Synergistic promotion of nitrogen vacancies and single atomic dopants on Pt/C3N4 for photocatalytic hydrogen evolution.

C3N4 is widely applied in the synthesis of single-atom catalysts. However, understanding on the active site and the reaction mechanism is not fully in consensus. Especially, bare studies have considered the coordination environment of the single-atomic dopant and the effect of nitrogen vacancy on C3N4. In this study, we found that the presence of nitrogen vacancies promotes the activation of water and reduces the activation energy barrier for hydrogen generation. The results show that a synergistic effect between single-atom Pt and nitrogen vacancies enables the catalyst to achieve a superior hydrogen production rate of 3,890 µmol/g/h, which is 16.8 times higher than that of pristine C3N4. Moreover, the catalyst is also applicable for photocatalytic hydrogen production from seawater without significantly decreased hydrogen production rate. This study paves the way for the rational design and optimization of next-generation photocatalysts for sustainable energy applications, particularly in solar-driven hydrogen production.

A near-infrared turn-on fluorescent probe for the detection of hydrogen sulfide in water samples and food spoilage.

Hydrogen sulfide (H2S) is a poisonous pollutant that endangers the environment, and H2S is also produced during food spoilage. Herein, we constructed a dicyanoisophorone-based near-infrared (NIR) fluorescent probe (DCID) to detect H2S. DCID exhibited significant turn-on fluorescence at 700 nm with a low limit of detection (LOD = 74 nM), large Stokes shift (220 nm), prominent selectivity, and response time (100 s) toward H2S. Importantly, the DCID probe had powerful applications in the detection of H2S in environmental samples and food spoilage. In addition, based on DCID-loaded test strips and combined a smartphone sensing platform, which provided a portable and convenient approach for the detection of H2S.

A review on the cultivation, bioactive compounds, health-promoting factors and clinical trials of medicinal mushrooms Taiwanofungus camphoratus, Inonotus obliquus and Tropicoporus linteus.

Medicinal mushrooms, such as Taiwanofungus camphoratus, Inonotus obliquus, and Tropicoporus linteus, have been used in traditional medicine for therapeutic purposes and promotion of overall health in China and many East Asian countries for centuries. Modern pharmacological studies have demonstrated the large amounts of bioactive constituents (such as polysaccharides, triterpenoids, and phenolic compounds) available in these medicinal mushrooms and their potential therapeutic properties. Due to the rising demand for the health-promoting medicinal mushrooms, various cultivation methods have been explored to combat over-harvesting of the fungi. Evidence of the robust pharmacological properties, including their anticancer, hypoglycemic, hypolipidemic, antioxidant, and antiviral activities, have been provided in various studies, where the health-benefiting properties of the medicinal fungi have been further proven through numerous clinical trials. In this review, the cultivation methods, available bioactive constituents, therapeutic properties, and potential uses of T. camphoratus, I. obliquus and T. linteus are explored.

Many-Body Function Corrected Neural Network with Atomic Attention (MBNN-att) for Molecular Property Prediction.

Recent years have seen a surge of machine learning (ML) in chemistry for predicting chemical properties, but a low-cost, general-purpose, and high-performance model, desirable to be accessible on central processing unit (CPU) devices, remains not available. For this purpose, here we introduce an atomic attention mechanism into many-body function corrected neural network (MBNN), namely, MBNN-att ML model, to predict both the extensive and intensive properties of molecules and materials. The MBNN-att uses explicit function descriptors as the inputs for the atom-based feed-forward neural network (NN). The output of the NN is designed to be a vector to implement the multihead self-attention mechanism. This vector is split into two parts: the atomic attention weight part and the many-body-function part. The final property is obtained by summing the products of each atomic attention weight and the corresponding many-body function. We show that MBNN-att performs well on all QM9 properties, i.e., errors on all properties, below chemical accuracy, and, in particular, achieves the top performance for the energy-related extensive properties. By systematically comparing with other explicit-function-type descriptor ML models and the graph representation ML models, we demonstrate that the many-body-function framework and atomic attention mechanism are key ingredients for the high performance and the good transferability of MBNN-att in molecular property prediction.

Ultrasonic-Assisted Extraction and Gastrointestinal Digestion Characteristics of Polysaccharides Extracted from Mallotus oblongfolius.

