Can IMERG QPE product capture the heavy rain on urban flood scale?

Urban areas are increasingly vulnerable to sudden flooding disasters caused by intense rainfall and high imperviousness degree, resulting in great economic losses and human casualties. Interactions between rainfall data and urban catchment characteristics highlight the urgent need of accurate and effective precipitation data to apply in reliable hydrological simulations. However, it remains a challenge to obtain accurate rainfall datasets on such small scales in urban areas. As satellite remote sensing is the only method that can achieve global observation, it is important to evaluate satellite precipitation products in their ability to accurately capture intense precipitation on urban flood scales. This study evaluates the performance of the latest version 06B (V06B) Integrated Multi-satellitE Retrievals for Global Precipitation Measurement (IMERG) in North China Plain, with using the Radar-Gauge merged precipitation estimates as reference data. First, it could be concluded that IMERG fails to accurately estimate precipitation in the whole study area, having the problem of overestimating light precipitation and underestimating heavy precipitation. Second, results show that IMERG has poor ability to capture heavy precipitation on small scales, with the percentage of Hit nearly 0 and the percentage of Miss higher than 40 % for all the precipitation cases. Third, with the expansion of heavy precipitation centers' coverage, the problem of IMERG not to detect heavy precipitation gets mitigated, with the percentage of Miss decreasing by 14 % (19 %). However, the ability to capture both spatial location and precipitation intensity is still not good, the percentage of Hit ranging from 0.05 % to 7 %, without obvious improvement. When IMERG is able to capture the center of strong precipitation, it also tends to overestimate the weak precipitation around the center of strong precipitation. Results of this study provide an improved understanding of how well the V06B IMERG products capture the heavy precipitation center at small scales in urban areas, which will be useful for both developers and users of IMERG.

Triphenyl phosphate induces cardiotoxicity through myocardial fibrosis mediated by apoptosis and mitophagy of cardiomyocyte in mice.

Triphenyl phosphate (TPHP) is an organophosphorus flame retardant, but its cardiac toxicity has not been adequately investigated. Therefore, in the current study, the effect of TPHP on the heart and the underlying mechanism involved was evaluated. C57BL/6 J mice were administered TPHP (0, 5, and 50 mg/kg/day) for 30 days. In addition, H9c2 cells were treated with three various concentrations (0, 50, and 150 µM) of TPHP, with and without the reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine or the mitochondrial fusion promoter M1. TPHP caused cardiac fibrosis and increased the levels of CK-MB and LDH in the serum. TPHP increased the levels of ROS, malondialdehyde (MDA), and decreased the level of superoxide dismutase (SOD) and Glutathione peroxidase (GSH-Px). Furthermore, TPHP caused mitochondrial damage, and induced fusion and fission disorders that contributed to mitophagy in both the heart of C57BL/6 J mice and H9c2 cells. Transcriptome analysis showed that TPHP induced up- or down-regulated expression of various genes in myocardial tissue and revealed enriched apoptosis pathways. It was also found that TPHP could remarkably increase the expression levels of Bax, cleaved Caspase-9, cleaved Caspase-3, and decreased Bcl-2, thereby causing apoptosis in H9c2 cells. Taken together, the results suggested that TPHP promoted mitophagy through mitochondria fusion dysfunction resulting from oxidative stress, leading to fibrosis by inducing myocardial apoptosis.

Ferritinophagy-mediated ferroptosis of spermatogonia is involved in busulfan-induced oligospermia in the mice.

