In-situ surface reconstruction of Co-based imidazole zeolite framework by Mo etching for superior water oxidation.

Although zeolitic imidazolate frameworks (ZIFs) possess the merits of orderly porosity, high permeability, and easy functionalization, the transformation of ZIFs into the real active species and the promotion of the catalytic efficiency and stability are still challenging. Herein, CoMo-based three-dimensional (3D) hollow nanocages composed of interconnected nanosheets are fabricated by in-situ etching metal-organic framework (ZIF-67) under the aid of MoO42-. X-ray photoelectron spectroscopy (XPS) and in-situ Raman confirm that Mo leaching can accelerate surface reconstruction and generate CoOOH active sites after continuous oxidation. Benefiting from the nanostructure and electronic properties after surface reconstruction, the engineered CoMo-30 exhibits the lowest overpotential of 280 mV at 30 mA cm-2 and robust stability over 110 h in 1 M KOH media for oxygen evolution reaction (OER), which significantly surpasses the other counterparts and commercial RuO2. Density functional theory (DFT) calculations indicate that CoMo-30 has a lower free energy of *O â†’ *OOH as rate determining step (RDS), suggesting that CoOOH sites play a crucial role in enhancing the activity and kinetics of OER. This work provides valuable insights into the rational design of hollow structures and the structure-composition-activity relationship during the electrochemical reaction process.

Fate and mass budget of microplastic in the Beibu Gulf, the northern South China sea.

This study investigated the distribution, abundance, and mass budget of microplastics (MPs) in the Beibu Gulf, Northern South China Sea, focusing on their ecological significance and anthropogenic influence. Microplastics were found in all water and sediment samples, with concentrations in surface water ranging from 0.10 to 0.89 items/m³, and in bottom water from 0 to 0.85 items/m³. Sediment samples exhibited higher levels, ranging from 13.12 to 155.59 items/kg. The spatial distribution revealed higher concentrations along the northern Gulf and Guangxi Province, suggesting significant human influence from coastal activities, such as mariculture and industrial discharges. The study utilized both field data and a mass balance box model to estimate the MPs mass budget, revealing that oceanic flow and riverine discharge are major contributors, accounting for 49% and 52% of MPs, while Atmospheric deposition and sedimentation represents 8% and 1%, respectively. The inventory estimation calculated that 0.24 tons of MPs exist in the water column, and 137 tons in the sediment, emphasizing the substantial environmental burden posed by these pollutants. The significance of this research lies in its comprehensive assessment of MPs in a semi-enclosed gulf, providing critical insight into the role of coastal and hydrodynamic processes in MP distribution. This study highlights the urgent need for better waste management practices in coastal regions to mitigate microplastic pollution and its detrimental effects on marine ecosystems.

Neurological activation during verbal fluency task and resting-state functional connectivity abnormalities in obsessive-compulsive disorder: a functional near-infrared spectroscopy study.

