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The abundance of specific hydrocarbon-oxidizing bacteria (MV value) in surface soil is closely linked to the concentration of thermogenic light hydrocarbons found in the underlying layers. The identification of these bacteria using specific detection techniques offers unique insights into microbiological anomalies associated with oil and gas, underscoring the significance of delineating microbiological geochemical anomalies in the exploration process. Accurate determination of the anomaly range is crucial for forecasting potential oil and gas reservoirs. In this study, a variety of fractal and geological statistical methods were employed to analyze microbiological geochemical data from the Taiwan Strait Basin. The multifractal approach allows for the simultaneous assessment of spatial autocorrelation and singularity in geochemical fields, with the fractal distribution reflecting the localized enrichment and depletion patterns of microbiological geochemical elements in rocks and other substrates. Geological statistical methods, such as the variation function, enable the assessment of spatial autocorrelation in geochemical and geophysical fields. The results indicate that microbiological anomalies in the Jiulongjiang Depression are mainly concentrated in the southwestern part of the study area, with some anomalies also observed in the central region. Conversely, microbiological anomalies in the Jinjiang Depression are predominantly located in the southern portion of the study area. Microbiological anomalies in the study area (Jinjiang Depression and Jiulongjiang Depression) exhibit a northeast-southwest strip distribution, aligning with the trend of the depressions and faults, suggesting that faults could influence the distribution of oil and gas resources in the region. Based on microbiological statistical analyses, the Jiulongjiang Depression shows better potential for oil and gas prospects compared to the Jinjiang Depression, guiding future research efforts in the Jiulongjiang Depression.

ObjectiveAn UPLC-MS/MS method was developed and validated for simultaneous determination of atracurium (ATC), dexmedetomidine (DEX), midazolam (MDZ) and 1-hydroxymidazolam (1-OH-MDZ) and the pharmacokinetics of ATC, DEX, MDZ and 1-OH-MDZ in patients undergoing aortic dissection surgery were investigated.MethodsThe analytes were extracted by acetonitrile precipitation and separated on an Acquity UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with a mobile phase of acetonitrile-0.1% formic acid and a gradient mode. In the positive ion mode, the following mass transition pairs were monitored by multiple reaction monitoring (MRM) for the four analytes and IS: m/z 385.1→206.2 for ATC, m/z 201.2→95.1 for DEX, m/z 326.1→291.1 for MDZ, m/z 341.9→324.0 for 1-OH-MDZ, and 284.9→153.9 for diazepam (IS). Seven male patients undergoing aortic dissection surgery received general anesthesia and intravenous administration of ATC, DEX, and MDZ during the surgery. Venous blood was collected at different time points at the end of surgery and after surgery. The concentrations of ATC, DEX, MDZ, and 1-OH-MDZ were detected, and the pharmacokinetic parameters were calculated.ResultsThe method showed good linearity for each analyte. The inter-batch precision ranged from 1.37% to 9.87% and the intra-batch precision ranged from 2.41% to 10.72%; the accuracy ranged from 94.33% to 104.51%. Finally, the matrix effect, extraction recovery and stability data met the FDA recommended acceptance criteria for validation of bioanalytical methods. The t1/2 of ATC, DEX, MDZ and 1-OH-MDZ was (6.74 ± 2.27) h, (9.55 ± 4.93) h, (10.17 ± 5.35) h, and (6.90 ± 2.38) h, the Cmax, of ATC, DEX, MDZ and 1-OH-MDZ was (1054.20 ± 202.37) ng/mL, (1.93 ± 1.07) ng/mL, (1256.57 ± 389.09) ng/mL, and (1034.39 ± 292.92) ng/mL in patients undergoing aortic dissection surgery, respectively.ConclusionThe developed UPLC-MS/MS method for simultaneous determination of ATC, DEX, MDZ and 1-OH-MDZ in patient plasma was accurate, reproducible, specific. After continuous administration of ATC, DEX, and MDZ to patients undergoing surgery for acute aortic dissection, the pharmacokinetics of ATC, DEX, MDZ and 1-OH-MDZ in patients undergoing aortic dissection surgery were studied.

Cell-free fetal DNA (cffDNA) screening is a valuable tool in clinical practice for detecting chromosomal abnormalities and autosomal dominant (AD) conditions. This study introduces a novel proof-of-concept assay designed for autosomal recessive (AR) cffDNA screening, focusing on cases involving the NPC1 gene. We aim to illustrate the significant benefits of AR cffDNA screening in managing high-risk pregnancies, specifically where biallelic pathogenic variants in NPC1 cause Niemann–Pick disease, type C1 (NPC), a disorder marked by progressive neurodegeneration. Three participants for this study were recruited and gave consent to a hospital in Saudi Arabia. These participants were either carriers of NPC or had a first- or second-degree relative affected by the disorder. No specific criteria were set for the age of the participants. All were between 15 and 18 weeks of gestation. Using amplicon-based next-generation sequencing (NGS), we analyzed the zygosity and variants in cffDNA extracted from maternal peripheral blood. After amplicon NGS, analysis was completed by a custom data analysis pipeline that included in-house-built data processing scripts and commonly used software packages. Importantly, the results were not disclosed to the patients. Our findings showed that in all three cases, AR cffDNA screening results were consistent with standard invasive diagnostic testing. This screening method offers several advantages: it provides critical information to families earlier in the pregnancy compared to invasive diagnostic tests, and it helps to alleviate parental anxiety. Moreover, this non-invasive method can determine pregnancy status in the first trimester for known familial variants. Future research may extend this approach to screen for known disease-causing variants in common AR conditions.

Background: Many factors can affect the clinical outcome of extremely premature infants (EPIs), but the effect of sex is paradoxical. This study used propensity score matching to adjust baseline information to reassess the clinical outcome of EPIs based on sex. Methods: A retrospective analysis was performed on EPIs admitted in the Department of Neonatology of the Third Affiliated Hospital of Guangzhou Medical University from 2011 to 2020. A propensity score matching (PSM) analysis was used to adjust the confounding factors including gestational age, birth weight, 1-minute Apgar score ≤ 3, withholding or withdrawing life-sustaining treatment(WWLST), mechanical ventilation, duration of mechanical ventilation, the mother with advanced age (≥35 years old), complete-course antenatal steroid therapy and hypertensive disorders of pregnancy. The survival rate at discharge and the incidence of major complications were evaluated between the male and female groups. Results: A total of 439 EPIs were included, and 240 (54.7%) infants were males. After matching the nine confounding factors, 148 pairs of infants were finally enrolled. There was no significant difference in the survival rate at discharge, as well as the mortality of activating treatment or WWLST between the two groups (all P >0.05). However, the incidence of respiratory distress syndrome, bronchopulmonary dysplasia (BPD), and moderate to severe BPD in the male group was significantly increased (all P <0.01), especially at birth weight between 750 and 999 grams. Conclusions: The male EPIs have a higher risk of respiratory complications than females, particularly at 750 to 999 grams of birth weight. [ABSTRACT FROM AUTHOR]

Corona Virus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has presented unprecedented challenges to the world. Changes after acute COVID-19 have had a significant impact on patients with neurodegenerative diseases. This study aims to explore the mechanism of neurodegenerative diseases by examining the main pathways of central nervous system infection of SARS-CoV-2. Research has indicated that chronic inflammation and abnormal immune response are the primary factors leading to neuronal damage and long-term consequences of COVID-19. In some COVID-19 patients, the concurrent inflammatory response leads to increased release of pro-inflammatory cytokines, which may significantly impact the prognosis. Molecular imaging can accurately assess the severity of neurodegenerative diseases in patients with COVID-19 after the acute phase. Furthermore, the use of FDG-PET is advocated to quantify the relationship between neuroinflammation and psychiatric and cognitive symptoms in patients who have recovered from COVID-19. Future development should focus on aggressive post-infection control of inflammation and the development of targeted therapies that target ACE2 receptors, ERK1/2, and Ca2+.

IntroductionAnti-PD-1/PD-L1 inhibitors therapy has become a promising treatment for hepatocellular carcinoma (HCC), while the therapeutic efficacy varies significantly among effects for individual patients are significant difference. Unfortunately, specific predictive biomarkers indicating the degree of benefit for patients and thus guiding the selection of suitable candidates for immune therapy remain elusive.no specific predictive biomarkers are available indicating the degree of benefit for patients and thus screening the preferred population suitable for the immune therapy. MethodsUltra-high-pressure liquid chromatography-mass spectrometry (UHPLC-MS) considered is an important method for analyzing biological samples, since it has the advantages of high rapid, high sensitivity, and high specificity. Ultra-high-pressure liquid chromatography-mass spectrometry (UHPLC-MS) has emerged as a pivotal method for analyzing biological samples due to its inherent advantages of rapidity, sensitivity, and specificity. In this study, potential metabolite biomarkers that can predict the therapeutic effect of HCC patients receiving immune therapy were identified by UHPLC-MS. ResultsA partial least-squares discriminant analysis (PLS-DA) model was established using 14 glycerophospholipid metabolites mentioned above, and good prediction parameters (R2 = 0.823, Q2 = 0.615, prediction accuracy = 0.880 and p < 0.001) were obtained. The relative abundance of glycerophospholipid metabolite ions is closely related to the survival benefit of HCC patients who received immune therapy. DiscussionThis study reveals that glycerophospholipid metabolites play a crucial role in predicting the efficacy of immune therapy for HCC.

