A 12-Vertex Metallacarborane of Silver(I).

The discovery of ferrocene in 1951 was a significant landmark in the field of organometallic chemistry, and since then, numerous sandwich- or half-sandwich metallic complexes have been reported. However, silver stands as an intriguing exception in this regard, and knowledge of its bonding situation has remained undisclosed. Herein, unprecedented 12-vertex metallacarboranes of Ag(I) (2a and 2b) were synthesized through the reaction of sodium hexamethyldisilazide (NaHMDS) with the mixture of nido-C2B9 carborane anion-supported N-heterocyclic carbene precursors (1a and 1b) and [Ag(PPh3)Cl]4. The X-ray structural analysis of the resulting metallacarboranes revealed a unique "slipped" half-sandwich structure, which is a rarity among cyclopentadienyl analogues. DFT calculations provided insights into the asymmetric π-interactions between the pentagonal C2B3 face and the silver ion.

Neural Development and Repair Induced by Femtosecond Laser Stimulation.

Dendritic spines function as postsynaptic sites, receiving excitatory signals from presynaptic axons. The synaptic plasticity of spines underlies the refinement of neuronal circuits. Neural cognitive disorders are commonly associated with the impairment and elimination of dendritic spines. In this study, we report an all-optical method to activate dendritic spine growth and regeneration by a single short flash of femtosecond laser stimulation. The inhibited development and loss of spines can be rescued by a transient illumination of the laser inside a micrometer region of the soma by activating the extracellular signal-regulated kinase (ERK) signaling pathway. The rescued neurons exhibit function. Hence we provide a potential noninvasive method for the regeneration of dendritic spines.

Giant pulmonary artery aneurysm associated with SARS-CoV-2 infection and Actinomyces odontolyticus sepsis: A case report.

Giant septic pulmonary artery aneurysms (PAAs) are rare but important entities, with few cases having been reported worldwide. Early diagnosis and prompt treatment are crucial in the management of such cases. We report a 56-year-old female patient presenting with fatigue, nausea and vomiting who was first diagnosed with diabetic ketoacidosis (DKA) and developed life-threatening giant infectious PAA secondary to SARS-CoV-2 infection and Actinomyces odontolyticus sepsis. The patient did not develop any specific symptoms, and enhanced computed tomography (CT) revealed a massive PAA of 5.6 × 4.9 cm in size at the left pulmonary hilar with normal pulmonary artery (PA) pressures. After multidisciplinary discussion and after considering the critical condition accompanied by sepsis increased the risk of surgery, endovascular treatment was the first therapy of choice for the patient; nevertheless, the patient ultimately opted for hospice care. This case report aims to raise awareness of PAAs, which are rare but potentially fatal complications of infectious diseases such as COVID-19 pneumonia and Actinomyces odontolyticus sepsis.

Robotic versus laparoscopic distal gastrectomy for gastric cancer: A systematic review and meta-analysis.

Distal gastrectomy (DG) with lymph node dissection for gastric cancer is routinely performed. In this meta-analysis, we present an updated overview of the perioperative and oncological outcomes of laparoscopic DG (LDG) and robotic DG (RDG) to compare their safety and overall outcomes in patients undergoing DG. An extensive search was conducted using the MEDLINE, EMBASE, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials from the establishment of the database to June 2023 for randomized clinical trials comparing RDG and LDG. The primary outcome was operative results, postoperative recovery, complications, adequacy of resection, and long-term survival. We identified twenty studies, evaluating 5,447 patients (1,968 and 3,479 patients treated with RDG and LDG, respectively). We observed no significant differences between the two groups in terms of the proximal resection margin, number of dissected lymph nodes, major complications, anastomosis site leakage, time to first flatus, and length of hospital stay. The RDG group had a longer operative time (P < 0.00001), lesser bleeding (P = 0.0001), longer distal resection margin (P = 0.02), earlier time to oral intake (P = 0.02), fewer overall complications (P = 0.004), and higher costs (P < 0.0001) than the LDG group. RDG is a promising approach for improving LDG owing to acceptable complications and the possibility of radical resection. Longer operative times and higher costs should not prevent researchers from exploring new applications of robotic surgery.

