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Abstract Microfluidic-engineered hydrogel microspheres have emerged as a promising avenue for advancements in tissue engineering and regenerative medicine, particularly through the precise manipulation of fluids to achieve personalized composite biomaterials. In this study, we employed microfluidic technology to fabricate hydrogel microspheres (HMs) using Chinese herbal Bletilla striata polysaccharide (BSP) as the primary material. Concurrently, the natural active ingredient 20(S)-protopanaxadiol (PPD) was encapsulated within the HMs in the form of liposomes (PPD-Lipo), resulting in the formation of nanocomposite hydrogel microspheres (PPD-Lipo@HMs) intended for diabetic wound tissue repair. PPD-Lipo@HMs are characterized by the expansive specific surface area, adjustable mechanical properties, and exceptional biocompatibility. PPD-Lipo@HMs can stimulate the production of vascular endothelial factors, which in turn enhances the migration of endothelial cells, the creation of tubes, angiogenesis, and tissue repair. Moreover, the PPD-Lipo@HMs accumulation produces a microsphere scaffold that effectively covers damaged tissues, promoting the attachment, spread, and multiplication of fibroblast and endothelial cells. The polysaccharide material BSP within PPD-Lipo@HMs can modulate the immune microenvironment of the damaged tissue, reducing inflammation, encouraging re-epithelialization and granulation tissue formation, accelerating angiogenesis and collagen deposition, ultimately leading to tissue repair. The findings highlight the superior therapeutic efficacy of the microfluidic-engineered PPD-Lipo@HMs in addressing the complex challenges of diabetic wound tissue repair, thereby affirming the significant potential of microfluidic engineering technology in tissue repair applications.

Background: The long-term effects of extracorporeal shockwave therapy (ESWT) on rotator cuff repair are unknown. Objectives: To investigate the functional outcomes and structural changes of ESWT at 3-year follow-up after rotator cuff repair. Methods: A randomized clinical trial was conducted, including patients who underwent rotator cuff repair. The patients were assigned to two groups based on whether they underwent radial ESWT 3 months postoperatively. The ESWT Group received 5 weeks of rehabilitation and ESWT weekly, whereas the CONTROL Group received only rehabilitation. Visual analog scale (VAS) pain score and functional scores were analyzed at 3 months (baseline), 6 months, and 3 years follow-up. In addition, MRI and ultrasonography were used to assess tendon maturation, integrity, tendon quality, acromiohumeral distance (AHD), and muscle fatty infiltration. Results: Finally, 32 participants completed all the assessments. At the final follow-up, 2 patients in the ESWT Group (16.5 %) versus one patient in the CONTROL Group (6.25 %) had rotator cuff failure (P = 0.176). The ESWT treatment showed similar clinical outcomes in VAS-pain score, functional scores, tendon quality, AHD, and muscle fatty infiltration versus the CONTROL Group (Ps > 0.05). MRI analysis indicated improved tendon healing after ESWT treatment at both 6-month (P = 0.036) and 3-year follow-up (P = 0.028). Conclusion: Early intervention with radial ESWT sustained long-term effects on the healing of the repaired rotator cuff and similar functional outcomes at long-term follow-up compared with standard rehabilitation.

Abstract Background Lodging, a crucial agronomic trait linked to soybean yield, poses a significant challenge in soybean production. Nevertheless, there has been less research on soybean lodging compared to other important agronomic traits, hindering progress in breeding high-yield soybeans. Our goals were to investigate lodging, pinpoint quantitative trait loci (QTL) linked to lodging, and forecast potential candidate genes linked to this trait. To achieve this, we employed a recombinant inbred line (RIL) population derived from a cross between Guizao 1 and B13 (GB) across various environments. Results The lodging score of the RIL population was found to be significantly positively correlated with flowering time, maturity time, plant height, number of main stem nodes, stem diameter, and internode length, with correlation coefficients ranging from 0.457 to 0.783. A total of 84 QTLs associated with soybean lodging and related traits were identified using the GB population. The contribution of phenotypic variance ranged from 1.26 to 66.87%, with LOD scores ranging from 2.52 to 69.22. Additionally, within these QTLs, a stable major QTL associated with lodging was newly discovered in the GB population. Out of the ten major QTLs associated with other related traits, nine of them were situated within the qLD-4-1 interval of the major lodging score locus, displaying phenotypic variations ranging from 12.10 to 66.87%. Specific alterations in gene expression were revealed through the analysis of resequencing data from the two parental lines, potentially indicating their significant roles in lodging. Subsequently, it was determined through qRT-PCR that four genes are likely to be the major genes controlling soybean lodging. Conclusions This study’s findings offer valuable insights into the genetic underpinnings of soybean lodging resistance traits. By comprehending the potential genetic factors associated with lodging, this research lays the groundwork for breeding high-yield soybeans with improved lodging resistance.

Background: In the recent decade, there has been substantial progress in the technologies and philosophies associated with diagnosing and treating anterior cruciate ligament (ACL) injuries in China. The therapeutic efficacy of ACL reconstruction in re-establishing the stability of the knee joint has garnered widespread acknowledgment. However, the path toward standardizing diagnostic and treatment protocols remains to be further developed and refined. Objective: In this context, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) collaboratively developed an expert consensus on diagnosing and treating ACL injury, aiming to enhance medical quality through refining professional standards. Methods: The consensus drafting team invited experts across the Greater China region, including the mainland, Hong Kong, Macau, and Taiwan, to formulate and review the consensus using a modified Delphi method as a standardization approach. As members of the CSSM Lower Limb Study Group and the CAOS Arthroscopy and Sports Medicine Study Group, invited experts concentrated on two pivotal issues: “Graft Selection” and “Clinical Outcome Evaluation” during the second part of the consensus development. Results: This focused discussion ultimately led to a strong consensus on nine specific consensus terms. Conclusion: The consensus clearly states that ACL reconstruction has no definitive “gold standard” graft choice. Autografts have advantages in healing capability but are limited in availability and have potential donor site morbidities; allografts reduce surgical trauma but incur additional costs, and there are concerns about slow healing, quality control issues, and a higher failure rate in young athletes; synthetic ligaments allow for early rehabilitation and fast return to sport, but the surgery is technically demanding and incurs additional costs. When choosing a graft, one should comprehensively consider the graft's characteristics, the doctor's technical ability, and the patient's needs. When evaluating clinical outcomes, it is essential to ensure an adequate sample size and follow-up rate, and the research should include patient subjective scoring, joint function and stability, complications, surgical failure, and the return to sport results. Medium and long-term follow-ups should not overlook the assessment of knee osteoarthritis.