The polysaccharides were extracted from the leaves of Mallotus oblongifolius (MO) using an ultrasonic-assisted extraction method in this study. The main variables affecting the yield of polysaccharides extracted from Mallotus appallatus (MOPS) were identified and optimized while concurrently investigating its antioxidant capacity, hypoglycemic activity, and digestive properties. The results indicated that the optimal ultrasound-assisted extraction of MOPS involved an ultrasound power of 200 W, a liquid-to-solid ratio of 25:1 (mL:g), an extraction temperature of 75 °C, and an ultrasound time of 45 min, leading to an extraction yield of (7.36 ± 0.45)% (m/m). The MOPS extract exhibited significant scavenging activity against DPPH and ABTS radicals with IC50 values of (25.65 ± 0.53) µg/mL and (100.38 ± 0.38) µg/mL, respectively. Furthermore, it effectively inhibited the enzymatic activities of α-glucosidase and α-amylase with IC50 values of (2.27 ± 0.07) mg/mL and (0.57 ± 0.04) mg/mL, respectively. The content of MOPS remained relatively stable in the stomach and small intestine; however, their ability to scavenge DPPH radicals and ABTS radicals and exhibit reducing power was attenuated, and the inhibition of α-amylase and α-glucosidase activity was diminished. In conclusion, the ultrasonic extraction of MOPS showed feasibility and revealed antioxidant and hypoglycemic effects. However, the activities were significantly reduced after gastric and small intestinal digestion despite no significant change in the MOPS content.

Near-infrared fluorescent probe for detection of hydrogen sulfide in water samples and food spoilage.

Hydrogen sulfide (H2S) is a common toxic gas that threatens the quality and safety of environmental water and food. Herein, a new near-infrared fluorescent probe DTCM was synthesized and characterized by single crystal X-ray diffraction for sensing H2S. It exhibited a remarkable "turn-on" near-infrared (NIR) emission response at 665 nm with a remarkably massive Stokes shift of 175 nm, super-rapid detection ability (within 30 s), excellent photostability, high selectivity and sensitivity (limit of detection, LOD = 58 nM). Additionally, the probe was successfully utilized for the detection of H2S in environmental water samples. The DTCM-loaded test papers enabled convenient and real-time monitoring of H2S produced by food spoilage.

Functional roles of circular RNAs in lung injury.

Lung injury leads to respiratory dysfunction, low quality of life, and even life-threatening conditions. Circular RNAs (circRNAs) are endogenous RNAs produced by selective RNA splicing. Studies have reported their involvement in the progression of lung injury. Understanding the roles of circRNAs in lung injury may aid in elucidating the underlying mechanisms and provide new therapeutic targets. Thus, in this review, we aimed to summarize and discuss the characteristics and biological functions of circRNAs, and their roles in lung injury from existing research, to provide a theoretical basis for the use of circRNAs as a diagnostic and therapeutic target for lung injury.

Human herpesvirus-6 infection in a critically ill and immunocompetent patient: a case report.

BACKGROUND: Human herpesvirus-6 is a rare infection in an immunocompetent adult. In existing literature, there is a dearth of knowledge that mainly exists as case reports and case series. CASE PRESENTATION: In this case report, we described a 29-year-old female of Myanmarese descent patient from Myanmar who presented with altered mental status and non-specific respiratory and gastrointestinal symptoms. She was initially treated for pneumonia and discharged well. However, she re-presented to the hospital and was subsequently treated for severe central nervous system infection. Cerebrospinal fluid studies detected human herpesvirus-6 polymerase chain reaction with associated high serum human herpesvirus-6 concentration. This infection also triggered hemophagocytic lymphohistiocytosis. Treatment was initiated against both human herpesvirus-6 infection and hemophagocytic lymphohistiocytosis, and she responded to antiviral treatment and steroids, respectively. CONCLUSION: This case study highlights the need for prompt diagnosis and treatment of this severe disease and the dangerous complications. Additionally, the authors share insights on the diagnostic challenges faced in the treatment of this patient.

A Cross-Sectional and Longitudinal Integrated Study on Brain Functional Changes in a Neuropathic Pain Rat Model.