DGK5ß-derived phosphatidic acid regulates ROS production in plant immunity by stabilizing NADPH oxidase.

In plant immunity, phosphatidic acid (PA) regulates reactive oxygen species (ROS) by binding to respiratory burst oxidase homolog D (RBOHD), an NADPH oxidase responsible for ROS production. Here, we analyze the influence of PA binding on RBOHD activity and the mechanism of RBOHD-bound PA generation. PA binding enhances RBOHD protein stability by inhibiting vacuolar degradation, thereby increasing chitin-induced ROS production. Mutations in diacylglycerol kinase 5 (DGK5), which phosphorylates diacylglycerol to produce PA, impair chitin-induced PA and ROS production. The DGK5 transcript DGK5ß (but not DGK5α) complements reduced PA and ROS production in dgk5-1 mutants, as well as resistance to Botrytis cinerea. Phosphorylation of S506 residue in the C-terminal calmodulin-binding domain of DGK5ß contributes to the activation of DGK5ß to produce PA. These findings suggest that DGK5ß-derived PA regulates ROS production by inhibiting RBOHD protein degradation, elucidating the role of PA-ROS interplay in immune response regulation.

Integrated Virtual Screening and Validation toward Potential HPPD Inhibition Herbicide.

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) is one of the most widely studied herbicide targets and has gained significant attention. To identify potential effective HPPD inhibitors, a rational multistep virtual screening workflow was built, which included CBP models (based on the receptor-ligand interactions in the crystal complex), Hypogen models with activity prediction ability (according to the derivation of structure-activity relationships from a set of molecules with reported activity values), and a consensus docking procedure (consisting of LibDock, Glide, and CDOCKER). About 1 million molecules containing diketone or ß-keto-enol substructures were filtered by Lipinski's rules, CBP model, and Hypogen model. A total of 12 compounds with similar docking postures were generated by consensus docking. Eventually, four molecules were screened based on the specific binding pattern and affinity of the HPPD inhibitor. The biological evaluation in vivo displayed that compounds III-1 and III-2 exhibited comparable herbicidal activity to isoxaflutole and possessed superior safety on various crops (wheat, rice, sorghum, and maize). The ADMET prediction (absorption, distribution, metabolism, excretion, and toxicity) showed that compound III possessed relatively good toxicological results. This work provides a theoretical basis and valuable reference for the virtual screening and molecular design of novel HPPD inhibition herbicides.

Effects of ulinastatin combined with dexmedetomidine on cognitive dysfunction and emergence agitation in elderly patients who underwent total hip arthroplasty.

BACKGROUND: With the continuous growth of the modern elderly population, the risk of fracture increases. Hip fracture is a common type of fracture in older people. Total hip arthroplasty (THA) has significant advantages in relieving chronic pain and promoting the recovery of hip joint function. AIM: To investigate the effect of ulinastatin combined with dexmedetomidine (Dex) on the incidences of postoperative cognitive dysfunction (POCD) and emergence agitation in elderly patients who underwent THA. METHODS: A total of 397 patients who underwent THA from February 2019 to August 2022. We conducted a three-year retrospective cohort study in Shaanxi Provincial People's Hospital. Comprehensive demographic data were obtained from the electronic medical record system. We collected preoperative, intraoperative, and postoperative data. One hundred twenty-nine patients who were administered Dex during the operation were included in the Dex group. One hundred fifty patients who were intravenously injected with ulinastatin 15 min before anesthesia induction were included in the ulinastatin group. One hundred eighteen patients who were administered ulinastatin combined with Dex during the operation were included in the Dex + ulinastatin group. The patients' perioperative conditions, hemodynamic indexes, postoperative Mini-Mental State Examination (MMSE) scores, Ramsay score, incidence of POCD, and serum inflammatory cytokines were evaluated. RESULTS: There was a significant difference in the 24 h visual analogue scale score among the three groups, and the score in the Dex + ulinastatin group was the lowest (P < 0.05). Compared with the Dex and ulinastatin group, the MMSE scores of the Dex + ulinastatin group were significantly increased at 1 and 7 d after the operation (all P < 0.05). Compared with those in the Dex and ulinastatin groups, incidence of POCD, levels of serum inflammatory cytokines in the Dex + ulinastatin group were significantly decreased at 1 and 7 d after the operation (all P < 0.05). The observer's assessment of the alertness/sedation score and Ramsay score of the Dex + ulinastatin group were significantly different from those of the Dex and ulinastatin groups on the first day after the operation (all P < 0.05). CONCLUSION: Ulinastatin combined with Dex can prevent the occurrence of POCD and emergence agitation in elderly patients undergoing THA.