Busulfan, a bifunctional alkylated chemotherapeutic agent, has male reproductive toxicity and induce oligospermia, which is associated with ferroptosis. However, the specific target cells of busulfan-induced oligospermia triggered by ferroptosis are largely elusive, and the detailed mechanisms also require further exploration. In the present study, busulfan (0.6, and 1.2 mM, 48 h) causes ferroptosis in GC-1 spg cells through inducing Fe2+, ROS and MDA accumulation and functional inhibition of Xc-GSH-GPX4 antioxidant system. After inhibition of ferroptosis by Fer-1 (1 µM, pretreatment for 2 h) or DFO (10 µM, pretreatment for 2 h) reverses busulfan-induced destructive effects in GC-1 spg cells. Furthermore, using RNA-seq and Western blotting, we found that busulfan promotes autophagy-dependent ferritin degradation, as reflected by enriching in autophagy, increased LC3 II, Beclin1 and NCOA4, as well as decreased P62 and ferritin heavy chain 1 (FTH1). Ultimately, GC-1 spg cells and Balb/c mice were treated with busulfan and/or 3-MA, the inhibitor of autophagy. The results displayed that inhibition of autophagy relieves busulfan-induced FTH1 degradation and then blocks the occurrence of ferroptosis in GC-1 spg cells and testicular spermatogonia, which subsequently alleviates busulfan-caused testicular damage and spermatogenesis disorders. In summary, these data collectively indicated that ferroptosis of spermatogonia is involved in busulfan-induced oligospermia and mediated by autophagy-dependent FTH1 degradation, identifying a new target for the therapy of busulfan-induced male infertility.

Parkin-mediated mitophagy protects against aluminum trichloride-induced hippocampal apoptosis in mice via the mtROS-NLRP3 pathway.

Aluminum is a neurotoxic food contaminant. Aluminum trichloride (AlCl3) causes hippocampal mitochondrial damage, leading to hippocampal injury. Damaged mitochondria can release mitochondrial reactive oxygen species (mtROS) and activate nucleotide-binding oligomerization domain-like receptor-containing 3 (NLRP3) inflammasomes and apoptosis. E3 ubiquitin ligase PARK2 (Parkin)-mediated mitophagy can attenuate mitochondrial damage. However, the role of mitophagy in AlCl3-induced mice hippocampal damage and its regulatory mechanism remain elusive. First, C57BL/6 N mice were treated with 0, 44.825, 89.65, and 179.3 mg/kg body weight AlCl3 drinking water for 90 d. Apoptosis, NLRP3-inflammasome activation and mitochondrial damage were increased in AlCl3-induced hippocampal damage. In addition, Parkin-mediated mitophagy peaked in the middle-dose group and was slightly attenuated in the high-dose group. Subsequently, we used wild-type and Parkin knockout (Parkin-/-) mice to investigate the AlCl3-induced hippocampal damage. The results showed that Parkin-/- inhibited mitophagy, and aggravated AlCl3-induced mitochondrial damage, NLRP3-inflammasome activation, apoptosis and hippocampal damage. Finally, we administered MitoQ (mtROS inhibitor) and MCC950 (NLRP3 inhibitor) to AlCl3-treated Parkin-/- mice to investigate the mechanism of Parkin-mediated mitophagy. The results showed that inhibition of mtROS and NLRP3 attenuated hippocampal NLRP3-inflammasome activation, apoptosis, and damage in AlCl3-treated Parkin-/- mice. These findings indicate that Parkin-mediated mitophagy protects against AlCl3-induced hippocampal apoptosis in mice via the mtROS-NLRP3 pathway.

Establishment and validation of nomograms for predicting survival of lung invasive adenocarcinoma based on the level of pathological differentiation: a SEER cohort-based analysis.

