Ibuprofen modulates macrophage polarization by downregulating poly (ADP-ribose) polymerase 1.

Ibuprofen, a non-steroidal drug, is well known for its anti-inflammatory activity. The effects of ibuprofen on the polarization of macrophages are still not clear. Herein, we used THP-1 monocyte-derived macrophages to find that ibuprofen has inhibitory effects on the polarization of both classically activated M1 macrophages and alternatively activated M2 macrophages by downregulating NF-κB and JAK/STAT signaling pathways. During M1 or M2 polarization, ibuprofen also downregulated the expression of poly (ADP-ribose) polymerase 1 (PARP1). Furthermore, knockdown of PARP1 by either small interfering RNA or PARP1 inhibitor PJ34 can exert inhibitory effects on the polarization of M1 and M2, and alter the immune response of macrophages to the infection of Mycobacterium tuberculosis H37Ra. The results demonstrate that PARP1 plays a regulatory role in the ibuprofen-modulated polarization of macrophage, revealing the interplay between the DNA repair response process and macrophage polarization.

ALKBH4 functions as a hypoxia-responsive tumor suppressor and inhibits metastasis and tumorigenesis.

PURPOSE: The human AlkB homolog (ALKBH) dioxygenase superfamily plays a crucial role in gene regulation and is implicated in cancer progression. Under hypoxic conditions, hypoxia-inducible factors (HIFs) dynamically regulate methylation by controlling various dioxygenases, thereby modulating gene expression. However, the role of hypoxia-responsive AlkB dioxygenase remains unclear. METHODS: The molecular events were examined using real-time PCR and Western blot analysis. Tumor cell aggressiveness was evaluated through migration, invasion, MTT, trypan blue exclusion, and colony formation assays. In vivo metastatic models and xenograft experiments were conducted to evaluate tumor progression. RESULTS: Here, we examined the expression of the ALKBH superfamily under hypoxic conditions and found that ALKBH4 expression was negatively regulated by hypoxia. Knockdown of ALKBH4 enhanced the epithelial-mesenchymal transition (EMT), cell migration, invasion, and growth in vitro. The silencing of ALKBH4 enhanced metastatic ability and tumor growth in vivo. Conversely, overexpression of ALLKBH4 reversed these observations. Furthermore, overexpression of ALKBH4 significantly reversed hypoxia/HIF-1α-induced EMT, cell migration, invasion, tumor metastasis, and tumorigenicity. Notably, high expression of ALKBH4 was associated with better outcomes in head and neck cancer and breast cancer patients. Enrichment analysis also revealed that ALKBH4 was negatively enriched in hypoxia-related pathways. Clinically, a negative correlation between ALKBH4 and HIF-1α protein expression has been observed in tissues from both head and neck cancers and breast cancers. CONCLUSION: These findings collectively suggest that ALKBH4 acts as a tumor suppressor and holds therapeutic potential for hypoxic tumors.

Optimizing modern surgical simulation through instructor feedback - insights from a retrospective observational study in a tertiary hospital.

BACKGROUND: Laparoscopic surgery is associated with a prolonged learning curve for emerging surgeons, and simulation-based training (SBT) has become increasingly prominent in this context due to stringent working time regulations and heightened concerns regarding patient safety. While SBT offers a safe and ethical learning environment, the accuracy of simulators in the context of evaluating surgical skills remains uncertain. This study aims to assess the precision of a laparoscopic simulator with regard to evaluating surgical performance and to identify the instructor's role in SBT. MATERIALS AND METHODS: This retrospective study focused on surgical residents in their 1st through 5th years at the Department of Surgery of Linkou Chang Gung Memorial Hospital. The residents participated in a specially designed SBT program using the LapSim laparoscopic simulator. Following the training session, each resident was required to perform a laparoscopic procedure and received individualized feedback from an instructor. Both simulator and instructor evaluated trainees' performance on the LapSim, focusing on identifying correlations between the simulator's metrics and traditional assessments. RESULTS: Senior residents (n = 15), who employed more complex laparoscopic procedures, exhibited more significant improvements after receiving instructor feedback than did junior residents (n = 17). Notably, a stronger correlation between the simulator and instructor assessments was observed in the junior group (junior Global Operative Assessment of Laparoscopic Skills (GOALS) adjusted R2 = 0.285, p = 0.016), while no such correlations were observed among the senior group. CONCLUSION: A well-designed, step-by-step SBT can be a valuable tool in laparoscopic surgical training. LapSim simulator has demonstrated its potential in assessing surgical performances during the early stages of surgical training. However, instructors must provide intuitive feedback to ensure appropriate learning in later stages.