Objective: This study aims to investigate the activation of frontotemporal functional brain areas in patients with Obsessive-Compulsive Disorder (OCD) during a Verbal Fluency Task (VFT), and to compare their brain functional connectivity in a resting state with that of healthy controls. The goal is to deepen our understanding of the neuropathological mechanisms underlying OCD. Methods: 32 patients with OCD and 32 controls matched for age, gender, handedness, and years of education participated in this study, they were divided into OCD group and healthy comtrol group. We conducted VFT task tests and 10-minute resting state tests on both groups by using functional Near-Infrared Spectroscopy (fNIRS). The VFT was utilized to assess the activation (beta values) and the integral and centroid values of the frontal and bilateral temporal lobes, including brain areas BA9 and 46 (dorsolateral prefrontal cortex), BA10 (frontal pole), BA45 (inferior frontal gyrus), BA21 (middle temporal gyrus), and BA22 (superior temporal gyrus). We evaluated the functional connectivity levels of these areas during the resting state. Differences in these measures between OCD patients and healthy controls were analyzed using two-sample independent t-tests and non-parametric Mann-Whitney U tests. Results: During VFT, OCD had smaller integral values(z=5.371, p<0.001; t=4.720, p<0.001), and larger centroid values(t=-2.281, p=0.026; z=-2.182, p=0.029) compared to healthy controls, along with a reduced number of activated channels detected by fNIRS. Additionally, activation values (ß) in various functional brain areas, including BA9, BA46, BA10, BA45, BA21, and BA22, were significantly lower in the OCD group (all p< 0.01). In the resting state, notable disparities in functional connectivity were observed between the inferior frontal gyrus (IFG) and dorsolateral prefrontal cortex (DLPFC) in the OCD group, in comparison to the control group. Specifically, there was a significant increase in connectivity between the left IFG and right DLPFC, suggesting the presence of altered connectivity patterns in these areas. Conclusions: The study highlights significant disparities in neural activation and functional connectivity between OCD patients and healthy controls during VFT. Specifically, reduced activation was noted in the frontal and bilateral temporal lobes of OCD patients, alongside alterations in resting-state functional connectivity between the IFG and DLPFC. These findings contribute to our understanding of the neurobiological underpinnings of OCD and may guide future therapeutic strategies.

Influence of suspended particulate matters on P dynamics and eutrophication in the highly turbid estuary: A case study in Hangzhou Bay, China.

Phosphorus (P) is an essential biogenic element in ecosystems; but excessive or insufficient P in coastal waters caused by human activities has led to serious ecological issues. However, the understanding of the dynamic processes of different P forms in high turbidity estuaries/bays, as well as their impact on eutrophication and coastal algal blooms, is still relatively limited. To address this issue, we analyzed P dynamics and their impact on eutrophication in Hangzhou Bay (HZB), which is typical of eutrophic and turbid bay worldwide. The concentration of particulate P (PTP) was 3-5 times higher than that of dissolved inorganic phosphorus (DIP). Seasonal sediment resuspension led to the accumulation of suspended particulate matter (SPM) and PTP with regional variation, both maintaining DIP concentrations above 1 µmol/L within the bay. Furthermore, 3000 tons of bioavailable P were retained in the fine-grained SPM, with the potential for outward transport, fueling subsequent harmful algal blooms. A comparative analysis of global coastal waters highlighted that different turbidity levels significantly affect P cycling. Therefore, understanding the relationship between SPM and P in highly turbid waters is crucial for effective management of eutrophication.

The efficacy of the food-grade antimicrobial xanthorrhizol against Staphylococcus aureus is associated with McsL channel expression.

Background: The emergence and spread of multidrug-resistant Staphylococcus aureus strains demonstrates the urgent need for new antimicrobials. Xanthorrhizol, a plant-derived sesquiterpenoid compound, has a rapid killing effect on methicillin-susceptible strains and methicillin-resistant strains of S. aureus achieving the complete killing of staphylococcal cells within 2 min using 64 µg/mL xanthorrhizol. However, the mechanism of its action is not yet fully understood. Methods: The S. aureus cells treated with xanthorrhizol were studied using optical diffraction tomography. Activity of xanthorrhizol against the wild-type and mscL null mutant of S. aureus ATCC 29213 strain was evaluated in the time-kill assay. Molecular docking was conducted to predict the binding of xanthorrhizol to the SaMscL protein. Results: Xanthorrhizol treatment of S. aureus cells revealed a decrease in cell volume, dry weight, and refractive index (RI), indicating efflux of the cell cytoplasm, which is consistent with the spontaneous activation of the mechanosensitive MscL channel. S. aureus ATCC 29213ΔmscL was significantly more resistant to xanthorrhizol than was the wild-type strain. Xanthorrhizol had an enhanced inhibitory effect on the growth and viability of exponentially growing S. aureus ATCC 29213ΔmscL cells overexpressing the SaMscL protein and led to a noticeable decrease in their viability in the stationary growth phase. The amino acid residues F5, V14, M23, A79, and V84 were predicted to be the residues of the binding pocket for xanthorrhizol. We also showed that xanthorrhizol increased the efflux of solutes such as K+ and glutamate from S. aureus ATCC 29213ΔmscL cells overexpressing SaMscL. Xanthorrhizol enhanced the antibacterial activity of the antibiotic dihydrostreptomycin, which targets the MscL protein. Conclusion: Our findings indicate that xanthorrhizol targets the SaMscL protein in S. aureus cells and may have important implications for the development of a safe antimicrobial agent.