Objective: To explore the difference in intestinal microecology between patients with preeclampsia and pregnant women at different stages of pregnancy.Methods: From January 2020 to January 2022, clinical data, including blood routine, lipid profile, and renal function indicators, were gathered from a cohort consisting of 5 cases of preeclampsia and 34 cases of non-preeclampsia. The non-preeclampsia group was further categorized into 6 cases in the First trimester, 13 cases in the Second trimester, and 15 cases in the Third trimester. The data collection took place at the Obstetrics Department of the Maternal and Child Health Hospital of Hubei Province. Additionally, fecal samples were obtained from each subject for 16S rDNA gene sequencing and subsequent analysis. The clinical data and composition characteristics of the gut microbiota in each group were analyzed, and the correlation between gut microbiota and clinical data was analyzed by the Spearman correlation analysis method.Results: In comparison to pregnant women without preeclampsia, preeclampsia patients exhibited a statistically significant elevation in blood routine parameters (WBC, N, L, and PLT count), a rise in lipid-related indicators (TC, TG, and LDL-C levels), a reduction in HDL-C levels, and an increase in renal function-related indicators (Cr, BUN, UA and Pro levels). Compared with non-preeclampsia pregnant women, preeclampsia women exhibited an augmented diversity of gut microbiota. Differences in gut microbiota composition between the two groups were observed at the gate and genus levels. Moreover, there are significant differences in the composition of gut microbiota between the preeclampsia group and the third-trimester group in terms of genus and species, and this difference is mainly caused by Prevotella and s_ Bacteroides_ Uniformis and Ruminococcus_ bromii. In addition, actinobacteria, bifidobacterium at the genus level, and Ruminococcus_bromii at the species level are positively correlated with clinically relevant indicators (excluding HDL-C).Conclusion: There are significant differences in gut microbiota between preeclampsia pregnant women and late pregnancy pregnant without preeclampsia, including Prevotella and Bacteroides_ Uniformis, and Ruminococcus_ bromii. In addition, these differential bacteria are correlated with most clinical indicators. However, additional comprehensive analysis is required to ascertain the functional correlation between these bacteria and clinical indicators.

Introduction: S100 calcium-binding protein A8 (S100A8) is also known as macrophage-related protein 8, which is involved in various pathological processes in the central nervous system post-traumatic brain injury (TBI), and plays a critical role in inducing inflammatory cytokines. Accumulating evidences have indicated that toll-like receptor 4 (TLR4) is considered to be involved in inflammatory responses post TBI. The present study was designed to analyze the hypothesis that S100A8 is the key molecule that induces inflammation via TLR4 in TBI. Methods: The weight-drop TBI model was used and randomly implemented on mice that were categorized into six groups: Sham, NS, S100A8, S100A8+TAK-242, TBI, and TBI+TAK-242 groups. In the S100A8+TAK-242 and TBI+TAK-242 groups, at half an hour prior to the intracerebroventricular administration of S100A8 or TBI, mice were intraperitoneally treated with TAK-242 that acts as a selective antagonist and inhibitor of TLR4. Furthermore, the protein recombinant of S100A8 was injected into the lateral ventricle of the brain of mice in the S100A8 and S100A8+TAK-242 groups. Sterile normal saline was injected into the lateral ventricle in the NS group. To evaluate the association between S100A8 and TLR4, Western blot, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and Nissl staining were employed. Simultaneously, the neurological score and brain water content were assessed. In the in vitro analysis, BV-2 microglial cells were stimulated with lipopolysaccharide LPS or S100A8 recombinant protein, with or without TAK-242. The expression of the related proteins was subsequently detected by Western blot or enzyme-linked immunosorbent assay. Results: The levels of S100A8 protein and pro-inflammatory cytokines were significantly elevated after TBI. There was a reduction in the neurological scores of non-TBI animals with remarkable severe brain edema after the intracerebroventricular administration of S100A8. Furthermore, the TLR4, p-p65, and myeloid differentiation factor 88 (MyD88) levels were elevated after the administration of S100A8 or TBI, which could be restored by TAK-242. Meanwhile, in the in vitro analysis, due to the stimulation of S100A8 or LPS, there was an upregulation of p-p65 and MyD88, which could also be suppressed by TAK-242. Conclusion: The present study demonstrated that the TLR4-MyD88 pathway was activated by S100A8, which is essential for the development of inflammation in the brain after TBI. [ABSTRACT FROM AUTHOR]

The crux of building and planning standards for age-friendly built environment in all countries resides in the regulation of age-friendly built environment practices, yet there exist variations in the representation of content dimensions. The UK is distinguished by its discretionary approach to guidance, whereas China exhibits a highly controlled disposition. Control and guidance may appear to be antithetical, it is essential to recognize that the building and planning standards for age-friendly built environment in both countries never deviate from the legal constraints while providing guidance in achieving age-friendly environments, thus striking a delicate balance between control and guidance. The study examines the standard systems of national standards, local standards and organizational standards, as well as the three dimensions of foundation standards, generic standards and specialized standards. The analysis of building and planning standards for age-friendly built environment in the UK and China scrutinizes the disparities between control and guidance, identifying similarities and differences in the building and planning standard system and content dimensions of the two countries. This analysis serves as a valuable reference for the development of building and planning standards for age-friendly built environment in China.

IntroductionTo explore the correlation between clinical and imaging features of malignant lung nodules and pathology types.MethodsPatients with lung nodules admitted to the Affiliated Hospital of Jiangsu University from January 1, 2020 to December 31, 2020 were collected as study subjects, and all of them underwent surgical treatment and were clearly diagnosed by pathology. The correlation between clinical and imaging features and pathological types of lung cancer patients was analyzed.ResultsAmong them, The pathological types of malignant pulmonary nodules are correlated with age, gender, smoking history, ground glass sign, nodule size, solid to solid ratio, lobulation sign, pleural indentation sign, hair prick sign, CEA, SCCA. The imaging features of ground glass sign and nodule size are most significantly correlated with the pathological type.ConclusionIt was found that, the clinical and imaging characteristics of patients with malignant lung nodules have a certain correlation with the pathological type, and gender, age, smoking history, nodule size, nodule nature, burr sign, pleural depression sign, and tumor markers are of great value for pathological typing.

For patients with locally recurrent rectal cancer (LRRC), the response rate to chemoradiotherapy is 40%–50%. Additionally, only approximately 40%–50% of patients with recurrent rectal cancer are able to undergo R0 resection. Recent studies in locally advanced rectal cancer (LARC) have shown promising synergistic effects when combining immunotherapy (PD-1/PD-L1 antibodies) with neoadjuvant chemoradiotherapy (nCRT). Therefore, incorporating immunotherapy into the treatment regimen for LRRC patients has the potential to further improve response rates and prognosis. To investigate this, the TORCH-R trial was conducted. This prospective, single-arm, two-cohort, phase II trial focuses on the use of hypofractionated radiotherapy, chemotherapy, and immunotherapy in LRRC patients without or with oligometastases. The trial will include two cohorts: cohort A consists of rectal cancer patients who are treatment-naive for local recurrence, and cohort B includes patients with progressive disease after first-line chemotherapy. Cohort A and cohort B patients will receive 25–40 Gy/5 Fx irradiation or 15–30 Gy/5 Fx reirradiation for pelvic recurrence, respectively. Subsequently, they will undergo 18 weeks of chemotherapy, toripalimab, and stereotactic ablative radiotherapy (SABR) for all metastatic lesions between chemoimmunotherapy cycles. Decisions regarding follow-up of complete response (CR), radical surgery, sustained treatment of non-resection, or exiting the trial are made by a multidisciplinary team (MDT). The primary endpoint of this study is the local objective response rate (ORR). The secondary endpoints include the extrapelvic response rate, duration of response, local recurrence R0 resection rate, progression-free survival (PFS), overall survival (OS), and safety and tolerability. Notably, this trial represents the first clinical exploration of inducing hypofractionated radiotherapy, chemotherapy, and immunotherapy in LRRC patients.Clinical trial registrationhttps://clinicaltrials.gov/study/NCT05628038, identifier NCT05628038.

