Development of an individualized stable and force-reducing lower-limb exoskeleton.

In this study, an individualized and stable passive-control lower-limb exoskeleton robot was developed. Users' joint angles and the center of pressure (CoP) of one of their soles were input into a convolutional neural network (CNN)-long short-term memory (LSTM) model to evaluate and adjust the exoskeleton control scheme. The CNN-LSTM model predicted the fitness of the control scheme and output the results to the exoskeleton robot, which modified its control parameters accordingly to enhance walking stability. The sole's CoP had similar trends during normal walking and passive walking with the developed exoskeleton; they-coordinates of the CoPs with and without the exoskeleton had a correlation of 91%. Moreover, electromyography signals from the rectus femoris muscle revealed that it exerted 40% less force when walking with a stable stride length in the developed system than when walking with an unstable stride length. Therefore, the developed lower-limb exoskeleton can be used to assist users in achieving balanced and stable walking with reduced force application. In the future, this exoskeleton can be used by patients with stroke and lower-limb weakness to achieve stable walking.

Early-life body mass index and the risk of six cardiovascular diseases: A Mendelian Randomization study.

BACKGROUND: Observational studies consistently indicate an association between early-life body mass index (BMI) and several cardiovascular diseases (CVDs). However, the causal relationship remains uncertain. The primary objective of this study was to assess the causal relationship between early-life BMI and six types of CVDs using the Mendelian Randomization (MR) approach. METHODS: The dataset for this study was derived from large-scale, summary-level Genome-Wide Association Studies. Specifically, the following datasets we used, early-life BMI (n = 61 111, age = 2-10), heart failure (HF) dataset (n = 977 323), atrial fibrillation (AF) dataset (n = 1 030 836), coronary artery disease (CAD) dataset (n = 184 305), peripheral artery disease (PAD) dataset (n = 243 060), deep venous thrombosis (DVT) dataset (n = 1 500 861) and myocardial infarction (MI) dataset (n = 638 000). Multiple MR methods were utilized to evaluate the causal relationship between exposure and outcomes, accompanied by sensitivity analysis. RESULTS: Early-life BMI positively correlates with the risk of developing the six distinct CVDs included in this study. Specifically, elevated BMI during childhood is associated with a 31.9% risk for HF (Odds ratio [OR] = 1.319, 95% CI [1.160 to 1.499], p = 2.33 × 10-5), an 18.3% risk for AF (R = 1.183, 95% CI [1.088 to 1.287], p = 8.22 × 10-5), an 14.8% risk for CAD (OR = 1.148, 95% CI [1.028 to 1.283], p = 1.47 × 10-2), a 40.5% risk for PAD (OR = 1.405, 95% CI [1.233 to 1.600], p = 3.10 × 10-7) and 12.0% risk for MI (OR = 1.120, 95% CI [1.017 to 1.234], p = 2.18 × 10-2). Interestingly, the risk for deep venous thrombosis only increased by 0.5% (OR = 1.005, 95% CI [1.001 to 1.008], p = 2.13 × 10-3). CONCLUSION: Genetically inferred early-life BMI is significantly associated with six distinct CVDs. This indicates that elevated early-life BMI is a significant risk factor for multiple cardiovascular disorders.

Effect of electroacupuncture combined with rehabilitation techniques on shoulder function in patients with rotator cuff injuries.