Coordination Environment and Distance Optimization of Dual Single Atoms on Fluorine-Doped Carbon Nanotubes for Chlorine Evolution Reaction.

The chlorine evolution reaction (CER) is a crucial anode reaction in the chlor-alkali industrial process. Precious metal-based dimensionally stable anodes (DSA) are commonly used as catalysts for CER but are constrained by their high cost and low selectivity. Herein, a Pt dual singe-atom catalyst (DSAC) dispersed on fluorine-doped carbon nanotubes (F-CNTs) is designed for an efficient and robust CER process. The prepared Pt DSAC demonstrates excellent CER activity with a low overpotential of 21 mV to achieve a current density of 10 mA cm-2 and a remarkable mass activity of 3802.6 A gpt -1 at an overpotential around 30 mV, outperforming those of commercial DSA and Pt single-atom catalyst. The excellent CER performance of Pt DSAC is attributed to the high atomic utilization and improved intrinsic activity. Notably, introducing fluorine atoms on CNTs increases the oxidation and chlorination resistance of Pt DSAC, and reduces the demetalization ratio of Pt atoms, resulting in excellent long-term CER stability. Theoretical calculations reveal that several Pt DSAC configurations with optimized first-shell ligands and interatomic distance display lower energy barriers for Cl intermediates generation and weaker ionic Pt-Cl bond interaction, which are favorable for the CER process.

Decoupling of high-resolution surface pH and DO reveals temporal algal bloom dynamics on the East China Sea.

The stoichiometric ratio between seawater CO2 and dissolved oxygen (DO) during phytoplankton metabolism holds significant importance in evaluating ecological and biogeochemical processes. We collected high-resolution underway temperature, salinity, DO, and pH data in the East China Sea inner shelf in May 2017. Our results revealed high pH (8.36) and supersaturated DO (171 %) in the outer Changjiang Estuary, indicating the occurrence of an algal bloom event. They were significantly correlated with a regression slope of 0.0029, which roughly followed the Redfield ratio. In contrast, a much higher ratio (0.0088) manifested in a low-salinity patch on north of the Changjiang Estuary, featuring a pH of 8.40 and oxygen saturation of approximately 123 %. The substantially faster air-sea equilibrium rate of O2 than CO2 probably caused such decoupling, offering insight into the temporal evolutions of algal bloom. Theoretically, a steeper regression slope implies an earlier onset of algal bloom. An end-member mixing model was constructed to exclude the physical mixing influences on dissolved inorganic carbon (ΔDIC) and DO (ΔDO). Furthermore, we conducted simulations to explore the temporal variations of ΔDIC-ΔDO regression slope with time. Comparing slopes derived from simulation and mixing model suggested that the biological signal of the decoupled waters likely preceded our observations by 6-10 days. Satellite results captured high-Chl a waters southwest of the low-salinity patch a week before our observation, potentially transported northward by prevailing southwest wind. Given that oxygen and pH are frequently measured in aquatic environments, their combined assessment could be a valuable method for assessing temporal algal bloom dynamics.

Transcutaneous electrical acupoint stimulation for alleviating pain in patients with advanced pancreatic cancer.