Human and animal imaging studies demonstrated that chronic pain profoundly alters the structure and the functionality of several brain regions and even causes mental dysfunctions such as depression and anxiety disorders. In this article, we conducted a multimodal study cross-sectionally and longitudinally, to evaluate how neuropathic pain affects the brain. Using the spared nerve injury (SNI) model which promotes long-lasting mechanical allodynia, results showed that neuropathic pain deeply modified the intrinsic organization of the brain functional network 2 weeks after injury. There are significant changes in the activity of the left thalamus (Th_L) and left olfactory bulb (OB_L) brain regions after SNI, as evidenced by both the blood oxygen level-dependent (BOLD) signal and c-Fos expression. Importantly, these changes were closely related to mechanical pain behavior of rats. However, it is worth noting that after morphine administration for analgesia, only the increased activity in the TH region is reversed, while the decreased activity in the OB region becomes more prominent. Functional connectivity (FC) and c-Fos correlation analysis further showed these two regions of interest (ROIs) exhibit different FC patterns with other brain regions. Our study comprehensively revealed the adaptive changes of brain neural networks induced by nerve injury in both cross-sectional and longitudinal dimensions and emphasized the abnormal activity and FC of Th_L and OB_L in the pathological condition. It provides reliable assistance in exploring the intricate mechanisms of diseases.

Efficacy and safety of cadonilimab in previously treated recurrent or metastatic nasopharyngeal carcinoma(COMPASSION-06): A phase II multicenter study.

OBJECTIVE: This study was designed to assess the efficacy and safety of cadonilimab monotherapy, a first-in-class, bi-specific PD-1/CTLA-4 antibody, in patients with previously treated recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). PATIENTS AND METHODS: This multicenter, open-label, single-arm, phase II clinical trial enrolled patients with R/M-NPC who had failed first-line platinum-based chemotherapy and second-line single agent or combined chemotherapy, and immunotherapy-naive. Patients received cadonilimab for 6 mg/kg once every 2 weeks (Q2W). The primary endpoint was objective response rate (ORR) in full analysis set (FAS) assessed by investigators according to RECIST v.1.1. The secondary endpoint included progression-free survival (PFS), overall survival (OS), duration of response (DoR), time to response (TTR) and safety. RESULTS: A total of 23 patients were assessed. The median time from first dose to data cutoff was 16.56 (range, 0.8-25.2) months. ORR was 26.1 % (95 %CI:10.2-48.4). The ORR were 44.4 % (95 %CI: 13.7-78.8) and 14.3 % (95 %CI:1.8-42.8) in patients with tumor PD-L1 expression ≥50 % and <50 %, respectively. ORR was achieved in 40.0 % (95 %CI:12.2-73.8) of patients with EBV-DNA level <4000 IU/ml (n = 10) and 15.4 % (95 %CI:1.9-45.4) of those with ≥4000 IU/ml. The median PFS was 3.71 months (95 %CI: 1.84-9.30). respectively. Median OS was not reached, and the 12-month OS rate was 79.7 % (95 % CI:54.5-91.9). Only two patients (8.3 %) experienced Grade ≥3 treatment-related adverse events (TRAEs) with hypothyroidism (30.4 %), rash (21.7 %) and pruritus (21.7 %) being the most prevalent TRAEs. CONCLUSION: Cadonilimab monotherapy demonstrated a promising efficacy and manageable toxicity in patients with previously treated R-M/NPC and provide an efficacious salvage treatment option.

Melatonin-loaded gelatin methacryloyl microspheres delay nucleus pulposus degeneration / 中国组织工程研究