BACKGROUND: The rotator cuff is located below the acromion and deltoid muscles and comprises multiple tendons that wrap around the humeral head, maintaining shoulder joint stability. AIM: To explore the effect of electroacupuncture combined with rehabilitation techniques on shoulder function in patients with rotator cuff injuries. METHODS: We selected 97 patients with rotator cuff injuries treated in the People's Hospital of Yuhuan from February 2020 to May 2023. Patients were grouped using the envelope method. RESULTS: After treatment, the study group's treatment effective rate was 94.90% (46/49 patients), significantly higher than that in the control group (79.17%, 38/48 cases; P < 0.05). Before treatment, there was no difference in Constant Murley Score (CMS) scores, shoulder mobility, or 36-Item Short Form Health Survey (SF-36) scale scores (P > 0.05). Compared with those before treatment, the CMS scores (including pain, daily living ability, shoulder mobility, and muscle strength), all aspects of shoulder mobility (forward flexion, posterior extension, external rotation, internal rotation), and SF-36 scale scores (including physiological, psychological, emotional, physical, vitality, and health status) were higher in both groups after treatment and significantly higher in the study group (P < 0.05). There was no difference in the occurrence of complications between the two treatment groups (P > 0.05). CONCLUSION: Electroacupuncture combined with rehabilitation techniques has a good treatment effect on patients with rotator cuff injuries, helps accelerate the recovery of shoulder function, improves the quality of life, and is highly safe.

Attentional Bias for Opioids in Taiwanese Heavy Smokers with Chronic Noncancer Pain.

Background and Objectives: Attentional bias (AB) for addictive substances is a feature of attention found in individuals with substance misuse or diagnosed with substance use disorders. When AB exists, the attention of the addicted individual may be quickly oriented to cues related to the addictive substance or be maintained on these cues for a longer time. AB toward opioids was found in Western samples of smokers with chronic noncancer pain. The level of AB was dose-responsive. However, similar studies in the Taiwanese population are lacking. This study compared the patterns of AB for opioid analgesics in Taiwanese participants with chronic noncancer pain to that of individuals without pain. This study aimed to investigate if AB toward opioids is presented in Taiwanese heavy smokers who are on long-term opioid therapy for pain control. Materials and Methods: Participants were grouped into chronic noncancer pain smokers, chronic pain nonsmokers, and smokers without pain, according to smoking habits and whether or not on long-term opioid therapy for pain control. Each participant completed demographic questionnaires, mood scales, and the opioid-related visual probe task. Differences in AB among the groups were compared using a three-way analysis of covariance controlling for daily cigarette consumption. Results: Chronic noncancer pain smokers (n = 17) and chronic pain nonsmokers (n = 16) displayed more severe levels of depression, anxiety, and pain, compared to smokers without pain (n = 28). Only did chronic pain nonsmokers show significant AB for opioid cues that were displayed for a short time. Analysis on reaction time found that smokers without pain consistently responded faster to the tasks. No difference in reaction time was found between the pain groups. Conclusions: The current study did not fully replicate findings from studies that were based in Western countries. Formulary availability and regulatory limitations might have affected patient's perception of prescription opioids in Taiwan. However, chronic pain nonsmokers exhibited initial orientation toward opioid-related cues when daily cigarette consumption was accounted for. According to previous research, this AB for shortly displayed opioid cues can be associated with the expectation of pain relief. The current finding also indicated general psychomotor retardation in individuals who were on long-term use of opioids.

Efficacy of color Doppler ultrasound and contrast-enhanced ultrasound in identifying vascular invasion in pancreatic ductal adenocarcinoma.

OBJECTIVES: To compare color Doppler ultrasound and contrast-enhanced ultrasound (CEUS) in evaluating vascular invasion in pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: This retrospective study included 210 patients with PDAC who were evaluated by color Doppler ultrasound, CEUS, and contrast-enhanced computed tomography (CECT) at our institution between January 2017 and December 2020. Pathologic results were used as the gold standard in patients who underwent surgical and intraoperative exploration. For nonsurgical patients, CECT results were used as the reference standard. The vessels evaluated included those in the peripancreatic arterial system and venous system. The diagnostic performances of color Doppler ultrasound and CEUS for vascular invasion were compared. RESULTS: In 51 patients who underwent surgery and intraoperative exploration, color Doppler ultrasound and CEUS differed only in assessing venous system invasion in patients with PDAC of the pancreatic body and tail, with the former being superior to the latter. In 159 nonsurgical patients, there was no difference between CEUS and color Doppler ultrasound in assessing superior mesenteric arteriovenous invasion. CEUS was superior to color Doppler ultrasound in evaluating the celiac artery and its branches, with an accuracy of up to 97.8% for some vessels. Color Doppler ultrasound was ideal for evaluating the splenic and portal veins. CONCLUSION: CEUS is more suitable for the evaluation of peripancreatic arteries than color Doppler. CEUS combined with color Doppler ultrasound can be used as a potential supplement to CECT and is also expected to be used to evaluate vascular invasion of PDAC after chemotherapy. CRITICAL RELEVANCE STATEMENT: Contrast-enhanced US and color Doppler in the assessment of vascular invasion in pancreatic ductal adenocarcinoma have their respective advantages, through standardized ultrasound processes are expected to improve the efficiency of inspection. KEY POINTS: Contrast-enhanced US has unique advantages in assessing pancreatic ductal adenocarcinoma invasion of the celiac artery. Doppler imaging is of high value in assessing venous system invasion. Standardization of ultrasound imaging procedures for pancreatic ductal adenocarcinoma is expected to improve efficiency.