Use of Machine Learning to Predict Onset of NAFLD in an All-Comers Cohort-Development and Validation in 2 Large Asian Cohorts.

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. There are no universally accepted models that accurately predict time to onset of NAFLD. Machine learning (ML) models may allow prediction of such time-to-event (ie, survival) outcomes. This study aims to develop and independently validate ML-derived models to allow personalized prediction of time to onset of NAFLD in individuals who have no NAFLD at baseline. Methods: The development dataset comprised 25,599 individuals from a South Korean NAFLD registry. A random 70:30 split divided it into training and internal validation sets. ML survival models (random survival forest, extra survival trees) were fitted, with time to NAFLD diagnosis in months as the target variable and routine anthropometric and laboratory parameters as predictors. The independent validation dataset comprised 16,173 individuals from a Chinese open dataset. Models were evaluated using the concordance index (c-index) and Brier score on both the internal and independent validation sets. Results: The datasets (development vs independent validation) had 1,331,107 vs 543,874 person months of follow-up, NAFLD incidence of 25.7% (6584 individuals) vs 14.4% (2322 individuals), and median time to NAFLD onset of 60 (interquartile range 38-75) vs 24 (interquartile range 13-37) months, respectively. The ML models achieved a good c-index of >0.7 in the validation cohort-random survival forest 0.751 (95% confidence interval 0.742-0.759), extra survival trees 0.752 (95% confidence interval 0.744-0.762). Conclusion: ML models can predict time-to-onset of NAFLD based on routine patient data. They can be used by clinicians to deliver personalized predictions to patients, which may facilitate patient counseling and clinical decision making on interval imaging timing.

Neonatal sex and maternal factors associated with small-for-gestational-age neonates: A nationwide population-based study.

Background and Aims: Small-for-gestational-age (SGA) newborns have a higher risk of morbidity and mortality. Recognizing the risk factors for SGA helps raise early awareness of the issue and provides valuable insights for both healthcare providers and pregnant women. We aimed to identify determinants of SGA using population-based databases in Taiwan. Methods: Data were retrieved from the National Health Insurance, Birth Reporting, and Maternal and Child Health databases for this nationwide case-control study. Live births between 20 and 44 weeks of gestation from 2005 to 2014 were enrolled and linked to their mothers to determine maternal conditions during pregnancy. For every SGA newborn, four controls matched by gestational age and birth year were randomly selected. Multivariable logistic regression was used to identify risk factors for SGA, with adjusted odds ratios (aORs) and 95% confidence intervals (CIs) accounting for potential confounders and interaction terms. Results: A total of 158,405 live SGA births were identified, with 623,584 controls randomly selected. Independent risk factors for SGA included maternal age <20 years (aOR 1.68, 95% CI 1.62, 1.75); female sex in newborns (aOR 1.28, 95% CI 1.27, 1.30); socioeconomic deprivation (aOR 1.29, 95% CI 1.21, 1.38); hypertension (aOR 1.6, 95% CI 1.52, 1.67); kidney disorders (aOR 1.29, 95% CI 1.16, 1.44); thyroid disorders (aOR 1.13, 95% CI 1.09, 1.17); systemic lupus erythematosus (aOR 2.59, 95% CI 2.33, 2.89); antiphospholipid syndrome (aOR 2.08, 95% CI 1.64, 2.64); gestational hypertension (aOR 1.69, 95% CI 1.61, 1.76); pre-eclampsia (aOR 3.12, 95% CI 3.01, 3.25); and antepartum hemorrhage (aOR 1.05, 95% CI 1.03, 1.07) after adjustment for other covariates. Conclusions: SGA was associated with younger maternal age, female newborns, underlying comorbidities, and obstetric conditions. Gestational hypertension and pre-eclampsia were significant risk factors affecting infants of both sexes and all age groups and could mask the effects of maternal age and infant sex.