INTRODUCTION: Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer-related deaths globally, with a five-year survival rate of only 5%. OBJECTIVES: Pancreatic ductal adenocarcinoma is often fatal because of the lack of specific early symptoms and effective early screening tools. Therefore, 80%-85% of patients are usually diagnosed in the advanced stages. This study aimed to investigate the analgesic effect of transcutaneous electrical acupoint stimulation in patients with advanced pancreatic cancer. METHODS: Eighty patients with advanced pancreatic cancer were recruited from the Integrative Medicine Department of our hospital between June 2017 and October 2018 and randomly divided into the experimental group ( n = 40) and the control group ( n = 40). The experimental group received transcutaneous electrical acupoint stimulation combined with analgesic medication for 3 consecutive days, while the control group received only analgesic medication. The pain scores of the two groups before and after intervention were compared. RESULTS: The mean pain severity score was significantly lower in the experimental group than in the control group on day 1 ( P < 0.001), day 2 ( P < 0.001), day 3 ( P = 0.005), and day 4 ( P = 0.043). CONCLUSION: Transcutaneous electrical acupoint stimulation therapy effectively alleviates the pain of patients with advanced pancreatic cancer with a high degree of safety and minimal adverse effects, and is worthy of clinical application.

Leveraging the Fragment Molecular Orbital and MM-GBSA Methods in Virtual Screening for the Discovery of Novel Non-Covalent Inhibitors Targeting the TEAD Lipid Binding Pocket.

The Hippo pathway controls organ size and homeostasis and is linked to numerous diseases, including cancer. The transcriptional enhanced associate domain (TEAD) family of transcription factors acts as a receptor for downstream effectors, namely yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), which binds to various transcription factors and is essential for stimulated gene transcription. YAP/TAZ-TEAD facilitates the upregulation of multiple genes involved in evolutionary cell proliferation and survival. TEAD1-4 overexpression has been observed in different cancers in various tissues, making TEAD an attractive target for drug development. The central drug-accessible pocket of TEAD is crucial because it undergoes a post-translational modification called auto-palmitoylation. Crystal structures of the C-terminal TEAD complex with small molecules are available in the Protein Data Bank, aiding structure-based drug design. In this study, we utilized the fragment molecular orbital (FMO) method, molecular dynamics (MD) simulations, shape-based screening, and molecular mechanics-generalized Born surface area (MM-GBSA) calculations for virtual screening, and we identified a novel non-covalent inhibitor-BC-001-with IC50 = 3.7 µM in a reporter assay. Subsequently, we optimized several analogs of BC-001 and found that the optimized compound BC-011 exhibited an IC50 of 72.43 nM. These findings can be used to design effective TEAD modulators with anticancer therapeutic implications.

Elemental geochemical evidence for the river-derived sources of trace metals in surface sediments from Hangzhou Bay, East China Sea.

Coastal estuaries are often heavily subject to riverine influences by the inputs of sediment from terrestrial sources. Hangzhou Bay (HZB) is threatened by the riverine derived trace metals from two large rivers of Qiantang River (QTR) and Yangtze River (YZR). However, previous studies mainly focused on the incidental transport from the largest river in China (YZR) and failed to simultaneously evaluate the contributions of these two rivers, especially the directly flowing river of QTR, by their trace elemental geochemical composition and distribution. Herein, a comprehensive study identified the river-derived sources of multiple trace metals in surface sediments which transported from both of the rivers. The sampling stations were separated into three regions of YZR, HZB, and QTR based on their spatial distributions of sediment grain size and components. The significant variations for most of the trace metals concentrations, except for Cd, Th, and U, were found among three regions (χ2 ≥ 8.22, p ≤ 0.016). The highest concentrations in HZB were mainly resulted from the grain size effect (68.82% of the total variance), while the highest concentrations of Sr, Cd, and Ba in YZR and Zr and Hf in QTR were attributed to the anthropogenic source (11.90%) and mineral composition (6.21%) of river basins. After normalized the diversity of multiple trace metals concentrations and the influence of grain size by ratios of Igeo and EFLi, three regions were effectively distinguished. It was indicated that As, Cd, and Sb were enriched in the sediments of rivers by anthropogenic source (EFLi > 1.5 and/or Igeo > 1). The results evidenced that, after removing the influence of grain size, elemental geochemical composition of the surface sediments confidently identified the river-derived anthropogenic sources of the enriched trace metals from two major rivers, and largely from YZR.