BACKGROUND:Nucleus pulposus degeneration is an important pathological link of intervertebral disc degeneration.Melatonin has a protective effect on cells through anti-inflammatory and antioxidant pathways,but the effect of melatonin on the nucleus pulposus has been less studied.At present,the emergence of various biological scaffolders provides a new idea for the study of drug-material combinations.OBJECTIVE:To explore whether melatonin can improve the metabolic state of the nucleus pulposus by reducing oxidative stress damage as well as the effect of gelatin methacryloyl(GelMA)microspheres loaded with melatonin on intervertebral disc degeneration in vivo.METHODS:In vitro,melatonin was combined with GelMA solution,and GelMA hydrogel was prepared into microspheres by microfluidic technology to co-culture with nucleus pulposus cells.The cell proliferation activity was detected by cell counting kit-8 assay,the surface morphology of the microspheres was observed under scanning electron microscopy,and the rate of drug release was detected by ultraviolet spectrophotometer.Then,interleukin-1β was used to induce degeneration of the nucleus pulposus.After treatment,the expression levels of aggrecan,type Ⅱ collagen α1,matrix metalloproteinase 13 and a disintegrin and metalloproteinase with thrombospondin motifs-5(ADAMTS5)in the nucleus pulposus were detected by qRT-PCR.In vivo,nucleus pulposus degeneration was induced by puncture.Subsequently,GelMA and GelMA@MT microspheres were injected.After 6 weeks,the specimens were taken for tissue staining,and the changes in tissue morphology were observed under the microscope for histological analysis and scoring.RESULTS AND CONCLUSION:(1)When the GelMA and GelMA@MT microspheres were observed under electron scanning microscope,melatonin binding did not change the morphology and external appearance of the microspheres.Drug release experiments showed that the drug release reached about 80%after 40 days.(2)Cell counting kit-8 assay results showed that both GelMA and GelMA@MT microspheres had no obvious cytotoxicity and promoted the proliferation of nucleus pulposus cells.(3)qRT-PCR results revealed that GelMA@MT microspheres increased the expression of aggrecan and type Ⅰ collagen α1 in the interleukin 1β environment by 42.1%and 27.1%,respectively,and decreased the expression of matrix metalloproteinase 13 and ADAMTS5 by 70.7%and 109.3%,respectively.(4)The level of reactive oxygen species was significantly lower in the interleukin 1β+GelMA@MT group than in the interleukin 1β and interleukin 1β+GelMA groups.(5)Histological staining of the sections showed that melatonin-loaded GelMA microspheres significantly delayed disc degeneration in vivo.(6)These findings indicate that GelMA@MT microspheres made by combining melatonin with GelMA hydrogel have good cytocompatibility in vitro and significantly delay nucleus pulposus degeneration in vitro and in vivo.

In vitro evaluation of sustained release Kartogenin by gelatin methacryloyl microspheres for repairing nucleus pulposus degeneration / 中国组织工程研究

BACKGROUND:The imbalance of matrix synthesis and degradation is the main cause of nucleus pulposus degeneration.Small molecule drug Kartogenin(KGN)can restore the balance of matrix synthesis and degradation.Sustained release of KGN using an appropriate drug delivery system is essential for the long-term and effective treatment of KGN.OBJECTIVE:To prepare the injectable hydrogel microspheres by encapsulating KGN with gelatin methacryloyl(GelMA)by microfluidic technology and to investigate the biocompatibility and biological function of nucleus pulposus cells.METHODS:β-Cyclodextrins(β-CD)and KGN were mixed firstly and then mixed with 10%GelMA at a volume of 1:9.Injectable hydrogel microspheres GelMA@β-CD@KGN were prepared by microfluidic technology.The micromorphology of the microspheres was characterized using a scanning electron microscope.The drug release of hydrogel microspheres immersed in PBS within one month was measured.Nucleus pulposus cells were isolated from SD rats and passage 1 cells were cultured in three groups.In the control group,nucleus pulposus cells were cultured separately.In the other two groups,GelMA@β-CD microspheres and GelMA@β-CD@KGN microspheres were co-cultured with nucleus pulposus cells.Cell proliferation was detected by CCK-8 assay and cell survival was detected by live/dead cell staining.Cells were cultured by two complete media with and without interleukin-1β with two kinds of microspheres.mRNA expressions of matrix synthesis and decomposing proteins in nucleus pulposus cells were detected by RT-PCR.RESULTS AND CONCLUSION:(1)Under the scanning electron microscope,the GelMA@β-CD@KGN microspheres after lyophilization were regularly spherical,highly dispersed,uniform in size and full in shape.GelMA@β-CD@KGN microspheres sustained drug release in vitro,reaching 62%of the total drug release at 30 days.(2)Live/dead cell staining showed that GelMA@β-CD@KGN could maintain the activity of nucleus pulposus cells.CCK-8 assay showed that GelMA@β-CD@KGN could promote the proliferation of nucleus pulposus cells.(3)In the complete media with and without interleukin-1β,mRNA expression of aggrecan and type Ⅱ collagen was higher in the GelMA@β-CD@KGN microsphere group than that in the GelMA@β-CD microsphere group(P<0.05,P<0.01);mRNA expression of matrix metalloproteinase 13 and platelet reactive protein disintegrin metallopeptidase 5 was lower than that in the GelMA@β-CD microsphere group(P<0.01).(4)These findings indicate that GelMA@β-CD@KGN microspheres have good biocompatibility and sustained drug release ability.As a drug delivery system,it is a kind of biomaterial with broad application prospects.