The application of machine learning for identifying frailty in older patients during hospital admission.

BACKGROUND: Early identification of frail patients and early interventional treatment can minimize the frailty-related medical burden. This study investigated the use of machine learning (ML) to detect frailty in hospitalized older adults with acute illnesses. METHODS: We enrolled inpatients of the geriatric medicine ward at Taichung veterans general hospital between 2012 and 2022. We compared four ML models including logistic regression, random forest (RF), extreme gradient boosting, and support vector machine (SVM) for the prediction of frailty. The feature window as well as the prediction window was set as half a year before admission. Furthermore, Shapley additive explanation plots and partial dependence plots were used to identify Fried's frailty phenotype for interpreting the model across various levels including domain, feature, and individual aspects. RESULTS: We enrolled 3367 patients. Of these, 2843 were frail. We used 21 features to train the prediction model. Of the 4 tested algorithms, SVM yielded the highest AUROC, precision and F1-score (78.05%, 94.53% and 82.10%). Of the 21 features, age, gender, multimorbidity frailty index, triage, hemoglobin, neutrophil ratio, estimated glomerular filtration rate, blood urea nitrogen, and potassium were identified as more impactful due to their absolute values. CONCLUSIONS: Our results demonstrated that some easily accessed parameters from the hospital clinical data system can be used to predict frailty in older hospitalized patients using supervised ML methods.

Experimental Study for the Sorption and Diffusion of Supercritical Carbon Dioxide into Polyetherimide.

Supercritical carbon dioxide (SCCO2) is a non-toxic and environmentally friendly fluid and has been used in polymerization reactions, processing, foaming, and plasticizing of polymers. Exploring the behavior and data of SCCO2 sorption and dissolution in polymers provides essential information for polymer applications. This study investigated the sorption and diffusion of SCCO2 into polyetherimide (PEI). The sorption and desorption processes of SCCO2 in PEI samples were measured in the temperature range from 40 to 60 °C, the pressure range from 20 to 40 MPa, and the sorption time from 0.25 to 52 h. This study used the ex situ gravimetric method under different operating conditions and applied the Fickian diffusion model to determine the mass diffusivity of SCCO2 during sorption and desorption processes into and out of PEI. The equilibrium mass gain fraction of SCCO2 into PEI was reported from 9.0 wt% (at 60 °C and 20 MPa) to 12.8 wt% (at 40 °C and 40 MPa). The sorption amount increased with the increasing SCCO2 pressure and decreased with the increasing SCCO2 temperature. This study showed the crossover phenomenon of equilibrium mass gain fraction isotherms with respect to SCCO2 density. Changes in the sorption mechanism in PEI were observed when the SCCO2 density was at approximately 840 kg/m3. This study qualitatively performed FTIR analysis during the SCCO2 desorption process. A CO2 antisymmetric stretching mode was observed near a wavenumber of 2340 cm-1. A comparison of loss modulus measurements of pure and SCCO2-treated PEI specimens showed the shifting of loss maxima. This result showed that the plasticization of PEI was achieved through the sorption process of SCCO2.

Multi-dimensional signals coupling of simultaneous acquisition stripping current with laser-induced breakdown spectroscopy for accurate analysis of Cd(II) in coexisting Cu(II).