Combination strategies to improve immunotherapy response in microsatellite stable metastatic colorectal cancer (MSS mCRC) remain an unmet need. Several single-arm clinical trials have shown promising synergistic effects between regorafenib and ICIs; however, some contradictory results have also been reported. Randomized controlled trials are needed to further validate the combination of regorafenib with ICIs. In addition, low-dose radiotherapy has been demonstrated to induce local immune responses by reprogramming the tumor microenvironment when combined with high-dose radiotherapy and ICIs. In this study, we designed a prospective, randomized, controlled phase II trial to investigate the efficacy and safety of regorafenib in combination with high/low-dose radiotherapy plus toripalimab in MSS mCRC compared to regorafenib alone. Patients with MSS metastatic adenocarcinoma of the colon or rectum will be enrolled and randomly assigned into two arms: a control arm and an experimental arm. Patients in the control arm will receive regorafenib monotherapy (120 mg once daily on days 1-21 of each 28 days cycle). Patients in the experimental arm will first receive one cycle of regorafenib (80 mg once daily on days 1-21 of each 28 days cycle) and toripalimab (240mg, q3w), followed by high-dose (4-8 fractions of 8-12Gy) and low-dose (1-10Gy at 0.5-2Gy/fraction) radiotherapy, and then continue regorafenib and toripalimab treatment. The primary endpoint is the objective response rate, and the secondary endpoints are disease control rate, duration of remission, median progress-free survival, median overall survival, and adverse events. Recruitment started in August 2023 and is ongoing.Clinical Trial Registrationhttps://clinicaltrials.gov/study/NCT05963490?cond=NCT05963490&rank=1, identifier NCT05963490.

Background: The role of body mass index (BMI) in the treatment outcomes of lymphoma patients is controversial. While investigating the efficacy of ABVD-like regimen in Hodgkin lymphoma (HL) patients, we observed that obese patients had poor responses. To better understand this clinical phenomenon, we evaluated the effect of BMI on responses to ABVD-like chemotherapy in HL patients.Methods: This retrospective cohort study evaluated the clinical outcomes of all 67 patients with confirmed HL who were treated at the First Affiliated Hospital of Soochow University from November 2016 to March 2023 with an ABVD-like regimen as first-line chemotherapy. Baseline patient characteristics and clinical outcomes were compared across different BMI categories. The primary end-point was the overall response rate defined as the proportion of the HL patients who achieved complete response or partial response. The additional end-points included progression-free survival and overall survival.Results: The median age of the HL patients was 31 years old. Of the patients, 10.4% were obese, and 17.9% patients were overweight. Interim and end-term response evaluations revealed overall response rates of 98.5% and 83.6%, respectively. The proportion of patients with potential poor prognostic factors (IPS risk factors) did not differ significantly in the responders versus non-responders. However, non-responders had a higher average BMI when compared with responders (p = 0.002). Poor overall response rates in higher BMI patients indeed manifested with shorter progression free survival (p = 0.013). The minimum relative dose of the ABVD-like regimen in the overweight and obese groups was significantly lower than in the normal weight group (p < 0.001).Conclusion: Our analyses show that >80% of newly-diagnosed HL patients responded to the ABVD-like regimen. We find that being obese or overweight at the time of diagnosis correlated with a poorer overall response rate and that BMI was an independent risk factor in HL patients treated with the ABVD-like regimen. Lower doses of ABVD-like regimen contributed to the discrepant findings of responses in the high BMI groups. These findings indicate that newly-diagnosed, obese HL patients receiving an ABVD-like regimen require personalized treatment.

The impedance of power lines is influenced by geological conditions and skin effect, resulting in frequency-dependent characteristics. In this study, a centralized parameter frequency-dependent line model based on first-order rational function fitting is investigated for short overhead transmission lines. The proposed model incorporates a parallel branch consisting of resistance and inductance obtained through rational function fitting, which mimics the frequency-dependent behavior of the line. The coupling between multiple conductors is represented using controlled sources. Comparative analysis of fitting accuracy and computational efficiency across various orders of rational functions reveals that the first-order rational function fitting offers superior computational efficiency while maintaining high accuracy in the medium and low-frequency range. Simulation results demonstrate that the proposed model, when disregarding wave propagation effects, exhibits comparable accuracy to the distributed parameter line model while achieving higher computational efficiency. Moreover, in transient analysis predominantly influenced by power frequency, the proposed model outperforms the frequency-independent pi(π) line model in terms of accuracy.

IntroductionThis study was performed to examine whether there is a link between the application of three types of robot-guided stereotactic biopsy techniques and the diagnostic rate of intracranial lesion biopsy.MethodsThe study involved 407 patients who underwent robot-guided stereotactic intracranial lesion biopsy at Xuanwu Hospital of Capital Medical University from January 2019 to December 2021. Age, sex, lesion characteristics, lesion distribution, surgical method, and target path depth were assessed for their impact on the biopsy diagnostic rate.ResultsThe patients’ mean age was 42.1 years (range, 6 months–82 years). All patients underwent robot-assisted stereotactic brain biopsy using one of three different systems: a ROSA robotic system (n=35), the CAS-R-2 (n=65), or the REMEBOT domestic robotic system (n=307). No significant difference was found in the diagnostic rate of positive histopathological findings or the mean time of surgery among the three biopsy modalities. The diagnostic rate was 93.86%. Multiple linear regression analysis showed that age, sex, and biopsy modality did not affect the diagnostic rate n>0.05), whereas enhancing lesions and smaller-volume lesions (≤l cm3) were significantly correlated with the diagnostic rate (p = 0.01). Lesions located in the suprasellar and pineal regions were significantly associated with the negative diagnostic rate (p

PurposeThe pain caused by spinal cord injury (SCI) poses a major burden on patients, and pain management is becoming a focus of treatment. Few reports have described changes in the brain after SCI. Particularly, the exact mechanism through which brain regions affect post-injury pain remains unclear. In this study, we aimed to determine the potential therapeutic mechanisms of pain. A mouse model of spinal cord contusion was established, and molecular expression in the anterior cingulate cortex (ACC) and periaqueductal gray (PAG) in the brain and animal behavior was observed after local injection of human umbilical cord mesenchymal stem cells (HU-MSCs) at the site of SCI.MethodSixty-three female C57BL/6J mice were divided into four groups: a sham operation group (n = 15); a spinal injury group (SCI, n = 16); an SCI + HU-MSCs group (n = 16) and an SCI + PBS group (n = 16), in which the SCI site was injected with HU-MSCs/phosphate buffer. The BMS score was determined, and the von Frey test and Hargreaves test were used to assess behavior every week after surgery. Mice were sacrificed in the fourth week after operation, and samples were collected. The expression of CGRP, Substance P, C-Fos and KCC2 in the ACC and PAG were observed with immunohistochemistry. Chromic cyanine staining was used to observe transverse sections of the injured spinal cord.ResultIn the ACC and PAG after SCI, the expression of CGRP, SP and C-Fos increased, and the expression of KCC2 decreased, whereas after HU-MSC injection, the expression of CGRP, SP and C-Fos decreased, and the expression of KCC2 increased. The SCI + HU-MSC group showed better exercise ability from 2 to 4 weeks after surgery than the SCI/SCI + PBS groups (P < 0.001). Local injection of HU-MSCs significantly improved the mechanical hyperalgesia caused by SCI in the fourth week after surgery (P < 0.0001), and sensation was significantly recovered 2 weeks after surgery (P < 0.0001); no improvement in thermal hypersensitivity was observed (P > 0.05). The HU-MSC group retained more white matter than the SCI/SCI + PBS groups (P < 0.0001).ConclusionLocal transplantation of HU-MSCs at the site of SCI partially relieves the neuropathic pain and promotes recovery of motor function. These findings suggest a feasible direction for the future treatment of SCI.

MicroRNAs (miRNAs) are small, noncoding RNAs that play a crucial role in the complex and dynamic network that regulates the apoptosis of porcine ovarian granulosa cells (POGCs). Resveratrol (RSV) is a nonflavonoid polyphenol compound that is involved in follicular development and ovulation. In previous study, we established a model of RSV treatment of POGCs, confirming the regulatory effect of RSV in POGCs. To investigate the miRNA-level effects of RSV on POGCs to reveal differentially expressed miRNAs, a control group (n = 3, 0 μM RSV group), a low RSV group (n = 3, 50 μM RSV group), and a high RSV group (n = 3, 100 μM RSV group) were created for small RNA-seq. In total, 113 differentially expressed miRNAs (DE-miRNAs) were identified, and a RT-qPCR analysis showed a correlation with the sequencing data. Functional annotation analysis revealed that DE-miRNAs in the LOW vs. CON group may be involved in cell development, proliferation, and apoptosis. In the HIGH vs. CON group, RSV functions were associated with metabolic processes and responses to stimuli, while the pathways were related to PI3K24, Akt, Wnt, and apoptosis. In addition, we constructed miRNA-mRNA networks related to Apoptosis and Metabolism. Then, ssc-miR-34a and ssc-miR-143-5p were selected as key miRNAs. In conclusion, this study provided an improved understanding of effects of RSV on POGCs apoptosis through the miRNA modulations. The results suggest that RSV may promote POGCs apoptosis by stimulating the miRNA expressions and provided a better understanding of the role of miRNAs combined with RSV in ovarian granulosa cell development in pigs.