Background: The pathological differentiation of invasive adenocarcinoma (IAC) has been linked closely with epidemiological characteristics and clinical prognosis. However, the current models cannot accurately predict IAC outcomes and the role of pathological differentiation is confused. This study aimed to establish differentiation-specific nomograms to explore the effect of IAC pathological differentiation on overall survival (OS) and cancer-specific survival (CSS). Methods: The data of eligible IAC patients between 1975 and 2019 were collected from the Surveillance, Epidemiology, and End Results (SEER) database, and randomly divided in a ratio of 7:3 into a training cohort and a validation cohort. The associations between pathological differentiation and other clinical characteristics were evaluated using chi-squared test. The OS and CSS analyses were performed using the Kaplan-Meier estimator, and the log-rank test was used for nonparametric group comparisons. Multivariate survival analysis was performed using a Cox proportional hazards regression model. The discrimination, calibration, and clinical performance of nomograms were assessed by area under receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis (DCA). Results: A total of 4,418 IAC patients (1,001 high-differentiation, 1,866 moderate-differentiation, and 1,551 low-differentiation) were identified. Seven risk factors [age, sex, race, tumor-node-metastasis (TNM) stage, tumor size, marital status, and surgery] were screened to construct differentiation-specific nomograms. Subgroup analyses showed that disparate pathological differentiation played distinct roles in prognosis, especially in patients with older age, white race, and higher TNM stage. The AUC of nomograms for OS and CSS in the training cohort were 0.817 and 0.835, while in the validation cohort were 0.784 and 0.813. The calibration curves showed good conformity between the prediction of the nomograms and the actual observations. DCA results indicated that these nomogram models could be used as a supplement to the prediction of the TNM stage. Conclusions: Pathological differentiation should be considered as an independent risk factor for OS and CSS of IAC. Differentiation-specific nomogram models with good discrimination and calibration capacity were developed in the study to predict the OS and CSS in 1-, 3- and 5-year, which could be used predict prognosis and select appropriate treatment options.

Diagnostic Value of Chromosomal Microarray Analysis for Fetal Congenital Heart Defects with Different Cardiac Phenotypes and Extracardiac Abnormalities.

(1) Background: The objective of this study was to investigate the diagnostic value of chromosomal microarray analysis (CMA) for congenital heart defects (CHDs) with different cardiac phenotypes and extracardiac abnormalities (ECAs) and to explore the pathogenic genetic factors of CHDs. (2) Methods: We collected fetuses diagnosed with CHDs by echocardiography at our hospital from January 2012 to December 2021. We analyzed the CMA results of 427 fetuses with CHDs. We then categorized the CHD into different groups according to two dimensions: different cardiac phenotypes and whether it was combined with ECAs. The correlation between the numerical chromosomal abnormalities (NCAs) and copy number variations (CNVs) with CHDs was analyzed. Statistical analyses, including Chi-square tests and t-tests, were performed on the data using IBM SPSS and GraphPad Prism. (3) Results: In general, CHDs with ECAs increased the detection rate for CA, especially the conotruncal defects. CHD combined with the thoracic and abdominal walls and skeletal, thymic and multiple ECAs, were more likely to exhibit CA. Among the CHD phenotypes, VSD and AVSD were associated with NCA, while DORV may be associated with NCA. The cardiac phenotypes associated with pCNVs were IAA (type A and B), RAA, TAPVC, CoA and TOF. In addition, IAA, B, RAA, PS, CoA and TOF were also associated with 22q11.2DS. The length distribution of the CNV was not significantly different between each CHD phenotype. We detected twelve CNV syndromes, of which six syndromes may be related to CHDs. The pregnancy outcome in this study suggests that termination of pregnancy with fetal VSD and vascular abnormality is more dependent on genetic diagnosis, whereas the outcome in other phenotypes of CHDs may be associated with other additional factors. (4) Conclusions: CMA examination for CHDs is still necessary. We should identify the existence of fetal ECAs and specific cardiac phenotypes, which are helpful for genetic counseling and prenatal diagnosis.

Triphenyl phosphate induced apoptosis of mice testicular Leydig cells and TM3 cells through ROS-mediated mitochondrial fusion inhibition.