Interaction between ambient CO and temperature or relative humidity on the risk of stroke hospitalization.

Although the independent effects of ambient CO, temperature or humidity on stroke have been confirmed, it is still unclear where there is an interaction between these factors and who is sensitive populations for these. The stroke hospitalization and ambient CO, temperature, humidity data were collected in 22 Counties and districts of Ningxia, China in 2014-2019. The lagged effect of ambient CO, temperature or humidity were analyze by the generalized additive model; the interaction were evaluated by the bivariate response surface model and stratified analysis with relative excessive risk (RERI). High temperature and CO levels had synergistic effects on hemorrhagic stroke (RERI = 0.05, 95% CI 0.033-0.086) and ischemic stroke (RERI = 0.035, 95% CI 0.006-0.08). Low relative humidity and CO were synergistic in hemorrhagic stroke (RERI = 0.192, 95% CI 0.184-0.205) and only in ischemic stroke in the elderly group (RERI = 0.056, 95% CI 0.025-0.085). High relative humidity and CO exhibited antagonistic effects on the risk of ischemic stroke hospitalization in both male and female groups (RERI = - 0.088, 95% CI - 0.151to - 0.031; RERI = - 0.144, 95% CI - 0.216 to - 0.197). Exposure to CO increases the risk of hospitalization related to hemorrhagic and ischemic strokes. CO and temperature or humidity interact with risk of stroke hospitalization with sex and age differences.

Cardiovascular disease among bariatric surgery candidates: coronary artery screening and the impact of metabolic syndrome.

BACKGROUND: Obesity is known as a risk factor for cardiovascular disease (CVD). However, there is an absence of preoperative cardiac risk assessment in bariatric surgery candidates and the incidence of CVD among these high-risk patients is still unknown. METHODS: A consecutive series of bariatric surgery candidates at two Chinese tertiary hospitals received coronary CT angiography or coronary angiography from 2017 to 2023. Patients were categorized as metabolically unhealthy obesity (MUO) and metabolically healthy obesity (MHO) based on the presence or absence of MetS. CVD was diagnosed based on the maximum intraluminal stenosis > 1% in any of the segments of the major epicardial coronary arteries. Obstructive CVD was defined as coronary stenosis ≥ 50%. Binary multivariable logistic regression was performed to analyze the association between CVD and metabolic status. The number of principal MetS components was categorized into zero (without glycemic, lipid, and BP components), one (with one of the components), two (with any two components), and three (with all components) to explore their association with CVD. RESULTS: A total of 1446 patients were included in the study. The incidence of CVD and obstructive CVD were 31.7% and 9.6%. Compared with MHO patients, MUO patients had a significantly higher incidence of mild (13.7% vs. 6.1%, P < 0.05), moderate (7.4% vs. 0.8%, P < 0.05), and severe CVD (3.1% vs. 0%, P < 0.05). Following complete adjustment, compared with zero or one component, two principal MetS components was found to be associated with a notable increase in the risk of CVD (OR 2.05, 95% CI 1.18-3.58, P < 0.05); three principal MetS components were observed to have a higher risk of CVD and obstructive CVD (OR 2.68, 95% CI 1.56-4.62, P < 0.001; OR 3.93, 95% CI 1.19-12.93, P < 0.05). Each increase in the number of principal MetS components correlated with a 1.47-fold (95% CI 1.20-1.81, P < 0.001) and 1.78-fold (95% CI 1.24-2.55, P < 0.05) higher risk of CVD and obstructive CVD, respectively. CONCLUSION: This study reported the incidence of CVD based on multicenter bariatric surgery cohorts. CVD is highly prevalent in patients with obesity, especially in MUO patients. Increased number of principal MetS components will significantly elevate the risk of CVD.