Background: Research on return to sport and psychological recovery in anterior cruciate ligament (ACL) revision remains scarce. The clinical efficacy of artificial ligament in ACL revision requires further exploration. Our objectives were (1) to compare the midterm clinical outcomes of artificial ligament versus allogenic tendon graft in ACL revision and (2) to analyze the effects of employing artificial ligament on return to sport and psychological recovery in ACL revision. Methods: This cohort study included the cases receiving ACL revision from 2014 to 2021 in Sports Medicine Department of Huashan Hospital. The grafts used were Ligament Advanced Reinforcement System (LARS) and ATT allograft. We recorded patients' baseline data. The final follow-up assessment included subjective scales, physical examination, and return to sport status. We recorded the rates and timings of return to sport. Subjective scales included the 2000 International Knee Documentation Committee (IKDC) subjective score, Lysholm Knee Scaling Score (LKSS), Knee injury and Osteoarthritis Outcome Score (KOOS), Tegner activity score, Marx activity rating score, and Anterior Cruciate Ligament-Return to Sport after Injury (ACL-RSI). Anterior knee stability was assessed using the KT-1000 arthrometer. Results: Fifty cases (LARS group: 27; ATT group: 23) enrolled and 45 (LARS group: 23; ATT group: 22) completed evaluations with a median follow-up period of 49 months. At recent follow-up, LARS group outperformed in knee stability (1.0 ± 1.9 mm vs. 2.6 ± 3.0 mm, P = 0.039), confidence (86.7 ± 12.4 vs. 69.4 ± 18.6, P

Introduction: Acute lung injury (ALI) is a lung disease characterized by inflammation and still requires further drug development. Forsythiaside A as the active compound of Forsythiae Fructus has the therapeutic potential for ALI. Objective: To investigate the mechanism of forsythiaside A in treating ALI through PPAR-γ and its conjugate RXR-α based on gut-lung axis. Methods: This study constructed in vitro and in vivo injury models using LPS and TNF-α. Forsythiaside A was used for the drug treatment, and RXR-α inhibitor UVI3003 was used to interfere with PPAR-γ/RXR-α complexes in the cells. HE staining was used for histopathological examination. Serum endotoxin contents were determined using limulus lysate kit. IHC staining and Western blot were conducted to assess the protein expressions. ELISA was applied to examine the content of pro-inflammatory cytokines in the cell supernatants. The protein interactions were analyzed via CO-IP. Results: In vivo results showed that forsythiaside A regulated PPAR-γ/RXR-α and inhibited TLR4/MAPK/NF-κB and MLCK/MLC2 signal pathways, thus inhibiting inflammation and epithelial barrier damages of lung and colon in ALI mice induced by intratracheal LPS. PPAR-γ/RXR-α were promoted by forsythiaside A in lungs, whereas inhibited by forsythiaside A in colons. Additionally, in vitro results showed that forsythiaside A suppressed inflammation and epithelial barrier damages in macrophages and lung/colon epithelial cells, by manipulating PPAR-γ/RXR-α to suppress the LPS- and TNF-α-induced activation of TLR4/MAPK/NF-κB and NF-κB/MLCK/MLC2 signal pathways. Moreover, further mechanism study indicated that forsythiaside A showed a cell-specific regulatory effect on PPAR-γ/RXR-α complex. Specifically, the PPAR-γ/RXR-α protein interactions were promoted by forsythiaside A in LPS-induced macrophages RAW264.7 and TNF-α-induced lung epithelial cells A549, but inhibited by forsythiaside A in TNF-α-induced colon epithelial cells SW620. Conclusion: In the treatment of ALI, Forsythiaside A inhibited inflammation and epithelial barrier damages of lung and colon through its regulation on PPAR-γ/RXR-α complex.

Abstract The isotopic composition has long been used to investigate the factors influencing precipitation, whereas the variations of event-based precipitation isotopes caused by moisture transition and synoptic meteorological conditions remain limited. Here we present triple oxygen and hydrogen isotopes in event-based precipitation during West China Autumn Precipitation to evaluate the influence of various moisture sources in the hydrological process. Isotopes δ18O, δ17O, and δD peak with convective precipitation at the onset stage, then drop to their lowest amid stratiform precipitation during the middle stage, and rise again towards the end. In contrast, Δ′17O levels remain elevated throughout the mid-stage of West China Autumn Precipitation compared to the onset and end stages. These isotopic variations, coupled with moisture analysis, reveal a distinct moisture source transition from the West Pacific Ocean to the westerly domain during West China Autumn Precipitation accompanied by the retreat of the Asian summer monsoon from Northwest China.

Neuropathic pain (NP) is a common, intractable chronic pain caused by nerve dysfunction and primary lesion of the nervous system. The etiology and pathogenesis of NP have not yet been clarified, so there is a lack of precise and effective clinical treatments. In recent years, traditional Chinese medicine (TCM) has shown increasing advantages in alleviating NP. Our review aimed to define the therapeutic effect of TCM (including TCM prescriptions, TCM extracts and natural products from TCM) on NP and reveal the underlying mechanisms. Literature from 2018 to 2024 was collected from databases including Web of Science, PubMed, ScienceDirect, Google academic and CNKI databases. Herbal medicine, Traditional Chinese medicines (TCM), neuropathic pain, neuralgia and peripheral neuropathy were used as the search terms. The anti-NP activity of TCM is clarified to propose strategies for discovering active compounds against NP, and provide reference to screen anti-NP drugs from TCM. We concluded that TCM has the characteristics of multi-level, multi-component, multi-target and multi-pathway, which can alleviate NP through various pathways such as anti-inflammation, anti-oxidant, anti-apoptotic pathway, regulating autophagy, regulating intestinal flora, and influencing ion channels. Based on the experimental study and anti-NP mechanism of TCM, this paper can offer analytical evidence to support the effectiveness in treating NP. These references will be helpful to the research and development of innovative TCM with multiple levels and multiple targets. TCM can be an effective treatment for NP and can serve as a treasure house for new drug development.

As the COVID-19 pandemic has progressed, increasing evidences suggest that the gut microbiota may play a crucial role in the effectiveness of SARS-CoV-2 vaccine. Thus, this study was aimed at investigating the influence of SARS-CoV-2 vaccine on the gut microbiota and short-chain fatty acids (SCFAs) of organisms exposed to environmental contaminants, i.e., plasticizers: phthalate esters. We found that in mice, exposure to dioctyl terephthalate (DOTP) and bis −2-ethylhexyl phthalate (DEHP) decreased the blood glucose level and white fat weight, induced inflammatory responses, caused damage to liver and intestinal tissues, and disrupted the gut microbiota composition and SCFAs metabolism. Specifically, the Bacteroidetes phylum was positively correlated with BBIBP-CorV vaccine, while acetic acid was negatively associated with the vaccine. Interestingly, the BBIBP-CorV vaccine somewhat alleviated tissue inflammation and reduced the contents of acetic acid and propionic acid in mice exposed to DEHP and DOTP. These findings were confirmed by a fecal microbiota transplantation assay. Overall, this study revealed that exposure to DEHP and DOTP adversely affects the gut microbiota and SCFAs, while the BBIBP-CorV vaccine can protect mice against these effects. This work highlighted the relationship between BBIBP-CorV vaccination, gut microbiome composition, and responses to plasticizers, which may facilitate the development and risk assessment of SARS-CoV-2 vaccines and environmental contaminants on microbiota health.