Triphenyl phosphate (TPHP) is a widely used organophosphate flame retardant and has biological toxicity. Previous studies showed TPHP can restrain testosterone biosynthesis in Leydig cells, while the underlying mechanisms remain unclear. In this study, C57BL/6J male mice were exposed to 0, 5, 50, and 200 mg/kg B.W. of TPHP for 30 d by oral, as well as TM3 cells were treated with 0, 50, 100, and 200 µM of TPHP for 24 h. Results showed that TPHP induced testes damage, including spermatogenesis disorders and testosterone synthesis inhibition. Meanwhile, TPHP can cause apoptosis in testicular Leydig cells and TM3 cells, as evidenced by the increased apoptosis rate and decreased Bcl-2/Bax ratio. Moreover, TPHP disrupted mitochondrial ultrastructure of testicular Leydig cells and TM3 cells, reduced healthy mitochondria content and depressed mitochondrial membrane potential of TM3 cells, as well as inhibited mitochondrial fusion proteins mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and optic atrophy 1 (Opa1) expression, without effect on mitochondrial fission proteins dynamin-related protein 1 (Drp1) and fission 1 (Fis1) in testicular tissue and/or TM3 cells. Then, the mitochondrial fusion promoter M1 was used to pre-treat TPHP-exposed TM3 cells to determine the roles of mitochondrial fusion inhibition in TPHP-induced Leydig cells apoptosis. The results showed M1 pretreatment alleviated the above changes and further mitigated TM3 cells apoptosis and testosterone levels decreased, indicating TPHP induced TM3 cells apoptosis by inhibited mitochondrial fusion. Intriguingly, the intervention experiment of N-acetylcysteine (NAC) showed that TPHP-induced mitochondrial fusion inhibition is ROS dependent, because inhibition of ROS overproduction alleviated mitochondrial fusion inhibition, and subsequently relieved TPHP-induced apoptosis in TM3 cells. In summary, above data revealed that apoptosis is a specific mechanism for TPHP-induced male reproductive toxicity, and that ROS-mediated mitochondrial fusion inhibition is responsible for Leydig cells apoptosis caused by TPHP.

Pediatric Outpatient Occupational Therapy: Transitioning From In-Person Services to Telehealth.

The COVID-19 pandemic necessitated rapid adoption of telehealth for outpatient pediatric occupational therapy practice. The dose of therapy may have varied across diagnostic and geographical groups despite efforts to ensure access for all patients. The objective of the study was to describe the visit length of outpatient pediatric occupational therapy practice for three diagnostic groups at one institution both during and prior to the COVID-19 pandemic. Retrospective review of electronic health records for two time periods using both practitioner-entered and telecommunications data. Data were analyzed using descriptive statistics and generalized linear mixed model. Prior to the pandemic, average treatment length did not vary by primary diagnosis. During the pandemic, average visit length varied by primary diagnosis, with feeding disorder (FD) visits significantly shorter than cerebral palsy (CP) and autism spectrum disorder (ASD) visits. During the pandemic, visit length was associated with rurality for the whole sample and for patients with ASD and CP, but not FD. Patients with FD may have been seen for shorter durations during telehealth visits. The technology gap may affect services for patients living in rural communities.

Optimal Contact Position of Subthalamic Nucleus Deep Brain Stimulation for Reducing Restless Legs Syndrome in Parkinson's Disease Patients: One-Year Follow-Up with 33 Patients.

Objectives: To determine the short- and medium-term therapeutic effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on restless legs syndrome (RLS) in patients with Parkinson's disease (PD) and to study the optimal position of activated contacts for RLS symptoms. Methods: We preoperatively and postoperatively assessed PD Patients with RLS undergoing STN-DBS. Additionally, we recorded the stimulation parameters that induced RLS or relieved RLS symptoms during a follow-up. Finally, we reconstructed the activated contacts' position that reduced or induced RLS symptoms. Results: 363 PD patients were enrolled. At the 1-year follow-up, we found that the IRLS sum significantly decreased in the RLS group (preoperative 18.758 ± 7.706, postoperative 8.121 ± 7.083, p < 0.05). The results of the CGI score, MOS sleep, and RLS QLQ all showed that the STN-DBS improved RLS symptoms after one year. Furthermore, the activated contacts that relieved RLS were mainly located in the central sensorimotor region of the STN. Activated contacts in the inferior sensorimotor part of the STN or in the substantia nigra might have induced RLS symptoms. Conclusions: STN-DBS improved RLS in patients with PD in one year, which reduced their sleep disorders and increased their quality of life. Furthermore, the central sensorimotor region part of the STN is the optimal stimulation site.

Distinguish between Stochastic and Chaotic Signals by a Local Structure-Based Entropy.