Image features and clinical analysis of retroperitoneal pelvic schwannoma: a case report.

BACKGROUND: Schwannomas are benign usually encapsulated nerve sheath tumors derived from the Schwann cells, and affecting single or multiple nerves. The tumors commonly arise from the cranial nerves as acoustic neurinomas but they are extremely rare in the pelvis and the retroperitoneal area. Retroperitoneal pelvic schwannomas often present with non-specific symptoms leading to misdiagnosis and prolonged morbidity. CASE PRESENTATION: We report the case of a 59-year-old woman presenting with a feeling of heaviness in the lower abdomen who was found to have a retroperitoneal pelvic schwannoma originating from the right femoral nerve. She had a history of two resections of peripheral schwannomas at four different sites of limbs. After conducting magnetic resonance imaging, this pelvic schwannoma was misdiagnosed as a gynecological malignancy. The tumor was successfully removed by laparoscopic surgery. Pathological analysis of the mass revealed a benign schwannoma of the femoral nerve sheath with demonstrating strong, diffuse positivity for S-100 protein. CONCLUSIONS: Although retroperitoneal pelvic schwannoma is rare, it should be considered in the differential diagnosis of pelvic masses, especially in patients with a history of neurogenic mass or the presence of neurogenic mass elsewhere.

[Analysis of preoperative assessment of glandular mass in gynecomastia].

Objective: To investigate the effectiveness of axillary single-site laparoscopic subcutaneous mastectomy in treatment of gynecomastia (GYN) and the assessment method of glandular mass before operation. Methods: A clinical data of 65 GYN patients admitted between August 2023 and February 2024 and matched the selection criteria was retrospectively analyzed. The patients were (30.8±7.9) years old, with a body mass index (BMI) of 27.3 (24.9, 29.8) kg/m 2. According to Simon's grading criteria, the GYN was classified as gade Ⅰ in 8 cases, grade Ⅱa in 32 cases, grade Ⅱb in 21 cases, and grade Ⅲ in 4 cases. All patients underwent bilateral axillary single-site laparoscopic subcutaneous mastectomy. The operation time, intraoperative blood loss, postoperative bilateral extubation time, total length of hospital stay, and the occurrence of related complications were recorded. The cosmetic outcome score was assessed by questionnaire at 2 months after operation. Preoperative BMI, lying/standing sternal notch to nipple (SN-N), and lying/standing nipple to nipple (N-N) were measured. The differences in SN-N between standing and lying positions (ΔSN-N) and in N-N between lying and standing positions (ΔN-N) were calculated. The intraoperative resected glandular mass was recorded. The glandular mass-related indicators (BMI, ΔSN-N, ΔN-N) were compared between Simon grades. Spearman's correlation analysis and multiple linear regression analysis of glandular mass with BMI and ΔSN-N, ΔN-N and Simon grading (grades Ⅰ, Ⅱa, Ⅱb, and Ⅲ were assigned values of 1, 2, 3, and 4, respectively) of the corresponding side. Results: All operations were successfully completed with the operation time of 75.0 (60.0, 90.0) minutes, the intraoperative blood loss of 12.0 (11.0, 13.0) mL, and the bilateral extubation time of 1.5 (1.5, 1.5) days after operation. The total length of hospital stay was 3.0 (3.0, 3.0) days. Three cases of subcutaneous hematoma in the chest wall and 1 case of nipple areola numbness and discomfort occurred after operation, while the rest of the patients had no complication, such as postoperative haemorrhage, effusion, infection, and nipple areola necrosis. The subjective cosmetic scores were all 15 at 2 months after operation, which was very satisfactory. The differences in ΔSN-N of right side between Simon grade Ⅰ and grades Ⅱa, Ⅱb, Ⅲ and in ΔSN-N of left side between Simon grade Ⅰ and grades Ⅱb, Ⅲ were significant ( P<0.05), while the differences between the remaining grades were not significant ( P>0.05). The differences in ΔN-N between Simon grade Ⅱa and gradeⅡb and in BMI between Simon grade Ⅱb and grade Ⅲ were not significant ( P>0.05), while the differences between the remaining grades were significant ( P<0.05). The glandular masses of left and right breasts in 65 patients were 69.0 (52.1, 104.0) g and 73.0 (56.0, 94.0) g, respectively; and the difference between left and right breasts was not significant ( Z=-0.622, P=0.534). The data of the right breast was selected for correlation analysis. Correlation analysis showed that the right glandular mass was positive correlated with BMI and Simon grading, ΔSN-N, and ΔN-N ( P<0.05). Multiple linear regression analysis showed that Simon grading had a positive predictive effect on glandular mass, and the regression equation was as follows: right glandular mass=5.541+32.115×Simon grading ( R 2 =0.354, P<0.001). Conclusion: Axillary single-site laparoscopic subcutaneous mastectomy is an ideal surgical procedure for the treatment of GYN. BMI and Simon grading are closely related to GYN glandular mass, and have certain reference value for preoperative glandular mass assessment.