BackgroundAssociations between non-optimal temperatures and cardiovascular disease (CVD) mortality risk have been previously reported, yet the trends of CVD mortality attributable to non-optimal temperatures remain unclear in China. We analyzed trends in CVD mortality attributable to non-optimal temperatures and associations with age, period, and birth cohort.MethodsData were obtained from the Global Burden of Disease Study (GBD) 2019. Joinpoint regression analysis was used to calculate annual percent change (APC) and average annual percent change (AAPC) from 1990 to 2019. We used the age-period-cohort model to analyze age, period, and cohort effects in CVD mortality attributable to non-optimal temperatures between 1990 and 2019.ResultsThe age-standardized mortality rate (ASMR) of CVD attributable to non-optimal temperature generally declined in China from 1990 to 2019, whereas ischemic heart disease (IHD) increased slightly. Low temperatures have a greater death burden than high temperatures, but the death burden from high temperatures showed steady increases. Joinpoint regression analysis showed that CVD mortality decreased in all age groups except for IHD, and the decreases were greater in females than in males. The mortality of CVD attributable to non-optimal temperatures of males was higher than females. The mortality rate showed an upwards trend with age across all CVD categories. Period risks were generally found in unfavorable trends. The cohort effects showed a progressive downward trend during the entire period.ConclusionAlthough there have been reductions in CVD mortality attributable to non-optimum temperatures, the mortality of IHD has increased and the burden from non-optimal temperatures remains high in China. In the context of global climate change, our results call for more attention and strategies to address climate change that protect human health from non-optimal temperatures.

Background and purposeThough hypertension disorders of pregnancy (HDP) are recognized as independent pregnancy-associated stroke risk factors, few studies have considered their impact on stroke prognosis. Therefore, we intended to evaluate the impact of HDP on short- and long-term outcomes of pregnancy-associated hemorrhagic stroke (HS).MethodsWe conducted a retrospective analysis of patients admitted to our hospital from May 2009 to December 2021 with a diagnosis of pregnancy-associated HS. After dividing patients into two groups by the presence of a diagnosis of HDP or not, the short- (at the time of discharge) and long-term (after discharge follow-up) outcomes were compared by mRS (modified Rankin Scale) scores, and poor functional outcome defined as mRS > 2. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were reported.ResultsTwenty-two HDP and 72 non-HDP pregnancy-associated HS patients were enrolled and follow-up after 4.7 ± 3.6 years. There was no significant difference between the two groups regarding short-term outcomes, but patients with HDP were more likely to reach poor functional outcomes at long-term follow-up (aOR = 4.47, 95% CI = 1.28–15.67, p = 0.019).ConclusionsIn this retrospective study, women with hypertension disorders of pregnancy did not show worse short-term outcomes of pregnancy-associated hemorrhagic stroke compared to those without but had poorer long-term functional outcomes. This underlines the importance of prevention, recognition, and treatment of hypertension disorders in these women.

ObjectiveUmbilical cord mesenchymal stem cells (UCMSCs) have significant regenerative, tissue repair, and immunomodulatory properties that can help reduce inflammatory responses in patients with ankylosing spondylitis (AS). In this study, we used a combination of bovine proteoglycan and dimethyldioctadecylammonium (DDA) to establish a mouse model of proteoglycan-induced spondylitis (PGISp). To evaluate the therapeutic effects of UCMSCs, we treated PGISp mice with different doses of hUCMSCs via tail vein injection.MethodsAt week 13, the PGISp mice exhibited thickened, erythematous paws, erythema in the extremities, and lameness. CT scans revealed necrotic lysis of chondrocytes, formation of fissures, visible hemorrhage, connective tissue hyperplasia, and focal infiltration of lymphocytes in the intervertebral discs. At week 14, the PGISp mice were randomly divided into three groups and administered different doses of hUCMSCs (0.25, 0.5, and 1.0×107 cells/kg, iv, QOW×2, n=10). To assess the therapeutic effects of hUCMSCs, we evaluated Th cell subsets in the spleen, spleen and thymus coefficients, peripheral blood inflammatory factors, and pathological and imaging observations of the spines and lumbar spines in the PGISp mice.ResultsThe results demonstrated that injection of hUCMSCs shifted the balance axis between Th1 and Th2 cells in the spleen towards Th2 cells. Moreover, the spleen coefficient and levels of inflammatory cytokines (TNF-α and CCL-2) in the serum decreased after hUCMSC injection. CT imaging and pathological analysis indicated that hUCMSC treatment inhibited ectopic osteogenesis and maintained clear small joint gaps, which slowed down the progression of structural lesions in the disc, nucleus pulposus, fibrous ring, and cartilage in PGISp mice.ConclusionAdministering hUCMSCs at the 14th week after modeling proved to be an effective treatment for PGISp mice. This experiment offers a valuable reference for the pre-clinical use of hUCMSCs in the treatment of AS.

Echolalia, the echoing of prior speech, is a typical characteristic of autism. Long considered meaningless repetition to be avoided, echolalia may in fact be used functionally in autism. This paper explores the functions of echolalia by children with autism. Based on two prior studies, we designed an elicitation task involving images of 12 professions (teacher) and 12 objects (birthday cake) commonly associated with given conventionalized expressions in Mandarin (e.g., “sheng ri kuai le!” ‘Happy birthday!’). Eight Chinese children with autism (mean age: 55.50 ± 8.64) were asked to name and describe these images. All our participants produced a relatively high proportion of echolalia, mostly for naming, description, and topic development, a small percentage being used as conversation maintenance strategy or as cognitive strategy. This indicates that echolalia is often used communicatively in autism speech.

Due to the influences of buildings, geographical and geomorphological environments, road conditions, etc., the probabilities and numbers of casualties in different areas after an earthquake are different. Accordingly, we propose the concept of the lethal level, which attains different grades representing the mortality rate of differing intensities. Different regions have unique lethal levels, and regional lethal levels are affected mainly by the proportion of each building type and the corresponding lethal level, as different types of buildings also have unique lethal levels. Based on data of 52 historical earthquake disasters, we constructed a lethal level calculation model and obtained the lethal level of each building type. The results reveal that the lethal level ranges of different building types are fixed and unequal; moreover, the ranges of different building types overlap each other. The lethal level range of adobe structures is 0.85–1, that of civil structures is 0.75–0.95, that of brick-wood structures is 0.6–0.9, that of brick-concrete structures is 0.33–0.6, that of wood structures is 0.2–0.35, and that of reinforced concrete structures is 0.1–0.25. Based on the lethal levels of these building types, the overall level of a region can be quantified and graded, and this classification does not depend on the geographical location or administrative boundaries. In pre-earthquake evaluation efforts, the lethal level of an area can be derived through field research. After an earthquake, the number of casualties can be quickly assessed based on the mortality rate corresponding to the intensity of the area. This approach can further provide scientific support for risk zoning and risk assessment research.

ObjectiveTo assess the outcome of a free preputial tube graft coupled with urethral plate urethroplasty combined with a Buck's fascia integral covering (BFIC) for the single-stage repair of severe hypospadias in children.Materials and methodsA retrospective study was performed on 40 children with hypospadias who were treated in our hospital from December 2017 to February 2022. The inclusion criteria were as follows: (1) the patient had proximal hypospadias, or penile curvature over 30° after degloving the penis; and (2) the patient underwent surgery for hypospadias for the first time. A free preputial tube graft coupled with urethral plate urethroplasty combined with a Buck's fascia integral covering was performed, and all patients were followed up for more than 6 months.ResultsAfter degloving the foreskin, the urethral orifice was retracted to the perineum and scrotum in 20 cases, penoscrotal in 8 cases, and penile in 12 cases. Single-stage repair was achieved without complications in 34 (85%) patients. The remaining six patients experienced postoperative complications: urethrocutaneous fistula occurred in five cases and glans dehiscence with urethrocutaneous fistula in one case. No urethral diverticulum occurred in any case. A neomeatus with a vertically oriented slit-like appearance was achieved at the tip of the glans in all cases, with one exception.ConclusionThe single-stage operation with a free preputial tube graft coupled with urethral plate urethroplasty combined with a Buck's fascia integral covering in the treatment of severe hypospadias achieves favorable functional and cosmetic outcomes.

