAS scores within 24 h and less consumption of sufentanil within 48 h postoperatively (both p < 0.01). The awaking time, time to extubation and length of stay were significantly shorter in Group B than in Group C (p = 0.005, 0.001 and 0.028, respectively). Compared with Group C, stress response and inflammatory response within 24 h postoperatively were also significantly milder in Group B. Conclusion: The use of buccal acupuncture before general anesthesia induction favors the postoperative analgesic effect and recovery in elderly patients undergoing laparoscopic radical gastrectomy, the mechanism of which involves relieving postoperative stress response and inflammatory response. Clinical trial registration: This study was registered in the Chinese Clinical Trial Registry (www.chictr.org.cn) on 15/06/2023 (ChiCTR2300072500).

SARS-CoV-2 spike protein potentiates platelet aggregation via upregulating integrin αIIbß3 outside-in signaling pathway.

Platelet hyperreactivity is one of the crucial causes of coagulative disorders in patients with COVID-19. Few studies have indicated that integrin αIIbß3 may be a potential target for spike protein binding to platelets. This study aims to investigate whether spike protein interacts with platelet integrin αIIbß3 and upregulates outside-in signaling to potentiate platelet aggregation. In this study, we found that spike protein significantly potentiated platelet aggregation induced by different agonists and platelet spreading in vitro. Mechanism studies revealed that spike protein upregulated the outside-in signaling, such as increased thrombin-induced phosphorylation of ß3, c-Src. Moreover, using tirofiban to inhibit spike protein binding to αIIbß3 or using PP2 to block outside-in signaling, we found that the potentiating effect of spike protein on platelet aggregation was abolished. These results demonstrate that SARS-CoV-2 spike protein directly enhances platelet aggregation via integrin αIIbß3 outside-in signaling, and suggest a potential target for platelet hyperreactivity in patients with COVID-19. HIGHLIGHTS: • Spike protein potentiates platelet aggregation and upregulates αIIbß3 outside-in signaling. • Spike protein interacts with integrin αIIbß3 to potentiate platelet aggregation. • Blocking outside-in signaling abolishes the effect of spike protein on platelets.

Transcriptome sequencing of garlic reveals key genes related to the heat stress response.

With global warming, heat stress has become an important factor that seriously affects crop yield and quality. Therefore, understanding plant responses to heat stress is important for agricultural practice, but the molecular mechanism of high-temperature tolerance in garlic remains unclear. In this study, 'Xusuan No. 6' was used as the experimental material. After heat stress for 0 (CK), 2 and 24 h, transcriptome sequencing was used to screen metabolic pathways and differentially expressed genes (DEGs) closely related to heat stress and was further verified by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 86,110 unigenes obtained from the raw transcriptome sequencing data were spliced. After 2 h of heat treatment, the expression levels of 8898 genes increased, and 3829 genes were decreased in leaves. After 24 h, the expression levels of 7167 genes were upregulated, and 3176 genes were downregulated. Gene Ontology enrichment analysis showed that DEGs were mainly enriched in seven categories: cellular processes, metabolic processes, binging, catalytic activity, cellular anatomical entity and protein-containing complex response to stimulus. Kyoto Encyclopedia of Genes and Genomes pathway enrichment showed that DEGs are involved in protein processing in the endoplasmic reticulum, plant hormone signal transduction, phenylpropanoid biosynthesis, and photosynthetic antenna proteins. Six genes were selected and further verified by qRT-PCR. In this study, the full-length transcriptome of garlic was constructed, and the regulatory genes related to the heat resistance of garlic were studied. Taken together, these findings can provide a theoretical basis for the cloning of heat resistance genes in garlic and for the analysis of heat resistance mechanisms.

Compare clinical efficacy and safety of neoadjuvant therapy and neoadjuvant chemoradiotherapy for locally advanced rectal cancer: Meta-analysis.