As a measure of complexity, information entropy is frequently used to categorize time series, such as machinery failure diagnostics, biological signal identification, etc., and is thought of as a characteristic of dynamic systems. Many entropies, however, are ineffective for multivariate scenarios due to correlations. In this paper, we propose a local structure entropy (LSE) based on the idea of a recurrence network. Given certain tolerance and scales, LSE values can distinguish multivariate chaotic sequences between stochastic signals. Three financial market indices are used to evaluate the proposed LSE. The results show that the LSEFSTE100 and LSES&P500 are higher than LSESZI, which indicates that the European and American stock markets are more sophisticated than the Chinese stock market. Additionally, using decision trees as the classifiers, LSE is employed to detect bearing faults. LSE performs higher on recognition accuracy when compared to permutation entropy.

Long non-coding RNA ncRuPAR regulates gastric cancer cell proliferation and apoptosis via phosphoinositide 3-kinase/protein kinase B signaling.

Objective: To determine the effect and mechanism of the long non-coding RNA (lncRNA) ncRuPAR (non-protein coding RNA, upstream of coagulation factor II thrombin receptor [F2R]/protease-activated receptor-1 [PAR-1]) in human gastric cancer. Methods: HGC-27-ncRuPAR overexpression and MGC-803-ncRuPAR-RNAi knockdown gastric cancer cell lines were established. We assessed the effect of ncRuPAR on cell proliferation, apoptosis, migration, and invasion using Cell Counting Kit 8, flow cytometry, scratch and transwell assays, respectively. Differentially expressed genes in HGC-27-ncRuPAR overexpression and HGC-27-empty vector cell lines were identified using Affymetrix GeneChip microarray analysis. Ingenuity Pathway Analysis (IPA) of the microarray results was subsequently conducted to identify ncRuPAR-enriched pathways, followed by validation using real time-quantitative PCR (RT-qPCR). As one of the top enriched pathways, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was further examined by western blotting to determine its role in ncRuPAR-mediated regulation of gastric cancer pathogenesis. Results: ncRuPAR inhibited human gastric cancer cell proliferation and induced G1/S phase arrest and apoptosis, but did not affect migration or invasion in vitro. Overexpression of ncRuPAR in vitro was found to inhibit its known target PAR-1, as well as PI3K/Akt signaling. The downstream targets of PI3K/Akt, cyclin D1 was downregulated, but there was no change in expression level of B-cell lymphoma 2 (Bcl-2). Conclusions: We showed that lncRNA-ncRuPAR could inhibit tumor cell proliferation and promote apoptosis of human gastric cancer cells, potentially by inhibiting PAR-1, PI3K/Akt signaling, and cyclin D1. The results suggest a potential role for lncRNAs as key regulatory hubs in GC progression.

Progress in research on the role of exosomal miRNAs in the diagnosis and treatment of cardiovascular diseases.

Cardiovascular diseases are the most common diseases threatening the health of the elderly, and the incidence and mortality rates associated with cardiovascular diseases remain high and are increasing gradually. Studies on the treatment and prevention of cardiovascular diseases are underway. Currently, several research groups are studying the role of exosomes and biomolecules incorporated by exosomes in the prevention, diagnosis, and treatment of clinical diseases, including cardiovascular diseases. Now, based on the results of published studies, this review discusses the characteristics, separation, extraction, and identification of exosomes, specifically the role of exosomal miRNAs in atherosclerosis, myocardial injury and infarction, heart failure, aortic dissection, myocardial fibrosis, ischemic reperfusion, atrial fibrillation, and other diseases. We believe that the observations noted in this article will aid in the prevention, diagnosis, and treatment of cardiovascular diseases.

Research on the True Triaxial Mechanical Properties of Concrete under the Coupling Action of High Temperature and Biaxial Unequal Lateral Pressure.