Factors influencing the length of stay (LOS) undergoing robot-assisted thoracoscopic lung surgery in the setting of enhanced recovery after surgery (ERAS) protocol for pediatric patients: a retrospective study.

Background: A prolonged length of stay (LOS) after surgery may result in higher hospital costs and hospital-acquired complications. This study aims to identify the risk factors associated with a prolonged hospital stay after robot-assisted thoracoscopic lung surgery for pediatric patients in the context of enhanced recovery after surgery. Methods: The data for this retrospective study were collected from pediatric patients undergoing robot-assisted thoracoscopic lung surgery. Patients were divided into two subgroups based on median postoperative LOS (Group I: LOS > median 5 days and Group II: LOS ≤ median 5 days). Logistic regression analysis was used to identify the potential factors associated with increased LOS. Results: This study included 241 patients, 71 (29.46%) with an LOS of >5 days. The proportion of older children was significantly higher in Group I than that in Group II (P=0.004). Patients in Group I were more likely to experience a longer duration of anesthesia and surgery (P<0.001). They also had significantly higher rates of pneumonia, pleural effusion, and liver function damage (P<0.05). Several factors were identified to be associated with an increased LOS after robot-assisted thoracoscopic lung surgery: age >6 years [odds ratio (OR) =3.214, 95% confidence interval (CI): 1.464-7.502, P=0.004], surgery duration >100 min (OR =2.138, 95% CI: 1.296-4.387, P=0.005), intra-albumin (OR =13.778, 95% CI: 1.470-129.116, P=0.022), and blood loss >5 mL (OR =2.184, 95% CI: 1.082-4.409, P=0.029). Conclusions: The results revealed that older age, longer surgery duration, use of intra-albumin, and more blood loss predict longer postoperative hospital stay in pediatric patients with congenital lung lesions after robot-assisted thoracoscopic lung surgery.

The effect of lentinan on dexamethasone-induced immunosuppression in mice.

The immune system acts as a vital defense barrier against pathogenic invasions, and its stable operation is crucial for maintaining body health. Nevertheless, various natural or artificial factors can compromise the body's immune function, leading to immunosuppression, which may interfere with the efficacy of vaccination and increase the susceptibility of the body to disease-causing pathogens. In an effort to ensure successful vaccinations and improve overall physical well-being, the search for appropriate immune regulators to enhance immunity is of paramount importance. Lentinan (LNT) has a significant role in immune regulation and vaccine adjuvants. In the present study, we constructed an immunosuppressive model using dexamethasone (DEX) and demonstrated that LNT could significantly improved antibody levels in immunosuppressive mice and stimulated T-lymphocyte proliferation and differentiation in intestinal Peyer's patches. LNT also increased the production of secretory immunoglobulin A (sIgA) in the duodenal fluid, the number of goblet cells, and the proportion of mucin area. Moreover, LNT modulated the intestinal microbiota and increased the production of short-chain fatty acids. Additionally, LNT promoted the proliferation, differentiation, and pro-inflammatory cytokines production of DEX-treated splenic T lymphocytes in vitro. Thus, the present study highlights the potential of LNT in reversing immunosuppression and avoiding the failure of vaccination.

Ecosystem dynamics and hypoxia control in the East China Sea: A bottom-up and top-down perspective.