Hepatic subcapsular hematoma (HSH) is an uncommon complication of pregnancy and is associated with elevated rates of maternal and foetal mortality. The rupture of an HSH is a critical situation that necessitates immediate and timely intervention to prevent loss of life. We present here, a case of a spontaneously ruptured massive HSH caused by preeclampsia. In addition, we conducted a comprehensive review of existing literature, encompassing 49 cases of HSH associated with pregnancy. If a pregnant woman with gestational hypertension experiences right upper abdominal pain with shoulder pain or radiating shoulder pain, it is crucial for her to have an urgent abdominal ultrasound because of the potential development of HSH and/or rupture. Our review of current literature suggests that opting for a caesarean section may offer notable advantages in preventing HSH rupture.

Abstract Determining the precise course of bacterial infection requires abundant in vivo real‐time data. Synchronous monitoring of the bacterial load, temperature, and immune response can satisfy the shortage of real‐time in vivo data. Here, we conducted a study in the joint‐infected mouse model to synchronously monitor the bacterial load, temperature, and immune response using the second near‐infrared (NIR‐II) fluorescence imaging, infrared thermography, and immune response analysis for 2 weeks. Staphylococcus aureus (S. aureus) was proved successfully labeled with glucose‐conjugated quantum dots in vitro and in subcutaneous‐infected model. The bacterial load indicated by NIR‐II fluorescence imaging underwent a sharp drop at 1 day postinfection. At the same time, the temperature gap detected through infrared thermography synchronously brought by infection reached lowest value. Meanwhile, the flow cytometry analysis demonstrated that immune response including macrophage, neutrophil, B lymphocyte, and T lymphocyte increased to the peak at 1 day postinfection. Moreover, both M1 macrophage and M2 macrophage in the blood have an obvious change at ~ 1 day postinfection, and the change was opposite. In summary, this study not only obtained real‐time and long‐time in vivo data on the bacterial load, temperature gap, and immune response in the mice model of S. aureus infection, but also found that 1 day postinfection was the key time point during immune response against S. aureus infection. Our study will contribute to synchronously and precisely studying the complicated complex dynamic relationship after bacterial infection at the animal level.

Abstract Background Functional connectivity (FC) biomarkers play a crucial role in the early diagnosis and mechanistic study of Alzheimer’s disease (AD). However, the identification of effective FC biomarkers remains challenging. In this study, we introduce a novel approach, the spatiotemporal graph convolutional network (ST-GCN) combined with the gradient-based class activation mapping (Grad-CAM) model (STGC-GCAM), to effectively identify FC biomarkers for AD. Methods This multi-center cross-racial retrospective study involved 2,272 participants, including 1,105 cognitively normal (CN) subjects, 790 mild cognitive impairment (MCI) individuals, and 377 AD patients. All participants underwent functional magnetic resonance imaging (fMRI) and T1-weighted MRI scans. In this study, firstly, we optimized the STGC-GCAM model to enhance classification accuracy. Secondly, we identified novel AD-associated biomarkers using the optimized model. Thirdly, we validated the imaging biomarkers using Kaplan–Meier analysis. Lastly, we performed correlation analysis and causal mediation analysis to confirm the physiological significance of the identified biomarkers. Results The STGC-GCAM model demonstrated great classification performance (The average area under the curve (AUC) values for different categories were: CN vs MCI = 0.98, CN vs AD = 0.95, MCI vs AD = 0.96, stable MCI vs progressive MCI = 0.79). Notably, the model identified specific brain regions, including the sensorimotor network (SMN), visual network (VN), and default mode network (DMN), as key differentiators between patients and CN individuals. These brain regions exhibited significant associations with the severity of cognitive impairment (p

Skeletal muscle has a robust regeneration ability that is impaired by severe injury, disease, and aging, resulting in a decline in skeletal muscle function. Therefore, improving skeletal muscle regeneration is a key challenge in treating skeletal muscle-related disorders. Owing to their significant role in tissue regeneration, implantation of M2 macrophages (M2Mø) has great potential for improving skeletal muscle regeneration. Here, we present a short-wave infrared (SWIR) fluorescence imaging technique to obtain more in vivo information for an in-depth evaluation of the skeletal muscle regeneration effect after M2Mø transplantation. SWIR fluorescence imaging was employed to track implanted M2Mø in the injured skeletal muscle of mouse models. It is found that the implanted M2Mø accumulated at the injury site for two weeks. Then, SWIR fluorescence imaging of blood vessels showed that M2Mø implantation could improve the relative perfusion ratio on day 5 (1.09 ± 0.09 vs 0.85 ± 0.05; p = 0.01) and day 9 (1.38 ± 0.16 vs 0.95 ± 0.03; p = 0.01) post-injury, as well as augment the degree of skeletal muscle regeneration on day 13 post-injury. Finally, multiple linear regression analyses determined that post-injury time and relative perfusion ratio could be used as predictive indicators to evaluate skeletal muscle regeneration. These results provide more in vivo details about M2Mø in skeletal muscle regeneration and confirm that M2Mø could promote angiogenesis and improve the degree of skeletal muscle repair, which will guide the research and development of M2Mø implantation to improve skeletal muscle regeneration.

Abstract Alzheimer's disease (AD) constitutes a neurodegenerative disorder marked by a progressive decline in cognitive function and memory capacity. The accurate diagnosis of this condition predominantly relies on cerebrospinal fluid (CSF) markers, notwithstanding the associated burdens of pain and substantial financial costs endured by patients. This study encompasses subjects exhibiting varying degrees of cognitive impairment, encompassing individuals with subjective cognitive decline, mild cognitive impairment, and dementia, constituting a total sample size of 82 participants. The primary objective of this investigation is to explore the relationships among brain atrophy measurements derived from magnetic resonance imaging, atypical electroencephalography (EEG) patterns, behavioral assessment scales, and amyloid β‐protein (Aβ) indicators. The findings of this research reveal that individuals displaying reduced Aβ1‐42/Aβ‐40 levels exhibit significant atrophy in the frontotemporal lobe, alongside irregularities in various parameters related to EEG frequency characteristics, signal complexity, inter‐regional information exchange, and microstates. The study additionally endeavors to estimate Aβ1‐42/Aβ‐40 content through the application of a random forest algorithm, amalgamating structural data, electrophysiological features, and clinical scales, achieving a remarkable predictive precision of 91.6%. In summary, this study proposes a cost‐effective methodology for acquiring CSF markers, thereby offering a valuable tool for the early detection of AD.