Based on engineering practice and practical needs, this paper takes ordinary concrete specimens as the research object, and adopts a high-temperature true triaxial loading test system to carry out high-temperature uniaxial and true triaxial static compression tests of concrete under high-temperature conditions. By comparing with normal temperature conditions, this paper analyzes the influence of the coupling effect of high-temperature and biaxial unequal lateral pressure on the static mechanical properties of concrete. By analyzing the experimental data, we reached a series of conclusions and carried out theoretical research on this basis. High temperatures can significantly affect the uniaxial static pressure strength characteristics, deformation characteristics, and failure mode of concrete. When the temperature exceeds 400 °C, the compressive strength decreases significantly, the peak strain increases sharply, and the plasticity of concrete is further enhanced. The coupling effect of high-temperature deterioration and lateral pressure strengthening makes the true triaxial mechanical properties of concrete change significantly; 0.6:0.2 and 400 °C are the turning points of side pressure ratio and temperature that affect the change law of the true triaxial mechanical properties of concrete, respectively. Based on the study of the high-temperature deterioration factor and lateral pressure strengthening factor, this paper further puts forward a concrete strength formula under the coupling action of high temperature and biaxial unequal lateral pressure. It was verified that the formula has a high accuracy.

Experimental study of impact mechanical and microstructural properties of modified carbon fiber reinforced concrete.

This paper investigated the preparation method and the dispersion behaviour of Modified Carbon Nanotube-fiber Reinforcements (MCNF), the change laws and the effect mechanisms of dynamic compressive strength of MCNF concretes. Electrophoresis method was used to prepare MCNF and its interfacial shear performance was tested by interfacial shear strength (IFSS) test. In addition, the dispersion behavior of MCNF in simulated concrete solution was verified by turbidity method. Split Hopkinson Pressure Bar (SHPB), Scanning Electron Microscope (SEM) and Mercury Intrusion Porosimetry (MIP) tests were carried on concrete samples with different volume fractions (0%, 0.1%, 0.2%, 0.3%, 0.4%) of MCNF. The results show that carbon nanotubes are easier to deposit to the negative electrode, and the higher the content of polycarboxylate superplasticizer, the more obvious the dispersity of MCNF in alkaline environment. The dynamic compressive strength of MCNF concrete was 14.0-35.5% higher than that of untreated concrete, and reached the maximum when the MCNF content was about 0.3%. The MCNF was wrapped in concrete matrix and promoted hydration reaction of interface between cement and MCNF from microscopic observation. The addition of MCNF could increase the porosity. The volume percentage of ≥ 100 nm pore decreased first and then increased. Reasons for the improvement strength of MCNF concrete is that the bridging effect is stronger with the increase of MCNF content (≤ 0.3%) and limited when the MCNF content is equal to 0.4%. MCNF concrete could be used in actual engineering with high requirements for dynamic load.

Modeling Flow Diverters Using a Porous Medium Approach: A Fast Alternative to Virtual Flow Diverter Deployment.

BACKGROUND: The Tubridge flow diverter (FD) (MicroPort Medical Co. Ltd., Shanghai, China) is a novel device aimed at reconstructing the parent artery and eliminating the aneurysm. Numerical simulations based on virtual FD deployment allow the assessment of the complex nature of aneurismal flow changes before the actual intervention but are demanding on computational resources. Here, we evaluate an alternative strategy of modeling FD effects for the Tubridge system using a porous medium. The goal of this study is to reduce demands on time and complexity of the simulation procedure for applications in clinical research. METHODS: Ten patient-specific aneurysm models were reconstructed from retrospectively collected diagnostic 3-dimensional digital subtraction angiographic images. Virtual FDs were deployed (SolidWorks, Dassault Systems, Concord, Massachusetts, USA; Meshmixer, Autodesk, San Rafael, California, USA) and corresponding porous medium patches were constructed at the ostium with a research computational fluid dynamics prototype (Siemens Healthineers, Forchheim, Germany). Hemodynamic conditions were simulated in 2 approaches. RESULTS: Hemodynamics inside the aneurysm based on these 2 approaches were compared. Both approaches yielded similar results. Mean wall shear stress and mean pressure of the aneurysmal wall correlated significantly (r = 0.8, r = 1.0, P < 0.05) as did mean velocity and mean pressure at a region inside the aneurysm, at the ostium and at a cross section containing the main vertex (for velocities r = 0.9; for pressures r = 1.0, P < 0.05). The use of porous medium patches reduced the preparation and simulation time together by approximately 50%. CONCLUSIONS: Using a porous medium approach yields comparable mean values for hemodynamic alterations compared to direct virtual FD simulations. Additionally, the porous medium approach greatly reduced the modeling complexity and computation time.