MARCH1 negatively regulates TBK1-mTOR signaling pathway by ubiquitinating TBK1.

BACKGROUND: TBK1 positively regulates the growth factor-mediated mTOR signaling pathway by phosphorylating mTOR. However, it remains unclear how the TBK1-mTOR signaling pathway is regulated. Considering that STING not only interacts with TBK1 but also with MARCH1, we speculated that MARCH1 might regulate the mTOR signaling pathway by targeting TBK1. The aim of this study was to determine whether MARCH1 regulates the mTOR signaling pathway by targeting TBK1. METHODS: The co-immunoprecipitation (Co-IP) assay was used to verify the interaction between MARCH1 with STING or TBK1. The ubiquitination of STING or TBK1 was analyzed using denatured co-immunoprecipitation. The level of proteins detected in the co-immunoprecipitation or denatured co-immunoprecipitation samples were determined by Western blotting. Stable knocked-down cells were constructed by infecting lentivirus bearing the related shRNA sequences. Scratch wound healing and clonogenic cell survival assays were used to detect the migration and proliferation of breast cancer cells. RESULTS: We showed that MARCH1 played an important role in growth factor-induced the TBK1- mTOR signaling pathway. MARCH1 overexpression attenuated the growth factor-induced activation of mTOR signaling pathway, whereas its deficiency resulted in the opposite effect. Mechanistically, MARCH1 interacted with and promoted the K63-linked ubiquitination of TBK1. This ubiquitination of TBK1 then attenuated its interaction with mTOR, thereby inhibiting the growth factor-induced mTOR signaling pathway. Importantly, faster proliferation induced by MARCH1 deficiency was weakened by mTOR, STING, or TBK1 inhibition. CONCLUSION: MARCH1 suppressed growth factors mediated the mTOR signaling pathway by targeting the STING-TBK1-mTOR axis.

[Study on optimal harvesting period and rational medicinal parts of Zanthoxylum nitidum based on statistics of main effective components].