Abstract Background Many studies have investigated how nanoplastics (NPs) exposure mediates nerve and intestinal toxicity through a dysregulated brain-gut axis interaction, but there are few studies aimed at alleviating those effects. To determine whether and how vitamin D can impact that toxicity, fish were supplemented with a vitamin D-low diet and vitamin D-high diet. Results Transmission electron microscopy (TEM) showed that polystyrene nanoplastics (PS-NPs) accumulated in zebrafish brain and intestine, resulting in brain blood–brain barrier basement membrane damage and the vacuolization of intestinal goblet cells and mitochondria. A high concentration of vitamin D reduced the accumulation of PS-NPs in zebrafish brain tissues by 20% and intestinal tissues by 58.8% and 52.2%, respectively, and alleviated the pathological damage induced by PS-NPs. Adequate vitamin D significantly increased the content of serotonin (5-HT) and reduced the anxiety-like behavior of zebrafish caused by PS-NPs exposure. Virus metagenome showed that PS-NPs exposure affected the composition and abundance of zebrafish intestinal viruses. Differentially expressed viruses in the vitamin D-low and vitamin D-high group affected the secretion of brain neurotransmitters in zebrafish. Virus AF191073 was negatively correlated with neurotransmitter 5-HT, whereas KT319643 was positively correlated with malondialdehyde (MDA) content and the expression of cytochrome 1a1 (cyp1a1) and cytochrome 1b1 (cyp1b1) in the intestine. This suggests that AF191073 and KT319643 may be key viruses that mediate the vitamin D reduction in neurotoxicity and immunotoxicity induced by PS-NPs. Conclusion Vitamin D can alleviate neurotoxicity and immunotoxicity induced by PS-NPs exposure by directionally altering the gut virome. These findings highlight the potential of vitamin D to alleviate the brain-gut-virome disorder caused by PS-NPs exposure and suggest potential therapeutic strategies to reduce the risk of NPs toxicity in aquaculture, that is, adding adequate vitamin D to diet. Video Abstract

Abstract Background Compared to that of bacteria, the role of gut fungi in obesity development remains unknown. Results Here, alterations in gut fungal biodiversity and composition were confirmed in obese pig models and high-fat diet (HFD)-fed mice. Antifungal drugs improved diet-induced obesity, while fungal reconstruction by cohousing or fecal microbiota transplantation maintained the obese phenotype in HFD-fed mice. Fungal profiling identified 5 fungal species associated with obesity. Specifically, Ascomycota_sp. and Microascaceae_sp. were reduced in obese mice and negatively correlated with fat content. Oral supplementation with fungi was sufficient to prevent and treat diet-induced obesity. Clec7a, which is involved in fungal recognition, was highly expressed in HFD-fed mice. The Clec7a agonist accelerated diet-induced obesity, while Clec7a deficieny in mice resulted in resistance to diet-induced obesity and blocked the anti-obese effect of antifungal drugs and fungi. Conclusions Taken together, these results indicate that gut fungi/Clec7a signaling is involved in diet-induced obesity and may have therapeutic implications as a biomarker for metabolic dysregulation in humans. Video Abstract

Background: The treatment for Achilles tendinopathy varies widely, and there is no consensus regarding the optimal treatment for both non-insertional and insertional Achilles tendinopathy. The purpose of this study was to evaluate the clinical efficacy of extracorporeal shock wave therapy (ESWT) in the treatment of insertional and non-insertional Achilles tendinopathy (AT). Methods: Sixty patients with AT were invited to participate in this study. Patients were allocated to one of two groups according to the site of the AT, including an insertional AT (IAT) group and a non-insertional AT (NIAT) group. ESWT was performed once a week for five weeks for both groups. The Victorian Institute of Sport Assessment-Achilles questionnaire (VISA-A) score and the visual analog scale (VAS) were used five times to evaluate the clinical outcomes, including before treatment, immediately after treatment, as well as one month, three months, and five years after treatment. Results: At three months after treatment, the IAT group exhibited a significantly higher VISA-A score (82 ± 6 vs. 76 ± 11; p = 0.01) and a significantly lower VAS score (1 ± 1 vs. 2 ± 1; p

Objective: Blood supply to the meniscus determines its recovery and is a reference for treatment planning. This studyaimed to apply tissue clearing and three-dimensional (3D) imaging in exploring the quantitative distribution of bloodvessels in the mouse meniscus.Materials and Methods: In this experimental study, tissue clearing was performed to treat the bilateral knee joints oftransgenic mice with fluorescent vascular endothelial cells. Images were acquired using a light sheet microscope andthe vascular endothelial cells in the meniscus was analysed using 3D imaging. Quantitative methods were employedto further analyse the blood vessel distribution in the mouse meniscus.Results: The traditional three-equal-width division of the meniscus is as follows: the outer one-third is the red-red zone(RR), the inner one-third is the white-white zone (WW), and the transition area is the red-white zone (RW). The divisionrevealed significant signal differences between the RW and WW (P

Background. There is still no consensus on the treatment of frozen shoulder (FS). Clinical studies on extracorporeal shockwave therapy (ESWT) combined with arthroscopic capsular release (ACR) for FS are still lacking. Objectives. To investigate the effect of ESWT on short-term functional recovery after arthroscopic capsular release (ACR). Methods. A randomized clinical trial including 49 patients who under ACR was included. The patients were assigned to the ESWT group (n = 24) or non-ESWT group (n = 25) 2 weeks after surgery. Routine advanced rehabilitation program are given to all participants, while the ESWT group additionally received 5 times shockwave therapy. Visual analog scale (VAS) pain score, Constant score, University of California Los Angeles score (UCLA), UCLA-satisfaction, and shoulder range of motion (ROM) in four directions of flexion, abduction, internal, and external rotation were analyzed at the baseline (2 weeks postsurgery), 2 weeks, 8 weeks, and 12 weeks of follow-up. Repeated measure ANOVA is used to analyze the above outcomes. Results. A total of 46 participants completed all assessments. Pain and function improved in both groups. Comparing between the groups, we found that lower VAS pain scores and higher internal rotation were found in the ESWT group at each follow-up stage (all P0.05, 12 weeks Constant 95% CI: [ESWT: 82.98-92.94, non-ESWT: 78.24–88.20]). Conclusion. Extracorporeal shockwave therapy has a good analgesic effect and improves internal rotation after arthroscopic capsular release through short-term follow-up.