Advances in research on mechanisms related to myocardial regeneration in neonatal murine / 中国比较医学杂志

Cardiovascular disease is a health hazard to humans and systolic heart failure due to myocardial infarction is a major cause of death.It was previously thought that myocardial cells of the adult mammalian heart possess a limited ability to proliferate and self-renew.However,it has been widely reported that mammals have the ability to regenerate the myocardium,which is restricted to early postnatal life,and that it is strong enough to repair damaged heart tissue.The discovery of myocardial regeneration in neonatal hearts has provided an ideal animal model to investigate the mechanisms that affect myocardial regeneration,and many mechanisms that reverse myocardial cell cycle arrest and promote myocardial regeneration have been revealed.In this article,we review the factors affecting gene expression for myocardial regeneration(e.g.,ncRNAs and transcription factors),myocardial regeneration-related signaling pathways,and the regulation of myocardial regeneration by non-myocardial cells(e.g.,extracellular matrix,immune response,and epicardium)to provide directions for achieving myocardial regeneration after myocardial injury in adult mammals.

Evaluation of Hierarchical Diagnosis and Treatment Effect and Influencing Factors of Beijing Medical Alliance / 中国医院管理

Objective To understand the status quo of hierarchical diagnosis and treatment effect of medical alliance in Beijing and explore the influencing factors.Methods The convenience sampling method was used to select 26 vertical medical alliances,and the weighted TOPSIS method was used in combination with the index system established in the previous study to evaluate the effect of hierarchical diagnosis and treatment.The factors influencing the effect of hierarchical diagnosis and treatment in medical alliances were summarized through interviews with insiders,and the rank sum test was used to explore the factors influencing the effect of hierarchical diagnosis and treatment in medical alliances.Results The medical alliance B,A2 and A3 ranked high,and the implementation effect was relatively good in the four dimensions of"primary care first consultation,dual-way referral,acute and slow treatment,and vertical linkage";The C2,A8 and F2 medical alliances ranked low,and the implementation effect in the dimensions of"dual-way referral","acute and slow treatment"and"vertical linkage"was significantly lower than that of other medical alliances.The analysis results showed that the differences in the support intensity and core hospital level of different medical alliances were statistically significant(P＜0.05),which affected the hierarchical diagnosis and treatment effect of medical alliances.Conclusion While strengthening the information construction and improving the initiative of grassroots and the signing rate of family doctors,it is necessary to improve the support of core hospitals to promote the sinking of resources.Core hospitals should optimize resource allocation according to local conditions and promote hierarchical diagnosis and treatment.

Investigation on the standardization of medication reconciliation service in national medical institutions / 中国药房

OBJECTIVE To provide a reference for the implementation and high-quality development of hospital medication reconciliation. METHODS A semi-structured questionnaire was designed to investigate the implementation of drug reconciliation services in medical institutions before and after the release of 5 standards such as Standard for Medication Reconciliation Services in Medical Institutions（“standards” for short，in 2021 and 2022）. Descriptive statistical analysis was conducted on the survey results. RESULTS After the promulgation of the standards， the medication reconciliation service rate of all types of medical institutions increased from 15.10% （434/2 874） in 2021 to 27.84%（363/1 304） in 2022. In 2022， in the 363 medical institutions providing drug reconciliation services， the median number of pharmacists involved in drug reconciliation was 6. The participation rate of pharmacists in standardized training for drug reconciliation services was 75.00%， among which the participation rate of third-class hospitals was higher， reaching 85.71%. The main stages covered by medication reconciliation services included patient admission， transfer between departments， and discharge. The main problems found in the service included repeated medication （252， 69.42%）， inappropriate usage and dosage （228， 62.81%）， drug interactions and adverse reactions （218， E-mail：cputianxin@163.com 60.06%）. Only 69 institutions （19.01%） had a separate electronic information recording system， while 48 institutions 58516003。E-mail：zhenjiancun@vip.163.com （13.22%） had established comprehensive quality management and evaluation improvement systems. In terms of value embodiment， 141 institutions （38.84%） did not provide any form of compensation to relevant pharmacists. “Closely linked to enhancing patient satisfaction and improving services” was the most significant experience influencing medication reconciliation work（192， 52.89%）， while “the shortage of talent which meet the relevant requirements” stands as the primary challenge faced by medical institutions at all levels（238， 65.56%）. CONCLUSIONS The release of the standards has effectively improved the development rate of medication reconciliation in national medical institutions. However， there is still room for improvement in various aspects， including the allocation of personnel for medication reconciliation services， service content， information management， and the construction of quality control and evaluation systems.