To determine the optimal harvesting period and rational medicinal parts of Zanthoxylum nitidum, the main effective components of cultivated Z. nitidum samples, which originate from various growth years, harvesting months, and different parts were analyzed and compared with the wild samples. HPLC was performed on a Kinetex C18 column(4. 6 mm×100 mm, 2. 6 µm) with the gradient elution of 0. 3% phosphoric acid solution-acetonitrile(80 ∶ 20) containing 0. 2% triethylamine. The flow rate was 1. 0 m L·min-1, and the detection wavelength was 273 nm. The column temperature was 30 ℃. Nitidine chloride and chelerythrine, the main effective components, were determined as the markers. The results showed there was no significant difference in the contents of the main effective components among the roots of wild and cultivated Z. nitidum, as well as the roots and roots + stems of cultivated Z. nitidum. The statistical results of HCA and PCA indicated that the roots and stems could be clearly distinguished, but no distinction could be made between wild and cultivated products, which was consistent with the results of the significance analysis. The total contents of nitidine chloride and chelerythrine in roots and stems of Z. nitidum of 1-6 years old were 0. 114%-0. 256% and 0. 030%-0. 133%, respectively. These results suggested a positive correlation between the content of the main effective components and the growth years. No significant difference was observed between the contents of samples harvested in different seasons, indicating that the harvest season had no effect on the content of the main effective components of the Z. nitidum samples. The total contents of nitidine chloride and chelerythrine of the dried Z. nitidum samples(excluding branches) from three plantation bases were 0. 308%±0. 123% in Yunfu, 0. 192%±0. 025% in Maoming, and 0. 197%±0. 052% in Nanning, respectively, and they were all not less than 0. 15%, or in other words, the roots(including fibrous roots, taproots, and underground stems) and stems(aboveground stems) of Z. nitidum transplanted for more than 2. 5 years can meet the medical requirements. This study demonstrates that the cultivated Z. nitidum could be used as a valid substitute for the wild Z. nitidum, which provides a guarantee for the sustainable development and the application of Z. nitidum resources. The stems and roots could be considered medicinal parts of Z. nitidum. It is recommended to revise the medicinal parts of Z. nitidum to dried roots and stems in the next edition of Chinese Pharmacopoeia, and the medicinal parts can be harvested all year round. In order to ensure the content of effective components and clinical effectiveness, the root and stem should be harvested for medical use after the seedlings of Z. nitidum have been transplanted for more than three years.

The Relationship Between Static Characteristics of Physicians and Patient Consultation Volume in Internet Hospitals: Quantitative Analysis.

BACKGROUND: Internet medical treatment, also known as telemedicine, represents a paradigm shift in health care delivery. This contactless model allows patients to seek medical advice remotely, often before they physically visit a doctor's clinic. Herein, physicians are in a relatively passive position, as patients browse and choose their health care providers. Although a wealth of experience is undoubtedly a draw for many patients, it remains unclear which specific facets of a doctor's credentials and accomplishments patients prioritize during their selection process. OBJECTIVE: Our primary aim is to delve deeper into the correlation between physicians' static characteristics-such as their qualifications, experiences, and profiles on the internet-and the number of patient visits they receive. We seek to achieve this by analyzing comprehensive internet hospital data from public hospitals. Furthermore, we aim to offer insights into how doctors can present themselves more effectively on web-based platforms, thereby attracting more patients and improving overall patient satisfaction. METHODS: We retrospectively gathered web-based diagnosis and treatment data from the First Affiliated Hospital of Guangxi Medical University in 2023. These data underwent rigorous analysis, encompassing basic descriptive statistics, correlation analyses between key factors in doctors' internet-based introductions, and the number of patient consultation visits. Additionally, we conducted subgroup analyses to ascertain the independence of these vital factors. To further distill the essence from these data, we used nonnegative matrix factorization to identify crucial demographic characteristics that significantly impact patient choice. RESULTS: The statistical results suggested that there were significant differences in the distribution of consultation volume (P<.001), and the correlation analysis results suggested that there was a strong correlation between the two groups of data (ρ=0.93; P<.001). There was a correlation between the richness of a profile and popularity (P<.001). Patients were more interested in physicians with advanced titles, doctoral degrees, social activities, and scientific achievements (P<.001) as well as other institutional visit experiences (P=.003). More prosperous social activities, scientific achievements, experiences of other institutional visits, and awards were more common among people with advanced professional titles. Doctoral degrees remained attractive to patients when data were limited to senior physicians (P<.001). Patients trusted the medical staff with advanced titles, social activities, scientific achievements, and doctoral degrees (P<.001). CONCLUSIONS: Patient preferences for choosing a health care provider differed significantly between free and paid consultations. Notably, patients tended to trust doctors with advanced professional titles more and were more likely to seek out those with doctoral qualifications over other professional ranks. Additionally, physicians who actively participated in social events and scientific endeavors often had an advantage in attracting new patients. Given these insights, doctors who invest in enhancing their personal and professional experiences within these domains are likely to see increased popularity and patient satisfaction.