From accumulation mechanisms and the identification of effective faults, hydrocarbon distribution in slope areas of petroliferous basins is assessed. In this study, we superimpose two methods to develop a set of key methods, which can identify effective faults for hydrocarbon accumulation in slope areas. The first of this set of methods includes locating the distribution area of the connected sand bodies and paleotectonic ridges overlying the formation where the sand bodies are located, which aids determining the lateral migration path of hydrocarbons in slope areas. The second set of methods includes identifying the lateral sealing parts of faults that are oriented perpendicular or oblique to the channel sand bodies, thereby determining the faults that are effective for hydrocarbon accumulation. By applying these methods, we identify the effective faults in the first member of the Nantun Formation (K1n1) on the Wunan slope of the Wuerxun Depression in the Hailar Basin. The results show that the effective faults in K1n1 are located mainly in its middle and northern parts, with a few distributed in the south-central part. This is conducive to reservoir development, since hydrocarbons which were generated in the western trough source rocks of K1n1, accumulated in the nearby trap formed from a suitable configuration of the fault and sand body of K1n1. This is consistent with previous exploration data, and the observation that hydrocarbons discovered in K1n1 on the Wunan slope are mainly distributed in the middle and northern parts of the region, and a small amount occur in the south-central part. The results show that this set of methods is feasible for determining effective faults for hydrocarbon accumulation in slope areas.

ObjectiveThis study explored the underlying therapeutic mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) for ischemic stroke (IS), and determined the optimal administration time windows and dose-effect relationship.MethodsThe levels of SDF-1α, IL-10, IL-6, TNF-α, BDNF, IL-1β, and VEGF-A factors in serum and brain tissue lysate were measured by ELISA. The pathological status of brain tissues was evaluated by Hematoxylin-Eosin (HE) staining, and apoptosis of nerve cells was detected by tunel. The protein expression of CXCR-4, NeuN, and Nestin in the brain tissues was assessed through immunofluorescence. The balance beam, forelimb muscle strength, and limb placement were tested on MCAO rats at different time points and doses. The infarct area of the rat brain tissues was measured at the end of the experiment.ResultsThe hUCMSC treatment during the acute phase of MCAO significantly reduced the secretion of IL-6, TNF-α, IL-1β but increased IL-10 in serum, and the levels of SDF-α and BDNF in serum and brain tissues lysate were also increased. The pathological results showed that there were more neurons in the treatment group compared to the model group. Immunofluorescence assays showed that the expression of CXCR4、Nestin、NeuN was relatively higher than that in the model group. The d4 and d7 treatment significantly improves the motor function, promotes the recovery of forelimb muscle strength, increases the forelimb placement rate and reduces the scope of cerebral infarction, but the d14 treatment group has less therapeutic effect compared to the d4 and d7 treatment. The 2×107/kg treatment showed the best therapeutic effect, followed by the 1×107/kg treatment, and the worst is 0.5×107/kg treatment from the test of balance beam, forelimb muscle strength, limb placement and the infarct area of the rat brain tissues.ConclusionThe hUCMSCs can inhibit the infiltration of inflammatory cells in the brain tissue, and promote the repair of brain tissue structure and function. Early intervention by injecting high-dose of hUCMSCs can significantly improve the recovery of neurological/motor function and reduce the size of cerebral infarction in rats.

BackgroundThe predictive effects of liver metastases for immune-checkpoint inhibitors (ICIs) and the relationship between tumor mutational burden (TMB) and liver metastases (LM) remain unclear.MethodsA systematic review and meta-analysis were conducted to explore the heterogeneity of ICIs efficacy between patients with or without LM. A pan-cancer cohort of 1,661 patients who received ICIs was downloaded and analyzed to assess the association between TMB and LM.ResultsOf 21053 studies identified in our search, eight single-arm studies and 24 randomized controlled trials were included. Overall, 17957 patients with advanced or metastatic cancers (4805 patients (26.8%) with LM and 13151 patients (73.2%) without LM) were enrolled. The pooled objective response rate (ORR) was 8.5% (95% CI 4%–13%) in the LM group versus 21% (95% CI 16%–21%) in the non-LM group. The pooled hazard ratio (HR) for death was 0.85 (95% CI 0.80–0.90) in the LM group treated with ICIs compared with the standard of care. In patients without LM who were treated with ICIs, the pooled HR for death was 0.78 (95% CI 0.73–0.82) compared with the standard of care. The difference in efficacy between patients with or without LM treated with ICIs was significant (p=0.04). Pan-cancer analysis revealed that the TMB-high rate was 10.8% in liver metastatic lesions versus 21.4% in other metastatic lesions (p=0.004). In addition, TMB was also significantly associated with OS as a binary cutoff (p=0.05) and was an independent prognostic variable (HR=0.98, P=0.047) as a continuous variable in patients with LM.ConclusionsIn patients with LM, the efficacy of immunotherapy was attenuated, but TMB-high could predict better survival outcomes.

In invertebrates, hemocytes are the key factors in innate immunity. However, the types of invertebrate immune hemocytes are unclassified due to the limitation of morphological classification. To determine the immune hemocytes of crustaceans, the heterogeneity of hemocytes of shrimp Marsupenaeus japonicus and crayfish Procambarus clarkii, two representative crustacean species, were characterized in this study. The results of single-cell RNA sequencing indicated that shrimp and crayfish contained 11 and 12 types of hemocytes, respectively. Each of different types of hemocytes specifically expressed the potential marker genes. Based on the responses of shrimp and crayfish to the infection of white spot syndrome virus (WSSV) and the challenge of lipopolysaccharide (LPS), four types of immune hemocytes of crustaceans were classified, including semi-granular hemocytes involved in antimicrobial peptide production, granular hemocytes responsible for the production of antimicrobial peptides, hemocytes related to cell proliferation and hemocytes in immunity-activated state. Therefore, our study provided the first classification of crustacean hemocytes as well as of immune hemocytes of crustaceans at the single-cell resolution, which would be helpful to understand the innate immunity of invertebrates.

BackgroundThe wave of education information based on the “Internet+” has swept the world, and the traditional teaching mode can no longer meet the new needs of education teaching, so the teaching mode of “MOOC+ flipped classroom” has attracted widespread attention educators.ObjectiveThis study explores the effect of “MOOC+ flipped classroom” on the teaching design and application of basketball courses in colleges and universities from the perspective of education modernization in order to promote the development of students’ core literacy and provide a more theoretical basis and practical support for the in-depth research and promotion of “MOOC+ flipped classroom” teaching mode.MethodsThis study adopts a quasi-experimental design to study the teaching of basketball courses in colleges and universities based on “MOOC +flipped classroom.” The experimental class adopted “MOOC+ flipped classroom” teaching (34 students), and the control group adopted traditional classroom teaching (30 students). Before and after the 16-week intervention, the student’s learning effects were measured by basketball skill level assessment, Cooperation Ability Scale for University Students, Utrecht Work Engagement Scale-student, and Self-regulated Learning Scale, and the data were analyzed by independent sample t-test and repeated-measures ANOVA.Conclusion(1) Compared with the traditional classroom teaching mode, the “MOOC+ flipped Classroom” teaching mode is innovative in terms of teaching philosophy, teaching resources, and teaching methods, which promotes the change of education informatization and further promotes the realization of education modernization. (2) The “MOOC+ flipped classroom”-based teaching design for basketball courses benefits students’ basketball skill level, study engagement, cooperation ability, and self-regulated learning ability, thus effectively promoting the students’ core literacy.

For locally advanced (T3-4/N+M0) rectal cancer (LARC), neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is the standard treatment. It was demonstrated to decrease the local recurrence rate and increase the tumor response grade. However, the distant metastasis remains an unresolved issue. And the demand for anus preservation and better quality of life increases in recent years. Radiotherapy and immunotherapy can be supplement to each other and the combination of the two treatments has a good theoretical basis. Recently, multiple clinical trials are ongoing in terms of the combination of nCRT and immunotherapy in LARC. It was reported that these trials achieved promising short-term efficacy in both MSI-H and MSS rectal cancers, which could further improve the rate of clinical complete response (cCR) and pathological complete response (pCR), so that increase the possibility of ‘Watch and Wait (W&W)’ approach. However, the cCR and pCR is not always consistent, which occurs more frequent when nCRT is combined with immunotherapy. Thus, the efficacy evaluation after neoadjuvant therapy is an important issue for patient selection of W&W approach. Evaluating the cCR accurately needs the combination of multiple traditional examinations, new detective methods, such as PET-CT, ctDNA-MRD and various omics studies. And finding accurate biomarkers can help guide the risk stratification and treatment decisions. And large-scale clinical trials need to be performed in the future to demonstrate the surprising efficacy and to explore the long-term prognosis.