Temporal trends in neurosurgical volume and length of stay in a public healthcare system: A decade in review with a focus on the COVID-19 pandemic.

Background: Over the past decade, neurosurgical interventions have experienced changes in operative frequency and postoperative length of stay (LOS), with the recent COVID-19 pandemic significantly impacting these metrics. Evaluating these trends in a tertiary National Health Service center provides insights into the impact of surgical practices and health policy on LOS and is essential for optimizing healthcare management decisions. Methods: This was a single tertiary center retrospective case series analysis of neurosurgical procedures from 2012 to 2022. Factors including procedure type, admission urgency, and LOS were extracted from a prospectively maintained database. Six subspecialties were analyzed: Spine, Neuro-oncology, Skull base (SB), Functional, Cerebrospinal fluid (CSF), and Peripheral nerve (PN). Mann-Kendall temporal trend test and exploratory data analysis were performed. Results: 19,237 elective and day case operations were analyzed. Of the 6 sub-specialties, spine, neuro-oncology, SB, and CSF procedures all showed a significant trend toward decreasing frequency. A shift toward day case over elective procedures was evident, especially in spine (P < 0.001), SB (tau = 0.733, P = 0.0042), functional (tau = 0.156, P = 0.0016), and PN surgeries (P < 0.005). Over the last decade, decreasing LOS was observed for neuro-oncology (tau = -0.648, P = 0.0077), SB (tau = -0.382, P = 0.012), and functional operations, a trend which remained consistent during the COVID-19 pandemic (P = 0.01). Spine remained constant across the decade while PN demonstrated a trend toward increasing LOS. Conclusion: Most subspecialties demonstrate a decreasing LOS coupled with a shift toward day case procedures, potentially attributable to improvements in surgical techniques, less invasive approaches, and increased pressure on beds. Setting up extra dedicated day case theaters could help deal with the backlog of procedures, particularly with regard to the impact of COVID-19.

Bronchobiliary fistula caused after percutaneous transhepatic biliary drainage treatment: A case report.

RATIONALE: Percutaneous transhepatic biliary drainage (PTBD) plays a significant role especially in the diagnosis and decompression of bile duct obstruction. However, it is associated with complications such as hemobilia, occlusion of drainage, bile leakage, and even bronchobiliary fistula (BBF). PATIENT CONCERNS AND DIAGNOSES: We herein describe a patient with a complication of BBF caused by long-term indwelling PTBD catheters. She underwent multiple operations including bilioenteric anastomosis, hepatic left lateral lobectomy, and long-term PTBD treatment. Her symptoms were mainly cough, fever, and yellow sputum and her diagnosis was confirmed by sputum culture (bilirubin detection was positive). INTERVENTIONS AND OUTCOMES: The patient recovered uneventfully by minimally invasive treatment, was discharged after 1 week of hospitalization, and the drainage tube was removed 2 weeks later. During 2 years of follow-up, no recurrence of BBF was observed. LESSONS: Patients with long-term indwelling PTBD catheters for biliary tract obstruction may lead to BBF. The treatment plan of BBF is tailored to the patient's individualized characteristics. And minimally invasive treatments might be an effective alternate way for the treatment of BBF. The accurate diagnosis, precision treatment, and multidisciplinary team play important roles in the treatment of BBF.

The risk factors, antimicrobial resistance patterns, and outcomes associated with extended-spectrum ß-lactamases-Producing pathogens in pediatric urinary tract infection.