BACKGROUND: Despite significant advancements in detecting Cd(II) using nanomaterials-modified sensitive interfaces, most detection methods rely solely on a single electrochemical stripping current to indicate concentration. This approach often overlooks potential inaccuracies caused by interference from coexisting ions. Therefore, establishing multi-dimensional signals that accurately reflect Cd(II) concentration in solution is crucial. RESULTS: In this study, we developed a system integrating concentration, electrochemical stripping current, and laser-induced breakdown spectroscopy (LIBS) characteristic peak intensity through in-situ laser-induced breakdown spectroscopy and electrochemical integrated devices. By simultaneously acquiring multi-dimensional signals to dynamically track the electrochemical deposition and stripping processes, we observed that replacement reactions occur between Cu(II) and Cd(II) on the surface of Ru-doped MoS2 modified carbon paper electrodes (Ru-MoS2/CP). These reactions facilitate the oxidation of Cd(0) to Cd(II) during the stripping process, significantly increasing the currents of Cd(II). Remarkably, the ingenious design of the Ru-MoS2 sensitive interface allowed for the undisturbed deposition of Cu(II) and Cd(II) during the electrochemical deposition process. Consequently, our in-situ integrated device achieved accurate detection of Cd(II) in complex environments, boasting a detection sensitivity of 8606.5 counts µM⁻1. SIGNIFICANCE: By coupling multi-dimensional signals from stripping current and LIBS spectra, we revealed the interference process between Cu(II) and Cd(II), providing valuable insights for accurate electrochemical analysis of heavy metal ions in complex water environments.

Adipocyte maturation impacts daunorubicin disposition and metabolism.

INTRODUCTION: Acute lymphoblastic leukaemia (ALL) is the most common type of childhood leukaemia with effective chemotherapeutic treatment. However, obesity has been associated with higher ALL chemoresistance rates and lower event-free survival rates. The molecular mechanism of how obesity promotes chemotherapy resistance is not well delineated. OBJECTIVES: This study evaluated the effect of adipocyte maturation on sequestration and metabolism of chemotherapeutic drug daunorubicin (DNR). METHODS: Using targeted LC-MS/MS multi-analyte assay, DNR sequestration and metabolism were studied in human preadipocyte and adipocyte cell lines, where expressions of DNR-metabolizing enzymes aldo-keto reductases (AKR) and carbonyl reductases (CBR) were also evaluated. In addition, to identify the most DNR-metabolizing AKR/CBR isoforms, recombinant human AKR and CBR enzymes were subject to DNR metabolism. The results were further validated by AKR-, CBR-specific inhibitors. RESULTS: This report shows that adipocyte maturation upregulates expressions of AKR and CBR enzymes (by 4- to 60- folds, p < .05), which is positively associated with enhanced sequestration and metabolism of DNR in adipocytes compared to preadipocytes (by ~30%, p < .05). In particular, adipocyte maturation upregulates AKR1C3 and CBR1, which are the predominate metabolic enzyme isoforms responsible for DNR biotransformation to its metabolites. CONCLUSION: Fat is an expandable tissue that can sequester and detoxify DNR when stimulated by obesity, likely through the upregulation of DNR-metabolizing enzymes AKR1C3 and CBR1. Our data partially explains why obese ALL patients may be more likely to become chemoresistant towards DNR, and provides evidence for potential clinical investigation targeting obesity to reduce DNR chemoresistance.

Parvovirus B19 Infection Is Associated with the Formation of Neutrophil Extracellular Traps and Thrombosis: A Possible Linkage of the VP1 Unique Region.

Neutrophil extracellular traps (NETs) formation, namely NETosis, is implicated in antiphospholipid syndrome (APS)-related thrombosis in various autoimmune disorders such as systemic lupus erythematosus (SLE) and APS. Human parvovirus B19 (B19V) infection is closely associated with SLE and APS and causes various clinical manifestations such as blood disorders, joint pain, fever, pregnancy complications, and thrombosis. Additionally, B19V may trigger the production of autoantibodies, including those against nuclear and phospholipid components. Thus, exploring the connection between B19V, NETosis, and thrombosis is highly relevant. An in vitro NETosis model using differentiated HL-60 neutrophil-like cells (dHL-60) was employed to investigate the effect of B19V-VP1u IgG on NETs formation. A venous stenosis mouse model was used to test how B19V-VP1u IgG-mediated NETs affect thrombosis in vivo. The NETosis was observed in the dHL-60 cells treated with rabbit anti-B19V-VP1u IgG and was inhibited in the presence of either 8-Br-cAMP or CGS216800 but not GSK484. Significantly elevated reactive oxygen species (ROS), myeloperoxidase (MPO), and citrullinated histone (Cit-H3) levels were detected in the dHL60 treated with phorbol myristate acetate (PMA), human aPLs IgG and rabbit anti-B19V-VP1u IgG, respectively. Accordingly, a significantly larger thrombus was observed in a venous stenosis-induced thrombosis mouse model treated with PMA, human aPLs IgG, rabbit anti-B19V-VP1u IgG, and human anti-B19V-VP1u IgG, respectively, along with significantly increased amounts of Cit-H3-, MPO- and CRAMP-positive infiltrated neutrophils in the thrombin sections. This research highlights that anti-B19V-VP1u antibodies may enhance the formation of NETosis and thrombosis and implies that managing and treating B19V infection could lower the risk of thrombosis.