Design, Synthesis, and Biological Evaluation of Novel Purine Derivatives as Herbicide Safeners.

Mesosulfuron-methyl, an inhibitor of acetolactate synthase (ALS), has been extensively used in wheats. However, it can damage wheat (Triticum aestivum) and even lead to crop death. Herbicide safeners selectively shield crops from such damage without compromising weed control. To mitigate the phytotoxicity of mesosulfuron-methyl in crops, several purine derivatives were developed based on active substructure splicing. The synthesized title compounds underwent thorough characterization using infrared spectroscopy, 1H nuclear magnetic resonance (1H NMR), 13C nuclear magnetic resonance (13C NMR), and high-resolution mass spectrometry. We evaluated chlorophyll and glutathione contents as well as various enzyme activities to evaluate the safer activity of these compounds. Compounds III-3 and III-7 exhibited superior activity compared with the safener mefenpyr-diethyl. Molecular structure analysis, along with predictions of absorption, distribution, metabolism, excretion, and toxicity, indicated that compound III-7 shared pharmacokinetic traits with the commercial safener mefenpyr-diethyl. Molecular docking simulations revealed that compound III-7 competitively bound to the ALS active site with mesosulfuron-methyl, elucidating the protective mechanism of the safeners. Overall, this study highlights purine derivatives as potential candidates for novel safener development.

Deciphering the population structure and genetic basis of growth traits from whole-genome resequencing of the leopard coral grouper ( Plectropomus leopardus).

The leopard coral grouper ( Plectropomus leopardus) is a species of significant economic importance. Although artificial cultivation of P. leopardus has thrived in recent decades, the advancement of selective breeding has been hindered by the lack of comprehensive population genomic data. In this study, we identified over 8.73 million single nucleotide polymorphisms (SNPs) through whole-genome resequencing of 326 individuals spanning six distinct groups. Furthermore, we categorized 226 individuals with high-coverage sequencing depth (≥14×) into eight clusters based on their genetic profiles and phylogenetic relationships. Notably, four of these clusters exhibited pronounced genetic differentiation compared with the other populations. To identify potentially advantageous loci for P. leopardus, we examined genomic regions exhibiting selective sweeps by analyzing the nucleotide diversity ( θπ) and fixation index ( F ST) in these four clusters. Using these high-coverage resequencing data, we successfully constructed the first haplotype reference panel specific to P. leopardus. This achievement holds promise for enabling high-quality, cost-effective imputation methods. Additionally, we combined low-coverage sequencing data with imputation techniques for a genome-wide association study, aiming to identify candidate SNP loci and genes associated with growth traits. A significant concentration of these genes was observed on chromosome 17, which is primarily involved in skeletal muscle and embryonic development and cell proliferation. Notably, our detailed investigation of growth-related SNPs across the eight clusters revealed that cluster 5 harbored the most promising candidate SNPs, showing potential for genetic selective breeding efforts. These findings provide a robust toolkit and valuable insights into the management of germplasm resources and genome-driven breeding initiatives targeting P. leopardus.

Deciphering the molecular landscape of rheumatoid arthritis offers new insights into the stratified treatment for the condition.