Proxy records of the oxygen isotope ratio of 18O/16O of past precipitation (δ18Op) have played an important role in revealing past hydroclimatic changes, on the basis of global observed relationships between monthly precipitation δ18Op and both precipitation amount and temperature only of a few years as reported by Dansgaard in 1964. It is therefore crucial to systematically re-evaluate the relationships using modern instrumental data. We analysed monthly and annual mean correlations from 108 global stations over the past about 60 years. Consistent with previously reported results, monthly δ18Op values in the high latitudes (≥60°) show a significant positive correlation with temperature (referred to as ‘temperature effect’) and a negative trend with precipitation amount in the low latitudes (≤20°) (‘amount effect’). However, these correlations do not hold true for yearly mean data for more than three-quarters of the stations evaluated. This indicates that the relationships between the different temporal resolutions could be more complicated than previously thought. For the related natural archives, such as ice cores, sediments, and carbonates, further careful evaluation is required to establish the robustness of their paleoclimatic implications. HIGHLIGHTS 108 GNIP stations were collected to re-analyse the relationships between δ18Op and climate variables on monthly and interannual timescales.; The relationships between δ18Op and climate variables varied on monthly and interannual timescales.; The results implied that the change of precipitation isotopic values may not be dominated by local climate change, but more likely a response to global atmospheric circulation.;

Abstract Liver fibrosis could be the last hope for treating liver cancer and remodeling of the hepatic microenvironment has emerged as a strategy to promote the ablation of liver fibrosis. In recent years, especially with the rapid development of nanomedicine, hepatic microenvironment therapy has been widely researched in studies concerning liver cancer and fibrosis. In this comprehensive review, we summarized recent advances in nano therapy-based remodeling of the hepatic microenvironment. Firstly, we discussed novel strategies for regulatory immune suppression caused by capillarization of liver sinusoidal endothelial cells (LSECs) and macrophage polarization. Furthermore, metabolic reprogramming and extracellular matrix (ECM) deposition are caused by the activation of hepatic stellate cells (HSCs). In addition, recent advances in ROS, hypoxia, and impaired vascular remodeling in the hepatic fibrotic microenvironment due to ECM deposition have also been summarized. Finally, emerging nanotherapeutic approaches based on correlated signals were discussed in this review. We have proposed novel strategies such as engineered nanotherapeutics targeting antigen-presenting cells (APCs) or direct targeting T cells in liver fibrotic immunotherapy to be used in preventing liver fibrosis. In summary, this comprehensive review illustrated the opportunities in drug targeting and nanomedicine, and the current challenges to be addressed. Graphical Abstract

Seed cotton yield and fiber quality are two primary factors that influence the international competitiveness of cotton. To enhance the water-nitrogen utilization efficiency and promote the sustainable cotton production, field experiments were performed in 2020 and 2021 to explore the effects of irrigation depth and nitrogen (N) fertilization rate on N uptake and distribution, seed cotton yield, fiber quality traits and water-nitrogen utilization efficiency in the Korla region of southern Xinjiang, China. Three irrigation depths (W1: 60% ETc, W2: 80% ETc, W3: 100% ETc; ETc was crop water consumption) and four N rates (N0: 0 kg ha−1, N200: 200 kg ha−1, N300: 300 kg ha−1, N400: 400 kg ha−1) were applied. The results showed irrigation depth and N rate significantly influenced N uptake and distribution in plant organs, seed cotton yield, crop water productivity (WP), partial factor productivity of nitrogen (PFPN) and some fiber quality traits. Increasing irrigation depth improved plant height, leaf area index, aboveground dry matter and seed cotton yield, while increasing N rate increased and then declined these indicators. At the squaring and flowering stages, the N accumulation in all parts of cotton increased as irrigation depth and N rate increased, whereas it increased and then declined with increasing N rate at the boll-setting and harvesting stages. At the squaring and flowering stages, N was mainly accumulated in the leaves. As the growth period progressed, N was transported to bolls and the proportion of N content in leaves decreased. The proportion of N accumulation in cotton bolls was largest at the boll-setting and harvesting stages, and the N accumulation in plant organs followed the order of boll > leaf > stem > root. As irrigation depth increased, PFPN increased but WP decreased. As N rate increased, PFPN decreased but WP increased and then declined. The increases in N rate improved fiber quality. The maximum seed cotton yield (7578 kg ha−1 in 2020 and 7173 kg ha−1 in 2021) and greater WP, PFPN and fiber quality occurred in W3N300, which was recommended as a sustainable cotton production strategy in the Korla region of southern Xinjiang and elsewhere with similar environments to improve water-nitrogen utilization efficiency, seed cotton yield and alleviate soil nitrate pollution risk.

In this study, zebrafish (Danio rerio) were exposed to polystyrene nanoplastics (PS-NPs, 80 nm) at 0, 15, or 150 μg/L for 21 days and supplied with a low or high vitamin D (VD) diet (280 or 2800 IU/kg, respectively, indicated by – or +) to determine whether and how VD can regulate lipid metabolism disorder induced by PS-NPs. Six groups were created according to the PS-NP concentration and VD diet status: 0−, 0+, 15−, 15+,150−, and 150 +. Transmission electron microscopy showed that PS-NPs accumulated in the livers of zebrafish, which led to large numbers of vacuoles and lipid droplets in liver cell matrices; this accumulation was most prominent in the 150− group, wherein the number of lipid droplets increased significantly by 136.36%. However, the number of lipid droplets decreased significantly by 76.92% in the 150+ group compared with the 150− group. An examination of additional biochemical indicators showed that the high VD diet partially reversed the increases in the triglyceride and total cholesterol contents induced by PS-NPs (e.g., triglycerides decreased by 58.52% in the 150+ group, and total cholesterol decreased by 44.64% in the 15+ group), and regulated lipid metabolism disorder mainly by inhibiting lipid biosynthesis. Untargeted lipidomics analysis showed that exposure to PS-NPs was associated mainly with changes in the lipid molecular content related to cell membrane function and lipid biosynthesis and that the high VD diet reduced the content of lipid molecules related to lipid biosynthesis, effectively alleviating cell membrane damage and lipid accumulation. These findings highlight the potential of VD to alleviate lipid metabolism disorder caused by PS-NP exposure, thereby providing new insights into how the toxic effects of NPs on aquatic organisms could be reduced.

Liver fibrosis remains a serious problem affecting the health of millions of people worldwide. Hepatic stellate cells (HSCs) are the main effector cells in liver fibrosis and their activation could lead to extracellular matrix deposition, which may aggravate the development of liver fibrosis and inflammation. Previous studies have reported the potential of Phillygenin (PHI) as a hepatoprotective agent to inhibit HSCs activation and fibrosis development. However, the poor water solubility of PHI hinders its clinical application as a potential anti-liver fibrosis therapy. Milk-derived exosomes (mEXO) serve as scalable nanocarriers for delivering chemotherapeutic agents due to their excellent biocompatibility. Here, we developed a PHI-Hyaluronic acid (HA) composite mEXO (PHI-HA-mEXO) drug delivery system, in which DSPE-PEG2000-HA was conjugated to the surface of mEXO to prepare HA-mEXO, and PHI was encapsulated into HA-mEXO to form PHI-HA-mEXO. As a specific receptor for HA, CD44 is frequently over-expressed during liver fibrosis and highly expressed on the surface of activated HSCs (aHSCs). PHI-HA-mEXO can bind to CD44 and enter aHSCs through endocytosis and release PHI. PHI-HA-mEXO drug delivery system can significantly induce aHSCs death without affecting quiescent HSCs (qHSCs) and hepatocytes. Furthermore, we carried out in vitro and in vivo experiments and found that PHI-HA-mEXO could alleviate liver fibrosis through aHSCs-targeted mechanism. In conclusion, the favorable biosafety and superior anti-hepatic fibrosis effects suggest a promising potential of PHI-HA-mEXO in the treatment of hepatic fibrosis. However, detailed pharmokinetics and dose-responsive experiments of PHI-HA-mEXO and the mechanism of mEXO loading drugs are still required before PHI-HA-mEXO can be applied clinically.