Pig-to-human kidney xenotransplants using genetically modified minipigs.

This study develops an observational model to assess kidney function recovery and xenogeneic immune responses in kidney xenotransplants, focusing on gene editing and immunosuppression. Two brain-dead patients undergo single kidney xenotransplantation, with kidneys donated by minipigs genetically modified to include triple-gene knockouts (GGTA1, ß4GalNT2, CMAH) and human gene transfers (hCD55 or hCD55/hTBM). Renal xenograft functions are fully restored; however, immunosuppression without CD40-CD154 pathway blockade is ineffective in preventing acute rejection by day 12. This rejection manifests as both T cell-mediated rejection and antibody-mediated rejection (AMR), confirmed by natural killer (NK) cell and macrophage infiltration in sequential xenograft biopsies. Despite donor pigs being pathogen free before transplantation, xenografts and recipient organs test positive for porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) by the end of the observation period, indicating reactivation and contributing to significant immunopathological changes. This study underscores the critical need for extended clinical observation and comprehensive evaluation using deceased human models to advance xenograft success.

The roles of rabies virus structural proteins in immune evasion and implications for vaccine development.

Rabies is a zoonotic infectious disease that targets the nervous system of human and animals and has about 100% fatality rate without treatment. Rabies virus is a bullet-like viral particle composed of five structural proteins, including nucleoprotein (N), phosphorylated protein (P), matrix protein (M), glycoprotein (G), and large subunit (L) of RNA-dependent RNA polymerase. These multifunctional viral proteins also play critical roles in the immune escape by inhibiting specific immune responses in the host, resulting in massive replication of the virus in the nervous system and abnormal behaviors of patients such as brain dysfunction and hydrophobia, which ultimately lead to the death of patients. Herein, the role of five structural proteins of rabies virus in the viral replication and immune escape and its implication for the development of vaccines were systemically reviewed, so as to shed light on the understanding of pathogenic mechanism of rabies virus.

Hematopoietic stem cell transplantation activity in China 2022-2023. The proportions of peripheral blood for stem cell source continue to grow: a report from the Chinese Blood and Marrow Transplantation Registry Group.

Over past two years, a total of 39,918 hematopoietic stem cell transplantation (HSCT) cases were reported, with 18,194 and 21,714 transplants performed in 2022 and 2023, respectively. Autologous HSCT accounted for 6562 cases (31%) in 2022, while allogeneic HSCT comprised 12,632 cases (69%). In 2023, the number of allogeneic HSCTs exceeded 15,000, maintaining a 69% share. Participation in the 2022 and 2023 surveys included 193 and 212 transplantation teams, respectively, from 27 provinces, municipalities, or autonomous regions. The leading indication of HSCT was acute leukemia, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and mixed phenotype acute leukemia, with a total of 17,421 cases. AML was the most common disease (10,339, 38%) for allogeneic HSCT, which was followed by ALL (5925 cases, 21%). Peripheral blood emerged as the primary source of stem cell grafts, utilized in 54% of matched sibling donor transplants and 77% of haploidentical donor transplants. The BuCy-based conditioning regimen was the most prevalent, used in 53% of allogeneic HSCT cases in the past two years. This survey offers a comprehensive overview of the current HSCT landscape and serves as a valuable resource for clinical practice.

The dorsal raphe-to-ventral hippocampal projection modulates reactive aggression through 5-HT1B receptors.