Decades of overfishing have greatly altered the community structure in the East China Sea (ECS). The decrease of top predators in the food web has weakened the control exerted from higher trophic levels. As a result, the biomass of benthic crustaceans, representing the third trophic level, has increased. This has probably led to a restriction of the second trophic level, diminishing its ability to control primary producer biomass. Consequently, the ecological pyramid of trophic levels in the ECS has been altered, reducing the top-down control on the first trophic level. This has made algal blooms more susceptible to occur under nutrient loads, temperate temperatures, and light availability. The reduced abundance of the fourth trophic levels has caused a larger portion of primary productivity to sink directly to the benthic community, bypassing the food web. This influx of sinking organic matter has resulted in organic enrichment in the bottom waters, impacting the biomass and diversity of benthic organisms. Furthermore, it has intensified anthropogenic carbon storage in the sediment. Subsequently, intense decomposition processes occur, leading to the development of anoxia and even hypoxia. The seasonal hypoxia off the Changjiang Estuary can be attributed to the combined influence of top-down control and bottom-up control related to nutrient loading, and terrestrial inputs. In order to mitigate extreme hypoxia events, it is necessary to implement comprehensive fisheries policies that prioritize the maintenance of a healthy and functional ecosystem. This approach should go beyond relying solely on watershed management strategies to regulate riverine inputs. PLAIN LANGUAGE SUMMARY: Decades of overfishing changed the food web in the East China Sea and weaken the resistance of ecosystem to hypoxia. Commercial fishing on top predators decreases the fourth trophic level while relatively increases the third trophic represented by crab and shrimp, which enhances grazing on the zooplankton. The decrease of the second trophic level fails to control the biomass of phytoplankton, thus more primary productivities directly sink to the benthic community and cause organic enrichment. The elevated flux of organic matters to the bottom waters causes the thrive of the carbs and shrimps, as well as more remineralization processes and eventually low oxygen level. Unlike the bottom-up perspective of hypoxia mechanism off the Changjiang Estuary, which is from the nutrient load, phytoplankton bloom, quick sink, effective decomposition and eventually hypoxia, the top-down control focuses on the changes of ecosystem structure and thus derived hindered energy transfer, changed community structure, enhanced carbon sink, elevated remineralization and ultimately hypoxia. These two mechanisms combine with each other and control the seasonal hypoxia off the Changjiang Estuary and even other coastal regions around the world.

Melatonin alleviates ischemic stroke by inhibiting ferroptosis through the CYP1B1/ACSL4 pathway.

This study utilized middle cerebral artery occlusion (MCAO) mouse models and HT-22 cell oxygen and glucose deprivation/reoxygenation (OGD/R) models to investigate the therapeutic effects of melatonin on ischemic brain injury. In the experiments, MCAO mice were treated with 5 and 10 mg/kg doses of melatonin, and H-T22 cells underwent OGD/R treatment and were administered different concentrations of melatonin. The results showed that melatonin significantly reduced ischemic brain area, neural damage, cerebral edema, and neuronal apoptosis in MCAO mice. In the HT-22 cell model, melatonin also improved cell proliferation ability, reduced apoptosis, and ROS production. Further mechanistic studies found that melatonin exerts protective effects by inhibiting ferroptosis, an iron-dependent form of regulated cell death, through regulation of the ACSL4/CYP1B1 pathway. In MCAO mice, melatonin decreased lipid peroxidation, ROS production, and ACSL4 protein expression. Overexpression of CYP1B1 increased ACSL4 ubiquitination and degradation, thereby increasing cell tolerance to ferroptosis, reducing ACSL4 protein levels, and decreasing ROS production. CYP1B1 knockdown obtained opposite results. The CYP1B1 metabolite 20-HETE induces expression of the E3 ubiquitin ligase FBXO10 by activating PKC signaling, which promotes ACSL4 degradation. In the OGD/R cell model, inhibition of CYP1B1 expression reversed the therapeutic effects of melatonin. In summary, this study demonstrates that melatonin protects the brain from ischemic injury by inhibiting ferroptosis through regulation of the ACSL4/CYP1B1 pathway, providing evidence for new therapeutic targets for ischemic brain injury.

High expression of B7-H3 on monocyte/macrophages in tumor microenvironment promotes lung cancer progression by inhibiting apoptosis.