Abstract Bacterial vaginosis (BV) is a disease caused by vaginal microbiota dysbiosis. Here, we propose the use of synthetic bacterial consortia transplantation (SBCT) for the treatment of Gardnerella vaginalis-induced BV mice. The results showed that SBCT significantly reduced vaginal tissue damage and restored the vaginal microbiota, decreased the secretion of pro-inflammatory cytokines (IL-1β and IL-8), and suppressed NF-κB activation. IL-17, iNOS, and COX-2 expression in vaginal tissue were also down-regulated. However, IL-10 and Foxp3 showed up-regulated expression in mice. Compared with vaginal microbiota transplantation (VMT), results indicated that VMT was more effective than SBCT in suppressing G. vaginalis-induced inflammation. The obtained results suggest that synthetic bacterial consortia might be used as a potential biotherapeutic agent for the treatment of G. vaginalis-induced bacterial vaginosis. Video Abstract

In recent years, Graph Neural Networks (GNNs) based on deep learning techniques have achieved promising results in EEG-based depression detection tasks but still have some limitations. Firstly, most existing GNN-based methods use pre-computed graph adjacency matrices, which ignore the differences in brain networks between individuals. Additionally, methods based on graph-structured data do not consider the temporal dependency information of brain networks. To address these issues, we propose a deep learning algorithm that explores adaptive graph topologies and temporal graph networks for EEG-based depression detection. Specifically, we designed an Adaptive Graph Topology Generation (AGTG) module that can adaptively model the real-time connectivity of the brain networks, revealing differences between individuals. In addition, we designed a Graph Convolutional Gated Recurrent Unit (GCGRU) module to capture the temporal dynamical changes of brain networks. To further explore the differential features between depressed and healthy individuals, we adopt Graph Topology-based Max-Pooling (GTMP) module to extract graph representation vectors accurately. We conduct a comparative analysis with several advanced algorithms on both public and our own datasets. The results reveal that our final model achieves the highest Area Under the Receiver Operating Characteristic Curve (AUROC) on both datasets, with values of 83% and 99%, respectively. Furthermore, we perform extensive validation experiments demonstrating our proposed method’s effectiveness and advantages. Finally, we present a comprehensive discussion on the differences in brain networks between healthy and depressed individuals based on the outputs of our final model’s AGTG and GTMP modules.

Many software suites and spectral libraries have been developed for DIA proteomics data analysis. Here, the authors create benchmark data sets to evaluate four commonly used software tools combined with seven spectral libraries in both global proteomics and phosphoproteomics analysis.

Abstract Background Occupational exposure to blood and body fluids poses a threat to medical providers and to nurses especially. This harm is not only physical, but psychology as well and can ultimately impact patient safety. This study aims to understand the prevalence of occupational exposure to blood and body fluids among Chinese registered nurses and explores the factors that influence this exposure. Methods A cross-sectional online survey was conducted for 31 province-level divisions in China, using a self-created questionnaire entitled Status Survey on Occupational Exposure in Nurses. Descriptive statistics were used to describe both the demographic characteristics of the respondents and the characteristics of occupational exposure. Categorical variables were presented as frequencies and percentage, and the relationship between possible influential factors and the occurrence of occupational exposure was determined using binary logistic regression. Results Out of a total of 20,791 nurses analyzed, over half (52.1%) of them had experienced occupational exposure to blood or body fluids, but over 1/3 (34.6%) of them did not ever report their exposures to a supervisor/official. The top three causes of under-reporting were: the source patient failed to test positive for infectious pathogens (43.6%), perception of a burdensome reporting process (24.6%), and indifferent attitude towards being infected (16.9%). Nurses who worked over 8 hours per day had higher risks of exposure (OR 1.199, 95% CI 1.130 to 1.272, P

The gut microbiota consistently shows strong correlations with lipid metabolism in humans and animals, and whether the gut microbiota contributes to muscle fatty acid (FA) deposition and meat traits in farm animals has not been fully resolved. In this study, we aimed to unveil the microbial mechanisms underlying muscle FA deposition in pigs. First, we systematically revealed the correlation between the gut microbiome and muscle FA levels in 43 obese Ningxiang pigs and 50 lean Duroc Landrace Yorkshire (DLY) pigs. Mutual fecal microbial transplantation showed that the obese Ningxiang pig-derived microbiota increased the muscle FA content and improved meat quality by reshaping the gut microbial composition in lean DLY pigs. Lactobacillus reuteri has been identified as a potential microbial biomarker in obese Ningxiang pig-derived microbiota-challenged DLY pigs. A gavage experiment using lean DLY pigs confirmed that L. reuteri XL0930 isolated from obese Ningxiang pigs was the causal species that increased the muscle FA content. Mechanistically, SLC22A5, a carnitine transporter, was downregulated in L. reuteri XL0930-fed DLY pigs, resulting in reduced muscle carnitine levels. Muscle and intestinal L-carnitine levels, which correlated with the muscle FA content, impeded fat synthesis and FA accumulation in in vitro and in vivo models. In conclusion, we uncovered an unexpected and important role of the obese Ningxiang pig-derived microbiota in regulating muscle FA metabolism via the SLC22A5-mediated carnitine system.

IntroductionElectroencephalographic (EEG) abnormalities are seen in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) with characteristic features of cognitive impairment. The most common findings of EEG features in AD and MCI patients are increased relative power of slow oscillations (delta and theta rhythms) and decreased relative power of fast oscillations (alpha, beta and gamma rhythms). However, impairments in cognitive processes in AD and MCI are not sufficiently reflected by brain oscillatory activity in a particular frequency band. MCI patients are at high risk of progressing to AD. Cross-frequency coupling (CFC), which refers to coupling between different frequency bands, is a crucial tool for comprehending changes in brain oscillations and cognitive performance. CFC features exhibit some specificity in patients with AD and MCI, but a comparison between CFC features in individuals with these disorders is still lacking. The aim of this study was to explore changes in CFC properties in MCI and AD and to explore the relationship between CFC properties and multiple types of cognitive functional performance.MethodsWe recorded resting-state EEG (rsEEG) signals in 46 MCI patients, 43 AD patients, and 43 cognitively healthy controls (HCs) and analyzed the changes in CFC as well as the relationship between CFC and scores on clinical tests of cognitive function.Results and discussionMultiple couplings between low-frequency oscillations and high-frequency oscillations were found to be significantly enhanced in AD patients compared to those of HCs and MCI, while delta-gamma as well as theta-gamma couplings in the right temporal and parietal lobes were significantly enhanced in MCI patients compared to HCs. Moreover, theta-gamma coupling in the right temporal lobe tended to be stronger in MCI patients than in HCs, and it was stronger in AD than in MCI. Multiple CFC properties were found to correlate significantly with various cognitive domains, especially the memory function domain. Overall, these findings suggest that AD and MCI patients must use more neural resources to maintain a resting brain state and that alterations in theta-gamma coupling in the temporal lobe become progressively obvious during disease progression and are likely to be a valuable indicator of MCI and AD pathology.