BACKGROUND: Extended-spectrum ß-lactamases-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis (ESBL-producing-EKP) are an increasingly common cause of childhood urinary tract infection (UTI) worldwide. Recognizing the risk factors and antimicrobial resistance patterns may guide new management in this population. METHODS: This is a retrospective cohort study of over 5 years in Taiwan (2017-2021). Inclusion criteria are hospitalized pediatric patients with the discharge diagnosis of UTI caused by E. coli, Klebsiella pneumoniae, or Proteus mirabilis. ESBL-producing-EKP and non-ESBL-producing-EKP UTI cases were reviewed for characteristics, urinary isolate antibiotics resistance, and clinical outcomes. RESULTS: The incidence rate of ESBL-producing-EKP UTI increased over the study period (Overall incidence rate: 14.1 %, 46/327 patients). Recent antibiotic therapy in ≤6 months (X2 = 11.83, p < 0.01) and a preterm gestational history (X2 = 8.11, p < 0.05) were associated with an increased risk. The proportion of patients with these two risk factors for ESBL acquisition were 37.5 % (X2 = 9.08, p < 0.05). The co-resistance rate of ESBL-producing-EKP to other antimicrobial agents was 63.0 % for gentamicin, 56.5 % for trimethoprim-sulfamethoxazole, 52.2 % for ciprofloxacin, 4.3 % for amikacin, and 2.2 % for imipenem. The generalized linear model analysis identified a significantly longer length of stay (ß: 2.85; 95 % confidence interval [CI]: 1.14-4.56; p < 0.01) and intensive care unit duration (ß: 5.86; 95 % CI: 1.59-10.12; p < 0.01) among patients with ESBL-producing-EKP UTI. CONCLUSION: Amikacin should be considered as an alternative antimicrobial choice beyond carbapenems for ESBL-producing-EKP UTI, especially in the context of carbapenem-resistant E. coli/Klebsiella pneumoniae (CRE/CRKP) emergence.

Porcine reproductive and respiratory syndrome virus upregulates SMPDL3B to promote viral replication by modulating lipid metabolism.

Porcine reproductive and respiratory syndrome virus (PRRSV) poses a severe threat to the health of pigs globally. Host factors play a critical role in PRRSV replication. Using PRRSV as a model for genome-scale CRISPR knockout (KO) screening, we identified a host factor critical to PRRSV infection: sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B). Our findings show that SMPDL3B restricted PRRSV attachment, entry, replication, and secretion and that its depletion significantly inhibited PRRSV proliferation, indicating that SMPDL3B plays a positive role in PRRSV replication. Our data also show that SMPDL3B deficiency resulted in an accumulation of intracellular lipid droplets (LDs). The expression level of key genes (ACC, SCD-1, and FASN) involved in lipogenesis was increased, whereas the fundamental lipolysis gene, ATGL, was inhibited when SMPDL3B was knocked down. Overall, our findings suggest that SMPDL3B deficiency can effectively inhibit viral infection through the modulation of lipid metabolism.

Abnormality of anxious behaviors and functional connectivity between the amygdala and the frontal lobe in maternally deprived monkeys.

OBJECTIVE: Anxious behaviors often occur in individuals who have experienced early adversity. Anxious behaviors can bring many hazards, such as social withdrawal, eating disorders, negative self-efficacy, self-injurious thoughts and behaviors, anxiety disorders, and even depression. Abnormal behavior are is closely related to changes in corresponding circuit functions in the brain. This study investigated the relationship between brain circuits and anxious behaviors in maternal-deprived rhesus monkey animal model, which mimic early adversity in human. METHODS: Twenty-five rhesus monkeys (Macaca mulatta) were grouped by two different rearing conditions: 11 normal control and mother-reared (MR) monkeys and 14 maternally deprived and peer-reared (MD) monkeys. After obtaining images of the brain areas with significant differences in maternal separation and normal control macaque function, the relationship between functional junction intensity and stereotypical behaviors was determined by correlation analysis. RESULTS: The correlation analysis revealed that stereotypical behaviors were negatively correlated with the coupling between the left lateral amygdala subregion and the left inferior frontal gyrus in both MD and MR macaques. CONCLUSION: This study suggests that early adversity-induced anxious behaviors are associated with changes in the strength of the amygdala-prefrontal connection. The normalization of the regions involved in the functional connection might reverse the behavioral abnormality. It provides a solid foundation for effective intervention in human early adversity. SIGNIFICANCE STATEMENT: This study suggests that early adversity-induced anxious behaviors are associated with changes in the strength of the amygdala-prefrontal connection. The higher the amygdala-prefrontal connection strength, the less stereotyped behaviors exhibited by monkeys experiencing early adversity. Thus, in the future, changing the strength of the amygdala-prefrontal connection may reverse the behavioral abnormalities of individuals who experience early adversity. This study provides a solid foundation for effective intervention in humans' early adversity.