Structural variant landscapes reveal convergent signatures of evolution in sheep and goats.

BACKGROUND: Sheep and goats have undergone domestication and improvement to produce similar phenotypes, which have been greatly impacted by structural variants (SVs). Here, we report a high-quality chromosome-level reference genome of Asiatic mouflon, and implement a comprehensive analysis of SVs in 897 genomes of worldwide wild and domestic populations of sheep and goats to reveal genetic signatures underlying convergent evolution. RESULTS: We characterize the SV landscapes in terms of genetic diversity, chromosomal distribution and their links with genes, QTLs and transposable elements, and examine their impacts on regulatory elements. We identify several novel SVs and annotate corresponding genes (e.g., BMPR1B, BMPR2, RALYL, COL21A1, and LRP1B) associated with important production traits such as fertility, meat and milk production, and wool/hair fineness. We detect signatures of selection involving the parallel evolution of orthologous SV-associated genes during domestication, local environmental adaptation, and improvement. In particular, we find that fecundity traits experienced convergent selection targeting the gene BMPR1B, with the DEL00067921 deletion explaining ~10.4% of the phenotypic variation observed in goats. CONCLUSIONS: Our results provide new insights into the convergent evolution of SVs and serve as a rich resource for the future improvement of sheep, goats, and related livestock.

Enantioselective formal total synthesis of dihydrospirotryprostatin B.

Spirotryprostatins are representative members of medicinally interesting bioactive molecules of the spirooxindole natural products. In this communication, we present a novel enantioselective total synthesis of the spirooxindole alkaloid dihydrospirotryprostatin B. The synthesis takes advantage of copper-catalyzed tandem reaction of o-iodoanilide chiral sulfinamide derivatives with alkynone to rapidly construct the key quaternary carbon stereocenter of the natural product dihydrospirotryprostatin B.

Tanreqing Injection Inhibits Activation of NLRP3 Inflammasome in Macrophages Infected with Influenza A Virus by Promoting Mitophagy.

OBJECTIVE: To investigate the inhibitory effect of Tanreqing Injection (TRQ) on the activation of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome in macrophages infected with influenza A virus and the underlying mechanism based on mitophagy pathway. METHODS: The inflammatory model of murine macrophage J774A.1 induced by influenza A virus [strain A/Puerto Rico/8/1934 (H1N1), PR8] was constructed and treated by TRQ, while the mitochondria-targeted antioxidant Mito-TEMPO and autophagy specific inhibitor 3-methyladenine (3-MA) were used as controls to intensively study the anti-inflammatory mechanism of TRQ based on mitophagy-mitochondrial reactive oxygen species (mtROS)-NLRP3 inflammasome pathway. The levels of NLRP3, Caspase-1 p20, microtubule-associated protein 1 light chain 3 II (LC3II) and P62 proteins were measured by Western blot. The release of interleukin-1ß (IL-1ß) was tested by enzyme linked immunosorbent assay, the mtROS level was detected by flow cytometry, and the immunofluorescence and co-localization of LC3 and mitochondria were observed under confocal laser scanning microscopy. RESULTS: Similar to the effect of Mito-TEMPO and contrary to the results of 3-MA treatment, TRQ could significantly reduce the expressions of NLRP3, Caspase-1 p20, and autophagy adaptor P62, promote the expression of autophagy marker LC3II, enhance the mitochondrial fluorescence intensity, and inhibit the release of mtROS and IL-1ß (all P<0.01). Moreover, LC3 was co-localized with mitochondria, confirming the type of mitophagy. CONCLUSION: TRQ could reduce the level of mtROS by promoting mitophagy in macrophages infected with influenza A virus, thus inhibiting the activation of NLRP3 inflammasome and the release of IL-1ß, and attenuating the inflammatory response.