Maladaptive reactive aggression is a core symptom of neuropsychiatric disorders such as schizophrenia. While uncontrolled aggression dampens societal safety, there is a limited understanding of the neural regulation involved in reactive aggression and its treatment. High levels of aggression have been linked to low serotonin (5-HT) levels. Additionally, post-weaning socially isolated (SI) mice exhibit outbursts of aggression following encountering acute stress, and hyperactivated ventral hippocampus (vHip) involves this stress-provoked escalated aggression. Here, we investigated the potential role of the raphe nucleus projecting to the vHip in modulating aggressive behavior. Chemogenetically activating the dorsal raphe nucleus (DRN) soma projecting the vHip or DRN nerve terminals in the vHip reduced reactive aggression. The reduction of attack behavior was abolished by the pretreatment of 5-HT1B receptor antagonist SB-224289. However, activating the median raphe nucleus (MRN)-to-vHip pathway ameliorated depression-like behavior but did not affect reactive aggression. DRN→vHip activation suppressed the vHip downstream area, the ventromedial hypothalamus (VMH), which is a core aggression area. Intra-vHip infusion of 5-HT1B receptor agonists (anpirtoline, CP-93129) suppressed reactive aggression and decreased c-Fos levels in the vHip neurons projecting to the VMH, suggesting an inhibition mechanism. Our findings indicate that activating the DRN projecting to the vHip is sufficient to inhibit reactive aggression in a 5-HT1B receptor-dependent manner. Thus, targeting 5-HT1B receptor could serve as a promising therapeutic approach to ameliorate symptoms of reactive aggression.

Application of Reducible Covalent Capture Purification for Resolving Persulfidome and Nucleolin S-Sulfhydration.

Protein S-sulfhydration involves the regulation of various protein functions, and resolving the S-sulfhydrated proteome (persulfidome) allows for a deeper exploration of various redox regulations. Therefore, we designed a reducible covalent capture method for isolating S-sulfhydrated proteins, which can analyze the persulfidome in biological samples and monitor specific S-sulfhydrated proteins. In this study, we applied this method to reveal the S-sulfhydration levels of proteins, including 3-phosphoglyceraldehyde dehydrogenase, NFκB/p65, and nucleolin. Furthermore, this technique can be used to enrich S-sulfhydrated peptides, aiding in the determination of protein S-sulfhydration modification sites. Finally, we observed that the S-sulfhydration and oxidation of nucleolin on the C543 residue correlate with its nuclear translocation, downstream regulation of p53, Bcl-xL, and Bcl-2 RNA levels and protein expression, as well as the protective function against oxidative stress. Therefore, this method may facilitate the understanding of the regulation of protein function by redox perturbation.

Manufacturing CD20/CD19-targeted iCasp9 regulatable CAR-TSCM cells using a Quantum pBac-based CAR-T engineering system.

CD19-targeted chimeric antigen receptor (CAR) T cell therapies have driven a paradigm shift in the treatment of relapsed/refractory B-cell malignancies. However, >50% of CD19-CAR-T-treated patients experience progressive disease mainly due to antigen escape and low persistence. Clinical prognosis is heavily influenced by CAR-T cell function and systemic cytokine toxicities. Furthermore, it remains a challenge to efficiently, cost-effectively, and consistently manufacture clinically relevant numbers of virally engineered CAR-T cells. Using a highly efficient piggyBac transposon-based vector, Quantum pBac™ (qPB), we developed a virus-free cell-engineering system for development and production of multiplex CAR-T therapies. Here, we demonstrate in vitro and in vivo that consistent, robust and functional CD20/CD19 dual-targeted CAR-T stem cell memory (CAR-TSCM) cells can be efficiently produced for clinical application using qPB™. In particular, we showed that qPB™-manufactured CAR-T cells from cancer patients expanded efficiently, rapidly eradicated tumors, and can be safely controlled via an iCasp9 suicide gene-inducing drug. Therefore, the simplicity of manufacturing multiplex CAR-T cells using the qPB™ system has the potential to improve efficacy and broaden the accessibility of CAR-T therapies.

The genetic diversity and evolution analysis of the Hainan melioidosis outbreak strains.