Endoplasmic reticulum stress promotes blood-testis barrier impairment in mice with busulfan-induced oligospermia through PERK-eIF2α signaling pathway.

Busulfan, a chemotherapeutic agent for cancer, has detrimental effects on germ cells and fertility, yet the specific mechanisms remain largely uncertain. The blood-testis barrier (BTB) maintains a suitable microenvironment for germ cells self-renewal and spermatogenesis by blocking the interference and damage of deleterious substances. Therefore, we hypothesized that BTB abnormalities might be involved in busulfan-induced oligospermia. To verify the hypothesis, thirty male Balb/c mice were randomly administered with busulfan (at a total dose of 40 mg/kg body weight) by intraperitoneal injection for 4 weeks to establish the model of oligospermia. The results displayed that busulfan caused testicular histopathological lesions and spermatogenesis disorder. Meanwhile, busulfan disrupted BTB integrity and lessened the expressions of BTB junction proteins, including Occludin, Claudin-11 and Connexin-43. Furthermore, busulfan activated the endoplasmic reticulum (ER) stress and PERK-eIF2α signaling pathway, reflected by the increased protein expressions of GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. Finally, to evaluate whether the ER stress is involved in busulfan-induced BTB destruction, the ER stress inhibitor 4-Phenylbutyric acid (4-PBA, 1 mM) was used to intervene in busulfan-exposed TM4 cells. The results displayed that inhibition of ER stress alleviated the reduction of BTB junction protein expressions induced by busulfan in TM4 cells. These data collectively indicated that busulfan-induced BTB impairment was mediated by triggering ER stress and activation of the PERK-eIF2α signaling pathway, thereby damaging the spermatogenesis, providing a new therapeutic target for male infertility induced by busulfan.

Inhibition of Heat Shock Protein 90 Attenuates the Damage of Blood-Brain Barrier Integrity in Traumatic Brain Injury Mouse Model.

Heat shock protein 90 (HSP90) is widely found in brain tissue. HSP90 inhibition has been proven to have neuroprotective effects on ischemic strokes. In order to study the role of HSP90 in traumatic brain injury (TBI), we carried out the present study. A novel inhibitor of the HSP90 protein, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DA), has been investigated for its function on the blood-brain barrier (BBB) damage after traumatic brain injury (TBI) in mouse models. These C57BL/6 mice were used as a TBI model and received 17-DA (0.1 mg/kg/d, intraperitoneally) until the experiment ended. To find out whether 17-DA may protect against TBI in vitro, bEnd.3 cells belonging to mouse brain microvascular endothelium were used. The HSP90 protein expressions were raised after TBI at the pericontusional area, especially at 3 d. Our study suggested that 17-DA-treated mice improved the recovery ability of neurological deficits and decreased brain edema, Evans blue extravasation, and the loss of tight junction proteins (TJPs) post-TBI. 17-DA significantly promoted cell proliferation and alleviated apoptosis by inhibiting the generation of intracellular reactive oxygen species (ROS) to downregulate cleaved caspase-3, matrix metallopeptidase- (MMP-) 2, MMP-9, and P-P65 in bEnd.3 cells after the injury. As a result, we assumed that the HSP90 protein was activated post-TBI, and inhibition of HSP90 protein reduced the disruption of BBB and improved the neurobehavioral scores in a mouse model of TBI through the action of 17-DA, which inhibited ROS generation and regulated MMP-2, MMP-9, NF-κB, and caspase-associated pathways. Thus, blocking HSP90 protein may be a potential therapeutic strategy for TBI.

Change in weight category among youth early in the COVID-19 pandemic.