Monocyte/macrophages constitute a significant population of tumor-infiltrating immune cells and play a crucial role in tumor growth, invasion, and metastasis. B7-H3, has immune regulatory functions, however, it is unclear whether B7-H3 expressed on monocyte/macrophages plays a significance role in tumor progression. We found B7-H3 was high-expressed on monocyte/macrophages in tumor microenvironment compared with adjacent tissues in lung cancer, and its expression level was positively correlated with the number of monocyte/macrophages. Furthermore, the expression of B7-H3 was related to clinical stage and lymph node metastasis. Moreover, miR-29a-3p negatively regulated B7-H3, and the expression of B7-H3 on THP-1-derived macrophages was regulated by secreting exosomes containing miR-29a-3p. In addition, knockdown of B7-H3 promoted macrophage apoptosis under hypoxia. Mechanistically, B7-H3 enhanced the antiapoptotic ability of macrophage by up-regulating HIF-1ɑ via activating NF-κB. Taken together, these results imply that B7-H3 as a therapeutic target could hold promise for enhancing anti-tumor immune responses in individuals diagnosed with lung cancer.

Intrathecal drug-infusion system for treating pain in advanced cancer: New research in patient management.

Currently, the treatment of cancer pain in China mainly follows the three-step pain relief principles formulated by the World Health Organization. As research on subarachnoid drug diffusion has intensified, intrathecal drug delivery has been gradually applied in the treatment of diseases, and improved analgesia can be achieved via the continuous infusion of small doses of morphine-derived drugs. This method can not only effectively relieve pain and enhance quality of life but also significantly reduce the incidence of nausea, vomiting, constipation, and other adverse reactions caused by the long-term intensive use of drugs in patients with cancer pain. This study summarizes the development of the intrathecal drug-infusion system for treating cancer pain in patients with advanced cancer and describes the drugs used, the advantages in pain treatment, and key nursing factors before and after device placement to provide a basis for alleviating pain in patients with cancer.

Transformer-Based Molecular Generative Model for Antiviral Drug Design.

Since the Simplified Molecular Input Line Entry System (SMILES) is oriented to the atomic-level representation of molecules and is not friendly in terms of human readability and editable, however, IUPAC is the closest to natural language and is very friendly in terms of human-oriented readability and performing molecular editing, we can manipulate IUPAC to generate corresponding new molecules and produce programming-friendly molecular forms of SMILES. In addition, antiviral drug design, especially analogue-based drug design, is also more appropriate to edit and design directly from the functional group level of IUPAC than from the atomic level of SMILES, since designing analogues involves altering the R group only, which is closer to the knowledge-based molecular design of a chemist. Herein, we present a novel data-driven self-supervised pretraining generative model called "TransAntivirus" to make select-and-replace edits and convert organic molecules into the desired properties for design of antiviral candidate analogues. The results indicated that TransAntivirus is significantly superior to the control models in terms of novelty, validity, uniqueness, and diversity. TransAntivirus showed excellent performance in the design and optimization of nucleoside and non-nucleoside analogues by chemical space analysis and property prediction analysis. Furthermore, to validate the applicability of TransAntivirus in the design of antiviral drugs, we conducted two case studies on the design of nucleoside analogues and non-nucleoside analogues and screened four candidate lead compounds against anticoronavirus disease (COVID-19). Finally, we recommend this framework for accelerating antiviral drug discovery.

Anesthesia management experience for pediatric day-case PDA ligation under thoracoscopy assisted by a robot: a retrospective study.