BACKGROUND: To compare the efficacy and safety of total neoadjuvant therapy (TNT) and neoadjuvant chemoradiotherapy (nCRT) in the treatment of middle and low locally advanced rectal cancer. Our study will systematically collect and integrate studies to evaluate the ability of these two treatments to improve tumor shrinkage rates, surgical resection rates, tumor-free survival, and severe adverse events. AIM: To provide clinicians and patients with more reliable treatment options to optimize treatment outcomes and quality of life for patients with locally advanced rectal cancer by comparing the advantages and disadvantages of the two treatment options. METHODS: A full search of all clinical studies on the effectiveness and safety of TNT and nCRT for treating locally advanced rectal cancer identified in Chinese (CNKI, Wanfang, China Biomedical Literature Database) and English (PubMed, Embase) databases was performed. Two system assessors independently screened the studies according to the inclusion and exclusion criteria. Quality evaluation and data extraction were performed for the included literature. We used RevMan 5.3 software to perform a meta-analysis of the pathologic complete response (pCR) rate, T stage degradation rate, resection 0 (R0) rate, anal grade 3/4 acute toxicity rate, perioperative complications, overall survival (OS), and disease-free survival (DFS) in the TNT and nCRT groups. RESULTS: Finally, 14 studies were included, six of which were randomized controlled studies. A total of 3797 patients were included, including 1865 in the TNT group and 1932 in the nCRT group. The two sets of baseline data were comparable. The results of the meta-analysis showed that the pCR rate [odds ratio (OR) = 1.57, 95% confidence interval (CI): 1.30-1.90, P < 0.00001], T stage degradation rate (OR = 2.16, 95%CI: 1.63-2.57, P < 0.00001), and R0 resection rate (OR = 1.42, 95%CI: 1.09-1.85, P = 0.009) were significantly greater in the nCRT group than in the nCRT group. There was no significant difference in the incidence of grade 3/4 acute toxicity or perioperative complications between the two groups. The 5-year OS [hazard ratio (HR) = 0.84, 95%CI: 0.69-1.02, P = 0.08] and DFS (HR = 0.94, 95%CI: 0.03-1.39, P = 0.74) of the TNT group were similar to those of the nCRT group. CONCLUSION: TNT has greater clinical efficacy and safety than nCRT in the treatment of locally advanced rectal cancer.

Olverembatinib combined with inotuzumab ozogamicin in relapsed refractory Philadelphia chromosome-positive acute lymphoblastic leukemia: A case report.

RATIONALE: Patients with relapsed and refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with the T315I mutation are at higher risk of relapse and have shorter overall survival. PATIENT CONCERNS: A 31-year-old man presented to the hematology department with intermittent fever and pancytopenia. He was diagnosed with Ph+ acute lymphoblastic leukemia and experienced 2 relapses during treatment. A drug-resistant T315I mutation was detected in the ABL kinase region during review. DIAGNOSES: Morphological examination of the bone marrow revealed approximately 93.5% lymphoid blast. Flow cytometric analysis confirmed the diagnosis of common B-cell ALL with the following phenotype: CD34, CD45dim, CD19, CD10, cCD79a, CD58dim, CD81dim, cTdT, HLA-DR, CD22dim, CXCR4, CD33dim, CD20, CD25, CD13, CD123. The examination of the ABL kinase region mutation suggested a T315I mutation. INTERVENTIONS: Olverembatinib, a third-generation TKI drug, was administered in combination with inotuzumab ozogamicin to treat the disease. OUTCOMES: The patient achieved morphological remission with a negative flow cytometry MRD test, and the quantification of BCR-ABL transcripts was 0% after 1 cycle of therapy. LESSONS: The third-generation TKI olverembatinib has been proven to be effective in CML patients with the T315I mutation, and it may also be effective in Ph+ acute lymphoblastic leukemia. Some new immune drugs have also shown improvement in the remission rate. Combination therapy with olverembatinib and Ino can achieve a complete molecular response in patients with relapsed and refractory Ph+ ALL with the T315I mutation.