Purpose: This study aims to develop a prediction model to categorize the risk of early death among breast cancer patients with bone metastases using machine learning models.Methods: This study examined 16,189 bone metastatic breast cancer patients between 2010 and 2019 from a large oncological database in the United States. The patients were divided into two groups at random in a 90:10 ratio. The majority of patients (n = 14,582, 90%) were served as the training group to train and optimize prediction models, whereas patients in the validation group (n = 1,607, 10%) were utilized to validate the prediction models. Four models were introduced in the study: the logistic regression model, gradient boosting tree model, decision tree model, and random forest model.Results: Early death accounted for 17.4% of all included patients. Multivariate analysis demonstrated that older age; a separated, divorced, or widowed marital status; nonmetropolitan counties; brain metastasis; liver metastasis; lung metastasis; and histologic type of unspecified neoplasms were significantly associated with more early death, whereas a lower grade, a positive estrogen receptor (ER) status, cancer-directed surgery, radiation, and chemotherapy were significantly the protective factors. For the purpose of developing prediction models, the 12 variables were used. Among all the four models, the gradient boosting tree had the greatest AUC [0.829, 95% confident interval (CI): 0.802–0.856], and the random forest (0.828, 95% CI: 0.801–0.855) and logistic regression (0.819, 95% CI: 0.791–0.847) models came in second and third, respectively. The discrimination slopes for the three models were 0.258, 0.223, and 0.240, respectively, and the corresponding accuracy rates were 0.801, 0.770, and 0.762, respectively. The Brier score of gradient boosting tree was the lowest (0.109), followed by the random forest (0.111) and logistic regression (0.112) models. Risk stratification showed that patients in the high-risk group (46.31%) had a greater six-fold chance of early death than those in the low-risk group (7.50%).Conclusion: The gradient boosting tree model demonstrates promising performance with favorable discrimination and calibration in the study, and this model can stratify the risk probability of early death among bone metastatic breast cancer patients.

ObjectiveTo investigate the efficacy of indirubin combined with human umbilical cord mesenchymal stem cells (hUC-MSCs) in the treatment of psoriatic lesions in BALB/c mice and to explore the related mechanism of indirubin in the treatment of psoriasis.MethodsA BALB/c mouse psoriasis model induced by imiquimod was established and randomly divided into the control group, model group, indirubin group, hUC-MSCs group, and indirubin combined with hUC-MSCs group. Psoriasis area and severity index (PASI) score was used to observe skin lesion changes in the psoriasis-like mouse model. The epidermal scale, the degree of keratinization, and the infiltration of inflammatory cells were observed by hematoxylin eosin (HE) staining. The concentrations of TNF-α, IFN-γ, IL-17A, and IL-23 in serum of mice were measured using enzyme-linked immunosorbent assay (ELISA).ResultsThe PASI integral trend chart indicates that hUC-MSCs and indirubin and the combination of drugs could relieve the appearance of skin lesions and accelerate the recovery of skin lesions. The indirubin group had the best effect in improving the scale of skin lesions. HE staining showed that the number of parakeratosis cells in the three treatment groups was significantly reduced, the degree of erythrocyte extravasation dermis hyperplasia and inflammatory cell infiltration was significantly lower than that in the model group, and the skin thickness and spleen index of the combined treatment group exhibited the most noticeable improvement. ELISA showed that the concentrations of TNF-α, IFN-γ, IL-17A, and IL-23 in serum of mice in the hUC-MSCs treatment group, indirubin group, and combined administration group were all decreased compared with those in the model group, and the concentrations of IFN-γ, IL-17A, and IL-23 could be decreased significantly in the indirubin group.ConclusionsBoth hUC-MSCs and indirubin can effectively reduce psoriasis-like lesions in BALB/c mice, and the combined administration of these drugs has the best effect.

BackgroundSignificantly improved survival in patients with pulmonary hypertension (PH) has raised interest in maintaining a good quality of long-term survivorship. In this study, health-related quality of life (HRQOL) measurement was used to assess the long-term changes of physical and mental outcomes.MethodsA total of 559 consecutive inpatients with PH completed generic HRQOL (Short Form-36) who were diagnosed with PH by right heart catheterization. Assessments were carried out at short-term (1 year), midterm (3 years), and long-term (5 years) follow-ups.ResultsPatients with PH suffered more severe impairments in both physical and emotional domains than the U.S. population normative values. Patients with PH due to chronic lung disease had the worst physical component summary (PCS) score, but there was no difference in mental component summary (MCS) score among different PH types. A reduced PCS score was correlated with WHO FC severity and pulmonary vascular resistance (PVR). The Z score showed that the changing trend of mental conditions continuously declined from baseline to midterm and long-term follow-ups, but the PCS score seemed to be stable or improved. Cox regression analysis indicated increased baseline PVR and WHO FC III and IV, and decreased physical subscale of role physical, mental subscale of social functioning, and the MCS score have increased risk of mortality in the long-term follow-up.ConclusionPatients with PH have poor HRQOL. The long-term change of physical status seemed to be stable, but the mental state was continuously worse. These suggested identifying and intervening mental health progresses is a noteworthy issue in PH chronic management.

Chimeric antigen receptor T cell (CAR-T) therapy has emerged as highly effective in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), but only about 40% patients have achieved sustained responses. Here, we conducted a phase II clinical trial testing efficacy and toxicities of CAR-T therapy in R/R non-Hodgkin’s lymphoma patients (NCT03196830). Among enrolled patients, 33 R/R DLBCL patients pretreated with DFC (decitabine, fludarabine plus cyclophosphamide) lymphodepletion chemotherapy and infused with tandem CD19-CD22 based CAR-T cells were drawn out for efficacy and toxicities of CAR-T therapy evaluation. With a median follow-up of 10.9(0.6-29.0) months, the best overall response and complete remission (CR) rates were 90.9% and 63.6%, respectively. The median progression-free survival (PFS) was 10.2 months and overall survival (OS) was undefined. The 2-year OS and PFS rates were 54.3% and 47.2%, respectively. No severe grade 4 cytokine release syndrome (CRS) was observed and grade 3 CRS was observed in only 7 patients; 3 patients developed mild immune effect or cell-associated neurotoxic syndrome. All toxicities were transient and reversible and no CAR-T-related mortality. Further subgroup analysis showed that achieving CR was an independent prognostic factor associated with favorable PFS and OS. The 2-year OS and PFS for patients who achieved CR within 3 months (undefined versus undefined P=0.021 and undefined versus undefined P=0.036) or during the follow-up period were significantly longer than those who did not (undefined versus 4.6 months P < 0.0001 and undefined versus 2.0months P

DC voltage utilization and AC voltage harmonics are important evaluation indexes for Auxiliary Power Converter in Railway Applications. To improve the above two indicators, a novel switch-mode modulation method and quasi-PR control strategy for Buck-H three-phase inverter is proposed in this paper. The Buck-H three-phase inverter integrates the AC side filter circuit into the DC Buck circuit, which reduces the volume of the filter capacitor and improves the filtering effect. This novel switch-mode modulation method uses only one high frequency switch per phase, which reduces the switching losses and thereby increases overall efficiency. In addition, this switch-mode modulation absence of shoot-through menace eliminates the dead time requirement. Meanwhile, the quasi-proportional-resonance (PR) controller and its control parameters are optimized to improve the AC voltage tracking performance. The influence of PR control parameters on system performance is analyzed in detail. The proposed switch-mode modulation method and control method can effectively reduce the harmonic distortion rate of the system. The effectiveness is verified through the StarSim hardware-in-the-loop experimental results.

Rapid growth is one of the most important economic traits in broiler breeding programs. Identifying markers and genes for growth traits may not only benefit marker-assisted selection (MAS)/genomic selection (GS) but also provide important information for understanding the genetic architecture of growth traits in broilers. In the present study, an F2 resource population derived from a cross between the broiler and Baier yellow chicken (a Chinese local breed) was used and body weights from 1 to 12 weeks of age [body weight (BW) 1–BW12)] were measured. A total of 519 F2 birds were genome re-sequenced, and a combination of genome-wide association study (GWAS) and selective sweep analysis was carried out to characterize the genetic architecture affecting chicken body weight comprehensively. As a result, 1,539 SNPs with significant effects on body weights at different weeks of age were identified using a genome-wide efficient mixed-model association (GEMMA) package. These SNPs were distributed on chromosomes 1 and 4. Besides, windows under selection identified for BW1–BW12 varied from 1,581 to 2,265. A total of 42 genes were also identified with significant effects on BW1–BW12 based on both GWAS and selective sweep analysis. Among these genes, diacylglycerol kinase eta (DGKH), deleted in lymphocytic leukemia (DLEU7), forkhead box O17 (FOXO1), karyopherin subunit alpha 3 (KPNA3), calcium binding protein 39 like (CAB39L), potassium voltage-gated channel interacting protein 4 (KCNIP4), and slit guidance ligand 2 (SLIT2) were considered as important genes for broiler growth based on their basic functions. The results of this study may supply important information for understanding the genetic architecture of growth traits in broilers.