Remote learning and shelter-in-place orders during the COVID-19 pandemic are associated with obesity risk factors such as decreased physical activity, altered routines and sleep schedules, increased screen time, and non-nutritious food choices. The objective of this brief report is to describe change in weight category 3-6 months after the onset of the pandemic in a cohort of 4509 low-income youth. Inclusion criteria were youth aged 2-17 years with weight and height measure in a large primary care network between 1 January and 30 March 2020 (Q1), designated as pre-COVID period; and 1 June-30 September 2020, (Q3), as early-COVID period. Change in weight category was assessed between Q1 and Q3. Adjusting for visit type and time lapse, logistic regression was conducted to examine the association between weight category change and age, sex, and race/ethnicity. The proportion of youth with overweight or obesity increased from 37.8% to 44.6%; and declined by 5.6% in the healthy weight category. Over the 3-6 month period, 23.1% of youth gained ≥5 kg, 4.3% gained ≥10 kg, and 17.8% increased their BMI by ≥2 units. Among underweight youth, 45.3% switched to the healthy weight category, with a median weight gain of 2.1 kg (interquartile range [IQR] = 2.1 kg). Median weight gain was highest among those youth with severe obesity (5.8 kg, IQR = 5.2 kg). Younger age (2-9 years), female and ethnic-minority youth were more likely to change to a higher/worse weight category. Significant weight gain occurred in the first 3-6 months of the pandemic among low-income youth, reflecting the short-term effects of the pandemic.

Early Diagnosis and Treatment of Nine Patients with Severe Multiple Injuries Accompanied by Traumatic Aortic Dissection during Emergency Treatment.

Objective: This study is aimed at investigating the early diagnosis and efficacy of emergency treatments of nine patients with severe multiple injuries accompanied by traumatic aortic dissection (TAD). Methods: Patients who sustained severe multiple injuries accompanied by TAD following a car accident (n = 6) and falls from a height (n = 3) were treated in the emergency department of our hospital from October 2017 to July 2021. Data of these patients, including seven men and two women (average age, 53 ± 15.2 years; range, 18-83 years) were analysed retrospectively. Upon hospital arrival, the multidisciplinary treatment (MDT) trauma team, composed of doctors and nurses, immediately performed resuscitation following the Green Channel Consultation and Treatment Process for Severe Multiple Injuries. Life-threatening injuries were managed urgently. Blood tests and blood preparation and bedside B-scan ultrasonography and CT were performed. Aortic computed tomography angiography (CTA) was conducted decisively in patients suspected of TAD so that endovascular graft exclusion (EVGE) with the aortic covered stent can be performed promptly, followed by emergency management, second-stage surgery, and intensive care according to the injury control strategy. Results: This study included nine patients suffering from severe multiple injuries accompanied by Stanford type B TAD, with injury severity scores ranging from 35 to 43 points. Six patients underwent EVGE while receiving emergency treatment, whereas two patients who also had intracranial haemorrhage underwent selective EVGE. One case of TAD missed in the emergency department was detected 13 days after hospitalisation; therefore, the patient promptly underwent EVGE. Emergency procedures performed included exploratory laparotomy and splenectomy (n = 2), thoracic closed drainage (n = 5), haemothoracotomy (n = 3), second-stage fracture surgery (n = 4), and tracheotomy (n = 1). Postinjury complications included haemorrhagic shock, coagulation disorders, hyoxaemia, pulmonary infection, renal insufficiency, and hypoproteinaemia; however, all patients recovered after intensive care treatment. Aortic CTA after EVGE revealed the disappearance of the dissection and the resorption of the intermural haematoma. However, varying degrees of stenosis or occlusion were observed in the left subclavian artery. Nine patients with severe multiple injuries were treated satisfactorily by the MDT, without fatalities, and all patients were discharged for rehabilitation. Conclusion: In this study, procedures including resuscitation, urgent aortic CTA for definitive diagnosis, prompt EVGE, emergency injury control surgery, second-stage definitive surgery, intensive care treatment, and rehabilitation were rationally performed by the emergency MDT trauma team. Overall, this continuous and seamless process is a key factor for the successful treatment of patients with severe multiple injuries accompanied by TAD.