Melioidosis is a zoonotic disease, with its outbreaks being rare and indicative of an unusual concurrence of extreme climate and natural environmental factors. An outbreak of melioidosis cases emerged in Hainan following Typhoon "Dianmu" from October to December 2021, presenting an opportunity to identify the environmental sources of infection for these cases due to its nature as a well-defined point-source cluster. To investigate the relationship between the occurrence of these melioidosis cases and the environment, we extracted the entire genome of 25 clinical strains and conducted MLST typing, followed by whole genome sequencing and analysis of molecular genetic information for four ST46 genotypes from these strains. Phylogenetic and evolutionary relationships between Hainan sequence types (STs) and those found in other endemic regions were analyzed using IslandPath-DIMO, PHASTER, e-BURST, PHYLOViZ, and the maximum likelihood method. Notably, a total of 25 clinical strains were identified, encompassing 12 STs (ST46, ST1105, ST1991, ST30, ST1992, ST50, ST164, ST55, ST70, ST1993, ST1545, and ST58), with ST1991, ST1992, and ST1993 being newly discovered subtypes. PHYLOViZ clustering analysis divided the strains into two groups (A and B), both closely related to the Asian region. Phylogenetic tree analysis further revealed that most of the strains in this study were closely related to those found in Australia and Thailand. Analysis of patient information and visits to their residences suggested that contaminated water sources might be the primary source of infection during this outbreak. Our findings underscore that extreme weather events, such as typhoons, significantly increase the infection rate of B. pseudomallei, along with its genetic diversity, necessitating additional prevention strategies to control these B. pseudomallei infections.

Point mutation P174L of the penA gene endowing ceftazidime resistance to Burkholderia pseudomallei in China.

In a clinical isolate of Burkholderia pseudomallei from Hainan, the association between the emergence of ceftazidime resistance and a novel PenA P174L allele was identified for the first time, providing an understanding of one mechanism by which ceftazidime resistance arises in B. pseudomallei.

Associations between hollow viscus injury and acute kidney injury in blunt abdominal trauma: A national trauma data bank analysis.

PURPOSE: It is well established that hollow viscus perforation leads to sepsis and acute kidney injury (AKI) in non-trauma patients. However, the relationship between traumatic hollow viscus injury (HVI) and AKI is not well understood. Utilizing data from the National Trauma Data Bank, we investigated whether HVI serves as a risk factor for AKI. Additionally, we examined the characteristics of AKI in stable patients who underwent conservative treatment. METHODS: We reviewed blunt abdominal trauma (BAT) cases from 2012 to 2015, comparing patients with and without AKI. Significant factors from univariate analysis were tested in a multivariate logistic regression (MLR) to identify independent AKI determinants. We also analyzed subsets: patients without HVI and stable patients given conservative management. RESULTS: Out of the 563,040 BAT patients analyzed, 9073 (1.6%) developed AKI. While a greater proportion of AKI patients had HVI than those without AKI (13.3% vs. 5.2%, p < 0.001), this difference wasn't statistically significant in the MLR (p = 0.125). Notably, the need for laparotomy (odds = 3.108, p < 0.001) and sepsis (odds = 13.220, p < 0.001) were identified as independent risk factors for AKI. For BAT patients managed conservatively (systolic blood pressure >90 mmHg, without HVI or laparotomy; N = 497,066), the presence of sepsis was a significant predictor for the development of AKI (odds = 16.914, p < 0.001). CONCLUSIONS: While HVI wasn't a significant risk factor for AKI in BAT patients, the need for laparotomy was. Stable BAT patients managed conservatively are still at risk for AKI due to non-peritonitis related sepsis.

Supramolecular assemblies derived from methyl-substituted cucurbit[5]uril and lanthanide nitrates.

Interaction of the lanthanide nitrates M(NO3)3 (M = Gd, Eu) with methylcucurbit[5]uril (Me10Q[5]) in the presence of transition metal chlorides (ZnCl2 and FeCl3) in acidic media resulted in the isolation of the complexes [Me10Q[5]Gd(H2O)2Cl Gd(H2O)6](ZnCl4)2∙Cl∙8.9H2O (1) and [Me10Q[5]Eu(H2O)3Cl(H3O)](FeCl4)3 (2). The molecular structures of 1 and 2 have been determined by single crystal X-ray crystallography, and reveal discrete complexes which are involved in dense stacking with adjacent Me10Q[5]s linked via H-bonding and/or metal anions resulting in a supramolecular assembly.