Objective Risk stratification is challenging in patients with acute ST segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI). We investigated the prognostic value of a novel score system combining leucocyte and platelet counts (COL-P) scores for in-hospital and long-term adverse outcomes.Design This was a retrospective cohort study of patients with STEMI.Setting First Affiliated Hospital of Xinjiang Medical University.Participants A total of 854 STEMI patients with primary PCI were included in this study from November 2009 and December 2015.Primary and secondary outcome measures Major adverse cardiovascular events (MACEs).Methodology The patients were divided into three groups according to the COL-P scores (0, 1 and 2). Cox regression analysis was used to investigate the relation between adverse outcomes and the COL-P score in patients with STEMI.Results A total of 44 patients died in hospital, and 99 within 3-year follow-up after discharge. The in-hospital and 3-year mortality and MACEs were higher in patients with higher COL-P score. Multivariable Cox regression indicated COL-P score was independently associated with long-term mortality (COL-P 1 vs COL-P 0: HR 2.07, 95% CI 1.016 to 5.567, p=0.005; COL-P 2 vs COL-P 0: HR 5.02, 95% CI 1.990 to 9.041, p

BackgroundAlzheimer’s disease (AD) is one of the world’s well-known neurodegenerative diseases, which is related to the balance mechanism of production and clearance of two proteins (amyloid-β and tau) regulated by the glymphatic system. Latest studies have found that AD patients exhibit impairments to their glymphatic system. However, the alterations in the AD disease continuum, especially in the early stages, remain unclear. Moreover, the relationship between the glymphatic system and cognitive dysfunction is still worth exploring.MethodsA novel diffusion tensor image analysis method was applied to evaluate the activity of the glymphatic system by an index for diffusivity along the perivascular space (ALPS-index). Based on this method, the activity of the glymphatic system was noninvasively evaluated in 300 subjects, including 111 normal controls (NC), 120 subjects with mild cognitive impairment (MCI), and 69 subjects with AD. Partial correlation analysis was applied to explore the association between glymphatic system and cognitive impairment based on three domain-general scales and several domain-specific cognitive scales. Receiver operating characteristic curve analysis was used to evaluate the classification performance of ALPS-index along the AD continuum.ResultsALPS-index was significantly different among NC, MCI and AD groups, and ALPS-index decreased with cognitive decline. In addition, ALPS-index was significantly correlated with the scores of the clinical scales (p

Probiotic intervention is a well-established approach for replacing antibiotics in the management of weaning piglet diarrhea, which involves a large number of complex systems interacting with the gut microbiota, including the endocannabinoid system; nevertheless, the specific role of the endocannabinoid system mediated by probiotics in the piglet intestine has rarely been studied. In this study, we used antibiotics (ampicillin) to perturb the intestinal microbiota of piglets. This resulted in that the gene expression of the intestinal endocannabinoid system was reprogrammed and the abundance of probiotic Lactobacillus johnsonii in the colon was lowered. Moreover, the abundance of Lactobacillus johnsonii was positively correlated with colonic endocannabinoid system components (chiefly diacylglycerol lipase beta) via correlation analysis. Subsequently, we administered another batch of piglets with Lactobacillus johnsonii. Interestingly, dietary Lactobacillus johnsonii effectively alleviated the diarrhea ratio in weaning piglets, accompanied by improvements in intestinal development and motility. Notably, Lactobacillus johnsonii administration enhanced the intestinal barrier function of piglets as evidenced by a higher expression of tight junction protein ZO-1, which might be associated with the increased level in colonic diacylglycerol lipase beta. Taken together, the dietary Lactobacillus johnsonii-mediated reprogramming of the endocannabinoid system might function as a promising target for improving the intestinal health of piglets.

Abstract Energy shortage and environmental concern urgently require establishing the feasible bio-refinery process from various feedstocks. The methylotrophic yeast Ogataea polymorpha is thermo-tolerant and can utilize various carbon sources, such as glucose, xylose and methanol, which makes it a promising host for bio-manufacturing. Here, we explored the capacity of O. polymorpha for overproduction of free fatty acids (FFAs) from multiple substrates. The engineered yeast produced 674 mg/L FFA from 20 g/L glucose in shake flask and could sequentially utilize the mixture of glucose and xylose. However, the FFA producing strain failed to survive in sole methanol and supplementing co-substrate xylose promoted methanol metabolism. A synergistic utilization of xylose and methanol was observed in the FFA producing strain. Finally, a mixture of glucose, xylose and methanol was evaluated for FFA production (1.2 g/L). This study showed that O. polymorpha is an ideal host for chemical production from various carbon sources. Graphical Abstract

BackgroundComputer-aided detection, used in the screening and diagnosing of cognitive impairment, provides an objective, valid, and convenient assessment. Particularly, digital sensor technology is a promising detection method. ObjectiveThis study aimed to develop and validate a novel Trail Making Test (TMT) using a combination of paper and electronic devices. MethodsThis study included community-dwelling older adult individuals (n=297), who were classified into (1) cognitively healthy controls (HC; n=100 participants), (2) participants diagnosed with mild cognitive impairment (MCI; n=98 participants), and (3) participants with Alzheimer disease (AD; n=99 participants). An electromagnetic tablet was used to record each participant’s hand-drawn stroke. A sheet of A4 paper was placed on top of the tablet to maintain the traditional interaction style for participants who were not familiar or comfortable with electronic devices (such as touchscreens). In this way, all participants were instructed to perform the TMT-square and circle. Furthermore, we developed an efficient and interpretable cognitive impairment–screening model to automatically analyze cognitive impairment levels that were dependent on demographic characteristics and time-, pressure-, jerk-, and template-related features. Among these features, novel template-based features were based on a vector quantization algorithm. First, the model identified a candidate trajectory as the standard answer (template) from the HC group. The distance between the recorded trajectories and reference was computed as an important evaluation index. To verify the effectiveness of our method, we compared the performance of a well-trained machine learning model using the extracted evaluation index with conventional demographic characteristics and time-related features. The well-trained model was validated using follow-up data (HC group: n=38; MCI group: n=32; and AD group: n=22). ResultsWe compared 5 candidate machine learning methods and selected random forest as the ideal model with the best performance (accuracy: 0.726 for HC vs MCI, 0.929 for HC vs AD, and 0.815 for AD vs MCI). Meanwhile, the well-trained classifier achieved better performance than the conventional assessment method, with high stability and accuracy of the follow-up data. ConclusionsThe study demonstrated that a model combining both paper and electronic TMTs increases the accuracy of evaluating participants’ cognitive impairment compared to conventional paper-based feature assessment.