Multimodal training with dual-task enhances immediate and retained effects on dual-task effects of gait speed not by cognitive-motor trade-offs in stroke survivors: a randomized controlled trial.

PURPOSE: Individuals who have experienced stroke may benefit from dual-task related training to improve gait speed performance. Whether noted improvements reflect true effects on gait or cognitive-motor trade-offs still remains unclear. Therefore, this study aimed to investigate the effects of dual-task training on dual-task effects of both walking and cognitive domains in stroke survivors. MATERIALS AND METHODS: Forty-four individuals with stroke were randomized to dual-task or single-task training groups. Both groups exercised three 60-minute sessions per week for 4 weeks. The primary outcomes were dual-task effects on gait speed and cognitive score. Outcomes were assessed before and after the intervention and 1-month follow-up. RESULTS: While both groups exhibited improvement in absolute gait speed under dual-task conditions, the dual-task training group demonstrated superior results by providing an additional gain on dual-task effects of gait speed. Compared to single-task training, dual-task training exhibited a significant improvement in dual-task effects of gait speed at post-treatment and follow-up. Regarding the dual-task effects on cognitive scores, no significant differences within and between groups after training were observed. CONCLUSION: Dual-task training enhances immediate and retained effects on the dual-task effects of gait speed in individuals with stroke, not by cognitive-motor trade-offs. TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. CLINICALTRIALS.GOV IDENTIFIER: NCT02686515.

Dual-task interference during walking has important consequences for stroke survivors to walk safely.Multimodal training with dual-task enhances immediate and retained effects on the dual-task effects of gait speed in individuals with stroke, not by cognitive-motor trade-offs.Clinicians are encouraged to incorporate multimodal training with dual-task into the exercise routines to enhance walking under dual-task conditions in stroke survivors.

A time-resolved multi-omics atlas of transcriptional regulation in response to high-altitude hypoxia across whole-body tissues.

High-altitude hypoxia acclimatization requires whole-body physiological regulation in highland immigrants, but the underlying genetic mechanism has not been clarified. Here we use sheep as an animal model for low-to-high altitude translocation. We generate multi-omics data including whole-genome sequences, time-resolved bulk RNA-Seq, ATAC-Seq and single-cell RNA-Seq from multiple tissues as well as phenotypic data from 20 bio-indicators. We characterize transcriptional changes of all genes in each tissue, and examine multi-tissue temporal dynamics and transcriptional interactions among genes. Particularly, we identify critical functional genes regulating the short response to hypoxia in each tissue (e.g., PARG in the cerebellum and HMOX1 in the colon). We further identify TAD-constrained cis-regulatory elements, which suppress the transcriptional activity of most genes under hypoxia. Phenotypic and transcriptional evidence indicate that antenatal hypoxia could improve hypoxia tolerance in offspring. Furthermore, we provide time-series expression data of candidate genes associated with human mountain sickness (e.g., BMPR2) and high-altitude adaptation (e.g., HIF1A). Our study provides valuable resources and insights for future hypoxia-related studies in mammals.

Primulaweiliei (Primulaceae), a new species from Hubei, Central China.

In this study, we describe and illustrate a new species, Primulaweiliei L.S.Yang, Z.K.Wu & G.W.Hu, from the Shennongjia Forestry District, Hubei Province in Central China. It is morphologically assigned to Primulasect.Aleuritia based on its dwarf and hairless habit, long petiole, fruits longer than calyx and covered by farina on the scape. This new species is similar to P.gemmifera and P.munroisubsp.yargongensis in the same section, but it can be distinguished by its smaller calyxes, homostylous flowers, corolla tube throat without annular appendage and only 1-2 flowers in each inflorescence. Based on the assessment conducted according to the IUCN Red List criteria, we propose that P.weiliei be classified as a Critically Endangered (CR) species.