Background: For Rheumatoid Arthritis (RA), a long-term chronic illness, it is essential to identify and describe patient subtypes with comparable goal status and molecular biomarkers. This study aims to develop and validate a new subtyping scheme that integrates genome-scale transcriptomic profiles of RA peripheral blood genes, providing a fresh perspective for stratified treatments. Methods: We utilized independent microarray datasets of RA peripheral blood mononuclear cells (PBMCs). Up-regulated differentially expressed genes (DEGs) were subjected to functional enrichment analysis. Unsupervised cluster analysis was then employed to identify RA peripheral blood gene expression-driven subtypes. We defined three distinct clustering subtypes based on the identified 404 up-regulated DEGs. Results: Subtype A, named NE-driving, was enriched in pathways related to neutrophil activation and responses to bacteria. Subtype B, termed interferon-driving (IFN-driving), exhibited abundant B cells and showed increased expression of transcripts involved in IFN signaling and defense responses to viruses. In Subtype C, an enrichment of CD8+ T-cells was found, ultimately defining it as CD8+ T-cells-driving. The RA subtyping scheme was validated using the XGBoost machine learning algorithm. We also evaluated the therapeutic outcomes of biological disease-modifying anti-rheumatic drugs. Conclusions: The findings provide valuable insights for deep stratification, enabling the design of molecular diagnosis and serving as a reference for stratified therapy in RA patients in the future.

New alkaloids from Stemona tuberosa and structural revision of tuberostemonols P and R.

Three Stemona alkaloids named stemotuberines A-C (1-3) with unique C17N frameworks, presumably formed by elimination of the C-11-C-15 lactone ring of the stichoneurine skeleton, were isolated from the roots of Stemona tuberosa. Their structures were elucidated by spectroscopic analysis, X-ray diffraction, and computational methods. Compounds 2 and 3 showed inhibition (IC50 values of 37.1 and 23.2 µM, respectively) against LPS-induced nitric oxide production in RAW 264.7 cells. In addition, concern was expressed about the reported plant origin (S. sessilifolia) of the recently described alkaloids tuberostemonols O-R (4-7), which should be S. tuberosa. NMR calculations indicated structural misassignment of these compounds except for 6. Isolation of tuberostemonol P (5) from our material of S. tuberosa allowed for a close examination of the spectroscopic data leading to the revised structure 5a. Tuberostemonol R (7) was found to have identical 1H and 13C NMR data to the well-known alkaloid croomine, and therefore its structure including relative stereochemistry must be revised as 7a.

Predictive value of frailty assessment tools in patients undergoing surgery for gastrointestinal cancer: An observational cohort study.

BACKGROUND: Few studies have simultaneously compared the predictive value of various frailty assessment tools for outcome measures in patients undergoing gastrointestinal cancer surgery. Therefore, it is difficult to determine which assessment tool is most relevant to the prognosis of this population. AIM: To investigate the predictive value of three frailty assessment tools for patient prognosis in patients undergoing gastrointestinal cancer surgery. METHODS: This single-centre, observational, prospective cohort study was conducted at the Affiliated Lianyungang Hospital of Xuzhou Medical University from August 2021 to July 2022. A total of 229 patients aged ≥ 18 years who underwent surgery for gastrointestinal cancer were included in this study. We collected baseline data on the participants and administered three scales to assess frailty: The comprehensive geriatric assessment (CGA), Fried phenotype and FRAIL scale. The outcome measures were the postoperative severe complications and increased hospital costs. RESULTS: The prevalence of frailty when assessed with the CGA was 65.9%, 47.6% when assessed with the Fried phenotype, and 34.9% when assessed with the FRAIL scale. Using the CGA as a reference, kappa coefficients were 0.398 for the Fried phenotype and 0.291 for the FRAIL scale (both P < 0.001). Postoperative severe complications and increased hospital costs were observed in 29 (12.7%) and 57 (24.9%) patients, respectively. Multivariate logistic analysis confirmed that the CGA was independently associated with increased hospital costs (odds ratio = 2.298, 95% confidence interval: 1.044-5.057; P = 0.039). None of the frailty assessment tools were associated with postoperative severe complications. CONCLUSION: The CGA was an independent predictor of increased hospital costs in patients undergoing surgery for gastrointestinal cancer.