Antrodia camphorata is rich in a variety of bioactive ingredients; however, the utilization efficiency of the residue of A. camphorata is low, resulting in serious waste. It is necessary to deeply study the functional components of A. camphorata residues to achieve high-value utilization. In this study, the components, structural characteristics, and functional properties of alkali-extracted dietary fiber extracted from residues of A. camphorata (basswood and dish cultured fruiting body, respectively) were investigated. There were similar components and structural characteristics of ACA-DK (extract from basswood cultured) and ACA-DF (extract from dish cultured). The two alkali-extracted dietary fiber were composed of mainly cellulose and xylan. However, ACA-DK has better adsorption capacities than ACA-DF on lipophilic substances such as oil (12.09 g/g), cholesterol (20.99 mg/g), and bile salts (69.68 mg/g). In vitro immunomodulatory assays stated that ACA-DK had a good effect on promoting the proliferation of RAW 264.7 cells and can activate cell phagocytosis, NO synthesis, and other immune capabilities. The edible fungus A. camphorata is a good source of functional dietary fiber. The alkali-extracted dietary fiber of A. camphorata might be used as a functional ingredient in the medicine and food industry.

Erythrocytes undergo certain morphological changes resembling apoptosis during senescence or in an abnormal state/site, which is termed eryptosis. This process is characterized by phosphatidylserine (PS) exposure, membrane blebbing, and cell shrinkage. Eryptotic erythrocytes are subsequently removed via macrophage-mediated efferocytosis. In hemorrhagic stroke (HS), blood within an artery rapidly bleeds into the brain tissue or the subarachnoid space, resulting in severe neurological deficits. A hypoxic, over-oxidative, and pro-inflammatory microenvironment in the hematoma leads to oxidative stress, hyperosmotic shock, energy depletion, and Cl– removal in erythrocytes, which eventually triggers eryptosis. In addition, eryptosis following intracerebral hemorrhage favors hematoma clearance, which sheds light on a common mechanism of intrinsic phagocytosis. In this review, we summarized the canonical mechanisms of eryptosis and discussed its pathological conditions associated with HS. Understanding the role of eryptosis in HS may uncover additional potential interventions for further translational clinical research.

Alisol B 23-Acetate (AB23A) is a naturally occurring triterpenoid, which can be indicated in the rhizome of medicinal and dietary plants from Alisma species. Previous studies have demonstrated that AB23A could inhibit intestinal permeability by regulating tight junction (TJ)-related proteins. Even so, the AB23A protective mechanism against intestinal barrier dysfunction remains poorly understood. This investigation seeks to evaluate the AB23A protective effects on intestinal barrier dysfunction and determine the mechanisms for restoring intestinal barrier dysfunction in LPS-stimulated Caco-2 monolayers. According to our findings, AB23A attenuated the inflammation by reducing pro-inflammatory cytokines production like IL-6, TNF-α, IL-1β, and prevented the paracellular permeability by inhibiting the disruption of TJ in LPS-induced Caco-2 monolayers after treated with LPS. AB23A also inhibited LPS-induced TLR4, NOX1 overexpression and subsequent ROS generation in Caco-2 monolayers. Transfected with NOX1-specific shRNA diminished the up-regulating AB23A effect on ZO-1 and occludin expression. Moreover, transfected with shRNA of TLR4 not only enhanced ZO-1 and occludin expression but attenuated NOX1 expression and ROS generation. Therefore, AB23A ameliorates LPS-induced intestinal barrier dysfunction by inhibiting TLR4-NOX1/ROS signaling pathway in Caco-2 monolayers, suggesting that AB23A may have positive impact on maintaining the intestinal barrier’s integrity.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was initially described to target the respiratory system and now has been reported to infect a variety of cell types, including cardiomyocytes, neurons, hepatocytes, and gut enterocytes. However, it remains unclear whether the virus can directly infect human embryonic stem cells (hESCs) or early embryos. Herein, we sought to investigate this question in a cell-culture system of hESCs. Both the RNA and S protein of SARS-CoV-2 were detected in the infected hESCs and the formation of syncytium was observed. The increased level of subgenomic viral RNA and the presence of dsRNA indicate active replication of SARS-CoV-2 in hESCs. The increase of viral titers in the supernatants revealed virion release, further indicating the successful life cycle of SARS-CoV-2 in hESCs. Remarkably, immunofluorescence microscopy showed that only a small portion of hESCs were infected, which may reflect low expression of SARS-CoV-2 receptors. By setting |log2 (fold change)| > 0.5 as the threshold, a total of 1,566 genes were differentially expressed in SARS-CoV-2-infected hESCs, among which 17 interferon-stimulated genes (ISGs) were significantly upregulated. Altogether, our results provide novel evidence to support the ability of SARS-CoV-2 to infect and replicate in hESCs.

Pulmonary arterial hypertension (PAH) is a chronic, lethal pulmonary disease characterized by pulmonary vascular remodeling. It leads to malignant results, such as rupture of pulmonary arterial dissection, dyspnea, right heart failure, and even death. Previous studies have confirmed that one of the main pathological changes of this disease is abnormal mitochondrial dynamics, which include mitochondrial fission, fusion, and autophagy that keep a dynamic balance under certain physiological state. Dynamin-related protein 1 (Drp1), the key molecule in mitochondrial fission, mediates mitochondrial fission while also affecting mitochondrial fusion and autophagy through numerous pathways. There are various abnormalities of Drp1 in PAH pathophysiology, including Drp1 overexpression and activation as well as an upregulation of its outer mitochondrial membrane ligands. These aberrant alterations will eventually induce the development of PAH. With the process of recent studies, the structure and function of Drp1 have been gradually revealed. Meanwhile, inhibitors targeting this pathway have also been discovered. This review aims to shed more light on the mechanism of Drp1 and its inhibitors in the abnormal mitochondrial dynamics of PAH. Furthermore, it seeks to provide more novel insights to clinical therapy.

Frailty is a critical aging-related syndrome but the underlying metabolic mechanism remains poorly understood. The aim of this study was to identify novel biomarkers and reveal potential mechanisms of frailty based on the integrated analysis of metabolome and gut microbiome. In this study, twenty subjects consisted of five middle-aged adults and fifteen older adults, of which fifteen older subjects were divided into three groups: non-frail, pre-frail, and frail, with five subjects in each group. The presence of frailty, pre-frailty, or non-frailty was established according to the physical frailty phenotype (PFP). We applied non-targeted metabolomics to serum and feces samples and used 16S rDNA gene sequencing to detect the fecal microbiome. The associations between metabolites and gut microbiota were analyzed by the Spearman’s correlation analysis. Serum metabolic shifts in frailty mainly included fatty acids and derivatives, carbohydrates, and monosaccharides. Most of the metabolites belonging to these classes increased in the serum of frail older adults. Propylparaben was found to gradually decrease in non-frail, pre-frail, and frail older adults. Distinct changes in fecal metabolite profiles and gut microbiota were also found among middle-aged adults, non-frail and frail older subjects. The relative abundance of Faecalibacteriu, Roseburia, and Fusicatenibacter decreased while the abundance of Parabacteroides and Bacteroides increased in frailty. The above altered microbes were associated with the changed serum metabolites in frailty, which included dodecanedioic acid, D-ribose, D-(-)-mannitol, creatine and indole, and their related fecal metabolites. The changed microbiome and related metabolites may be used as the biomarkers of frailty and is worthy of further mechanistic studies.

Depression and anxiety are common in patients with COPD (chronic obstructive pulmonary disease), and anxiety and depression can increase the risk of hospitalization and the acute exacerbation of chronic obstructive pulmonary disease. The relationship between the frequency of hospitalization for acute exacerbation of COPD (AECOPD) and the anxiety and depression of patients is not fully understood. This study aims to analyze the relationship between the frequency of hospitalizations and anxiety and depression of patients of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). A collection of 309 AECOPD patients admitted to the emergency department in our hospital from 2019 to 2020 were divided into anxiety group A and depression group D according to the Hospital Anxiety and Depression Scale (HADS) score and divided into A1 and D1 negative groups (≤7 Score), A2 and D2 suspicious groups (8–10 points), A3 and D3 confirmed groups (≥11 points) for paired analysis of anxiety and depression correlation and difference and comparison of the frequency of hospitalization in each group within 2 years. The results found that anxiety and depression were significantly positively correlated (r = 0.654, p = 0.000). Intra-group comparison shows that the difference between the anxiety-diagnosed and non-diagnosed groups and the depression subgroups are statistically p < 0.05; the comparison between the anxiety subgroup and the depression subgroup showed that there was a statistical difference between the confirmed group and the non-diagnosed group (p < 0.01). In short, AECOPD anxiety is positively correlated with depression, and depression is affected by the frequency of hospitalization earlier and gradually, and anxiety should be prioritized in the acute phase.