BACKGROUND: To summarize the anesthesia management experience for pediatric day-case patent ductus arteriosus (PDA) ligation under robot-assisted thoracoscopy and explore the key points of anesthesia management for this procedure. METHODS: The clinical data of 72 pediatric patients who underwent robot-assisted thoracoscopic day-case PDA ligation at the Children's Hospital, Zhejiang University School of Medicine from April 2021 to February 2023 were retrospectively analyzed. 0.3% ropivacaine local infiltration combined with S-ketamine 0.2 mg/kg intravenous injection was used for postoperative analgesia The patient's basic information and intraoperative conditions were analyzed, which included gender, age, weight, surgery time, anesthesia time, extubation time, intraoperative blood loss, MAP before pneumothorax, PaCO2 before pneumothorax, etc. Postoperative conditions were also monitored, such as PACU stay time, agitation during the recovery period, pain, and the incidence of nausea and vomiting. After discharge, the recovery status was assessed. RESULTS: A total of 70 pediatric patients who met the criteria for day-case PDA ligation were included in this study. Before the occurrence of pneumothorax, the mean arterial pressure (MAP) of these 70 patients was 69.58 ± 12.52 mmHg, and during controlled hypotension, the MAP was 54.96 ± 11.23 mmHg. Before the occurrence of pneumothorax, the partial pressure of carbon dioxide (PaCO2) was 38.69 ± 3.38 mmHg, and during controlled hypotension, the PaCO2 was 51.42 ± 4.05 mmHg. Three cases experienced agitation during the recovery period, and four cases had mild pain, but there was no moderate or severe pain, nausea, or vomiting. Only 1 case of postoperative respiratory tract infection and 1 case of postoperative pneumothorax occurred. Within 30 days after discharge, the unplanned revisit rate, unplanned readmission rate, and surgical wound infection rate were all 0. The residual shunt rate detected by echocardiography was 0 after 1 month. CONCLUSIONS: The children under the robot-assisted thoracoscopic day case PDA surgeries in this study have limited trauma, little bleeding, and little postoperative pain, though still at a risk of respiratory infection and pneumothorax.

Copper Nanoparticles Confined in a Silica Nanochannel Film for the Electrochemical Detection of Nitrate Ions in Water Samples.

The nitrate ion (NO3-) is a typical pollutant in environmental samples, posing a threat to the aquatic ecosystem and human health. Therefore, rapid and accurate detection of NO3- is crucial for both the aquatic sciences and government regulations. Here we report the fabrication of an amino-functionalized, vertically ordered mesoporous silica film (NH2-VMSF) confining localized copper nanoparticles (CuNPs) for the electrochemical detection of NO3-. NH2-VMSF-carrying amino groups possess an ordered perpendicular nanochannel structure and ultrasmall nanopores, enabling the confined growth of CuNPs through the electrodeposition method. The resulting CuNPs/NH2-VMSF-modified indium tin oxide (ITO) electrode (CuNPs/NH2-VMSF/ITO) combines the electrocatalytic reduction ability of CuNPs and the electrostatic attraction capacity of NH2-VMSF towards NO3-. Thus, it is a rapid and sensitive electrochemical method for the determination of NO3- with a wide linear detection range of 5.0-1000 µM and a low detection limit of 2.3 µM. Direct electrochemical detection of NO3- in water samples (tap water, lake water, seawater, and rainwater) with acceptable recoveries ranging from 97.8% to 109% was performed, demonstrating that the proposed CuNPs/NH2-VMSF/ITO sensor has excellent reproducibility, regeneration, and anti-interference abilities.

Leveraging the Fragment Molecular Orbital Method to Explore the PLK1 Kinase Binding Site and Polo-Box Domain for Potent Small-Molecule Drug Design.

Polo-like kinase 1 (PLK1) plays a pivotal role in cell division regulation and emerges as a promising therapeutic target for cancer treatment. Consequently, the development of small-molecule inhibitors targeting PLK1 has become a focal point in contemporary research. The adenosine triphosphate (ATP)-binding site and the polo-box domain in PLK1 present crucial interaction sites for these inhibitors, aiming to disrupt the protein's function. However, designing potent and selective small-molecule inhibitors can be challenging, requiring a deep understanding of protein-ligand interaction mechanisms at these binding sites. In this context, our study leverages the fragment molecular orbital (FMO) method to explore these site-specific interactions in depth. Using the FMO approach, we used the FMO method to elucidate the molecular mechanisms of small-molecule drugs binding to these sites to design PLK1 inhibitors that are both potent and selective. Our investigation further entailed a comparative analysis of various PLK1 inhibitors, each characterized by distinct structural attributes, helping us gain a better understanding of the relationship between molecular structure and biological activity. The FMO method was particularly effective in identifying key binding features and predicting binding modes for small-molecule ligands. Our research also highlighted specific "hot spot" residues that played a critical role in the selective and robust binding of PLK1. These findings provide valuable insights that can be used to design new and effective PLK1 inhibitors, which can have significant implications for developing anticancer therapeutics.