Dehydrocostus lactone (DCL) is a major sesquiterpene lactone isolated from Aucklandia lappa Decne, a traditional Chinese herbal medicine that used to treat gastrointestinal diseases. This study aimed to examine the therapeutic effects of DCL on dextran sulfate sodium (DSS)-induced colitis with a focus on identifying the molecular mechanisms involved in DCL-mediated anti-inflammatory activity in macrophages. First, oral administration of DCL (5–15 mg/kg) not only ameliorated symptoms of colitis and colonic barrier injury, but also inhibited the expression of proinflammatory cytokines and myeloperoxidase in colon tissues in DSS-challenged mice. Furthermore, DCL also exhibited significant anti-inflammatory activity in LPS/IFNγ-stimulated RAW264.7 macrophages. Importantly, DCL significantly suppressed the phosphorylation and degradation of IκBα and subsequent NF-κB nuclear translocation, and enhanced the nuclear accumulation of Nrf2 in LPS/IFNγ-treated RAW264.7 cells. Mechanistically, DCL could directly interact with IKKα/β and Keap1, thereby leading to the inhibition of NF-κB signalling and the activation of Nrf2 pathway. Furthermore, DCL-mediated actions were abolished by dithiothreitol, suggesting a thiol-mediated covalent linkage between DCL and IKKα/β or Keap1. These findings demonstrated that DCL ameliorates colitis by targeting NF-κB and Nrf2 signalling, suggesting that DCL may be a promising candidate in the clinical treatment of colitis.

Evidence suggests that the accumulation of lipid drots (LDs) accelerates damage to mitochondria and increases the release of inflammatory factors. These have been implicated as a mechanism underlying neurodegenerative diseases or tumors and aging-related diseases such as postoperative cognitive dysfunction (POCD), nevertheless, accumulation of lipid droplets has not been extensively studied in the central nervous system (CNS). Here, we found that after surgery, there was activation of astrocytes and lipid accumulation in the hippocampus. However, cannabinoid receptor type II (CB2R) activation significantly reduced lipid accumulation in astrocytes and change the expression of genes related to lipid metabolism. CB2R reduces the release of the inflammatory factors interleukin-1 beta (IL-1β) and interleukin 6 (IL-6) in peripheral serum and simultaneously improves cognitive ability in mice with POCD. Further research on mechanisms indicates that CB2R activation promotes the nuclear entry of the bHLH-leucine zipper transcription factor, the transcription factor EB (TFEB), and which is a master transcription factor of the autophagy–lysosomal pathway, also reduces TFEB-S211 phosphorylation. When CB2R promotes TFEB into the nucleus, TFEB binds at two sites within promoter region of PGC1α, promoting PGC1α transcription and accelerating downstream lipid metabolism. The aforementioned process leads to autophagy activation and decreases cellular lipid content. This study uncovers a new mechanism allowing CB2R to regulate lipid metabolism and inflammation in POCD.

Complete trajectory planning includes path planning, inverse solution solving and trajectory optimization. In this paper, a highly smooth and time-saving approach to trajectory planning is obtained by improving the kinematic and optimization algorithms for the time-optimal trajectory planning problem. By partitioning the joint space, the paper obtains an inverse solution calculation based on the partitioning of the joint space, saving 40% of the inverse kinematics solution time. This means that a large number of computational resources can be saved in trajectory planning. In addition, an improved sparrow search algorithm (SSA) is proposed to complete the solution of the time-optimal trajectory. A Tent chaotic mapping was used to optimize the way of generating initial populations. The algorithm was further improved by combining it with an adaptive step factor. The experiments demonstrated the performance of the improved SSA. The robot’s trajectory is further optimized in time by an improved sparrow search algorithm. Experimental results show that the method can improve convergence speed and global search capability and ensure smooth trajectories.

Nuclear lamins, known as type 5 intermediate fibers, are composed of lamin A, lamin C, lamin B1, and lamin B2, which are encoded by LMNA and LMNB genes, respectively. Importantly, mutations in nuclear lamins not only participate in lipid disorders but also in the human diseases, such as lipodystrophy, metabolic-associated fatty liver disease, and dilated cardiomyopathy. Among those diseases, the mechanism of lamin has been widely discussed. Thereby, this review mainly focuses on the regulatory mechanism of the mutations in the lamin gene in lipid alterations and the human diseases. Considering the protean actions, targeting nuclear lamins may be a potent therapeutic avenue for lipid metabolic disorders and human diseases in the future.

In mammals, bile acid (BA) concentrations are regulated largely by the gut microbiota, and a study has shown that some metabolic responses to the gut microbiota are conserved between zebrafish and mice. However, it remains unknown whether the influence of specific intestinal microbes on BA metabolism is conserved between higher and lower vertebrates (i.e., mammals and fish). In the present study, Citrobacter freundii GC01 isolated from the grass carp (Ctenopharyngodon idella) intestine was supplemented to the fish and mice feed. We found the changes in the bile acid profile, especially significant changes in secondary BAs in both grass carp and mice fed on C. freundii. Also, lipid metabolism was significantly affected by C. freundii. Analysis of liver transcriptome sequencing data and validation by RT-qPCR revealed that the CYP7A1 gene was significantly up-regulated in both grass carp and mice. In addition, the overexpression of HNF4B from grass carp resulted in a significant increase in the expression level of CYP7A1. Generally, our results suggest that the metabolism of BAs by intestinal microbiota is conserved across vertebrates. Furthermore, specific intestinal bacteria may regulate the bile salt synthesis through CYP7A1 and that HNF4B might be an important regulator of BA metabolism in fish.

BackgroundA preliminary study by our group revealed that the deficiency of EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT) impaired regulatory T-cell differentiation in autoimmune hepatitis. Nevertheless, the prognostic value of EOGT in advanced hepatocellular carcinoma (HCC) and its relationship with immune infiltration remain obscured.MethodsInitially, EOGT expression was evaluated by Oncomine, TIMER, GEO, and UALCAN databases. Besides, the prognostic potential of EOGT expression was analyzed using GEPIA, Kaplan–Meier plotter, CPTAC, Cox regression, and nomogram in HCC samples. Furthermore, we investigated the association between EOGT expression and tumor mutation burden, DNA methylation, and immune infiltration in addition to its possible mechanism via cBioPortal, TIMER, GEPIA, ESTIMATE, CIBERSORT, GSEA, STRING, and Cytoscape.ResultsThe expression of EOGT in HCC was significantly higher than that in normal tissues. Additionally, elevated EOGT expression was correlated with advanced tumor staging and linked to poor overall survival and relapse-free survival, serving as a significant unfavorable prognostic indicator in HCC patients. Remarkably, our results revealed that high-EOGT expression subgroups with elevated TP53 or low CTNNB1 mutations have worse clinical outcomes than the others. Regarding immune infiltration, immunofluorescent staining showed that immune cells in HCC were positive for EOGT. Besides, elevated EOGT expression was linked to exhausted T cells and immune suppressor cells in HCC samples. More importantly, the proportion of CD8+ T cells was reduced in HCC samples with a high level of EOGT expression, but EOGT did not exhibit prognostic potential in HCC samples with increased CD8+ T cells.ConclusionsEOGT may hold great potential as a novel biomarker to distinguish prognosis and immune profiles of HCC patients.

In this work, we studied the waveforms of all lightning discharges from about 15 min. Eighty-three percent of all lightning discharges contain particular waveforms called regular pulse bursts (RPBs), which have regular microsecond-scale electric or magnetic field pulses. Maximum proportion of RPBs occur in middle or rear of lightning discharges. Prior to or after RPBs, there is always a chaotic pulse period. The analysis indicated that RPBs are caused by a secondary discharge in the fractured old breakdown channel, likeness to dart-stepped leader occuring in negative cloud-to-ground discharge (-CG). Four types of RPBs, namely, category of normal RPBs, category of back RPBs, category of symmetric RPBs, and category of reversal RPBs, were sorted in the light of the evolution of the pulse amplitude, interval between neighboring pulses and pulse polarity. In addition, the difference between normal RPBs and back RPBs was considered to be caused by the distance between neighboring charge pockets and the magnitude of the charge in every charge pocket. The symmetric RPBs were considered to be caused by a discharge channel with a large central charge area. Reversal RPBs were considered to be caused by a bending channel or superposition of two or more RPBs. We located some RPBs in a typical intra-cloud flash (IC) in three-dimensional. The analysis showed that the developing velocity of RPBs ranged from approximately 1.2 × 106 m/s to 3.0 × 106 m/s, which slower less than both of the dart leader or dart-stepped leader process from previous studies. And we found it is several meters to dozens of meters that the lengths range of discharge step which between two adjacent pulses.