Legacy per- and polyfluoroalkyl substances (PFASs) have elicited much concern because of their ubiquitous distribution in the environment and the potential hazards they pose to wildlife and human health. Although an increasing number of effective PFAS alternatives are available in the market, these alternatives bring new challenges. This paper comprehensively reviews how PFASs bind to transport proteins (e.g., serum albumin, liver fatty acid transport proteins and organic acid transporters), nuclear receptors (e.g., peroxisome proliferator activated receptors, thyroid hormone receptors and reproductive hormone receptors) and membranes (e.g., cell membrane and mitochondrial membrane). Briefly, the hydrophobic fluorinated carbon chains of PFASs occupy the binding cavities of the target proteins, and the acid groups of PFASs form hydrogen bonds with amino acid residues. Various structural features of PFAS alternatives such as chlorine atom substitution, oxygen atom insertion and a branched structure, introduce variations in their chain length and hydrophobicity, which potentially change the affinity of PFAS alternatives for endogenous proteins. The toxic effects and mechanisms of action of legacy PFASs can be demonstrated and compared with their alternatives using binding models. In future studies, in vitro experiments and in silico quantitative structure–activity relationship modeling should be better integrated to allow more reliable toxicity predictions for both legacy and alternative PFASs.

BackgroundThe involvement of retina and its vasculature has been recently described in Alzheimer’s disease (AD). Optical coherence tomography angiography (OCTA) is noninvasively used to assess the retinal blood flow.ObjectiveThis study was to compare vessel density (VD) and blood perfusion density (PD) of the macular in AD patients, mild cognitive impairment (MCI) patients and healthy controls by OCTA, which may provide new ideas for diagnosis of AD or MCI.MethodsAD patients, MCI patients and healthy controls underwent a comprehensive ophthalmic and neurological evaluations, including cognitive function assessments as well as visual acuity, intraocular pressure (IOP), slit lamp examinations, and OCTA. General demographic data, cognitive function, retinal VD and PD were compared among three groups. The correlations among retinal VD, PD and cognitive function, amyloid-beta (Aβ) protein and phosphorylated Tau (p-Tau) protein were further evaluated. The correlations between retinal superficial capillary plexus and cognitive function, Aβ protein and p-Tau protein were also explored.ResultsA total of 139 participants were recruited into this study, including 43 AD patients, 62 MCI patients, and 34 healthy controls. After adjusting for sex, age, history of smoking, history of alcohol intake, hypertension, hyperlipidemia, best corrected visual acuity, and IOP, VD and PD in the nasal and inferior regions of the inner ring, superior and inferior regions of outer ring in the AD group were significantly lower than in the control group (p

BackgroundNeck-shoulder pain is one of the most common discomfort symptoms among nursing staff, mostly caused by a heavy workload, restricted workstation, and prolonged poor posture.ObjectiveTo investigate the prevalence of neck-shoulder pain among nursing staff in tertiary general hospitals in Hunan Province, and to analyze workload-related risk factors.MethodsFrom October to December 2018, a multi-stage stratified randomized cluster sampling method was adopted to select a total of 1 200 nursing staff who met the inclusion andexclusion criteria in six tertiary general hospitals from five geographic subdivisions of Hunan Province were selected. A self-designed questionnaire was used to collect demographic characteristics, and past 1-month prevalence of neck-shoulder pain, a neck disability index (NDI) was used to assess the impact of neck pain on daily life, and functional disability was graded by the index of impaired neck function; a self-designed questionnaire was adopted to evaluate potential workload-related risk factors (working time, postural load, and force load) of neck-shoulder pain after a Delphi expert consultation. A total of 1 161 valid questionnaires were returned, and χ２test and logistic regression model were used to screen the potential risk factors for neck-shoulder pain.ResultsThe prevalence rate of neck-shoulder pain in the past 1 month was 87.5% (1 016/1 161) and varied by different characteristics of the nursing staff, ranging from 76.9% to 91.2%. The scores of the 10 items of the NDI ranged from 0 to 5, but most of them were 0, 1, and 2; of the 10 items, neck pain had the greatest impact on sleep (1.30±1.21) and the least impact on self-care behaviors (0.35±0.65). The index of impaired neck function showed that the majority (65.4%) of nurses had mild cervical spine dysfunction and 30.1% had moderate cervical spine dysfunction. The univariate analysis results revealed that 24 out of the 31 workload-related risk factors had significant differences, and further multiple analysis results showed that three variables entered the logistic regression model. Under the same conditions, nurses with ≥5 h of cumulative head-down tasks per shift had 3.03 times higher neck-shoulder pain risks compared with those with ＜1 h. Compared with “occasionally or never”, nurses who “sometimes” and “often” tilted their necks back and maintained this posture for a long time showed 2.36 and 2.94 times higher risks for neck-shoulder pain respectively. The nurses who reported “sometimes” and “often” having difficulty using their force at work due to unnatural posture had 2.78 times and 7.08 times higher neck-shoulder pain risks than those who “occasionally or never” respectively.ConclusionThe reported rate of neck-shoulder pain among nurses in tertiary general hospitals in Hunan Province is high, but most of them are mild dysfunction. Working hours and posture load may affect the risk of neck-shoulder pain.

Abstract α-Alkenes (terminal alkenes) are important fuel and platform chemicals that are mainly produced from petroleum. Microbial synthesis might provide a sustainable approach for α-alkenes. In this work, we engineered the methylotrophic yeast Pichia pastoris to produce long-chain (C15:1, C17:1 and C17:2) α-alkenes via a decarboxylation of fatty acids. Combinatorial engineering, including enzyme selection, expression optimization and peroxisomal compartmentalization, enabled the production of 1.6 mg/L α-alkenes from sole methanol. This study represents the first case of α-alkene biosynthesis from methanol and also provides a reference for the construction of methanol microbial cell factories of other high-value chemicals. Graphical Abstract

Background: Causal evidence of circulating lipids especially the remnant cholesterol with cardiovascular and cerebrovascular disease (CVD) is lacking. This research aimed to explore the causal roles of extensive lipid traits especially the remnant lipids in CVD. Methods: Two-sample Mendelian randomization (TSMR) analysis was performed based on large-scale meta-analysis datasets in European ancestry. The causal effect of 15 circulating lipid profiles including 6 conventional lipids and 9 remnant lipids on coronary heart disease (CHD) and ischemic stroke (IS), as well as the subtypes, was assessed. Results: Apolipoprotein B (Apo B), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were still important risk factors for CHD and myocardial infarction (MI) but not for IS. Apo B is the strongest which increased the CHD and MI risk by 44% and 41%, respectively. The odds ratios (ORs) of total TG on CHD and MI were 1.25 (95% confidence interval [CI], 1.13–1.38) and 1.24 (95% CI, 1.11–1.38), respectively. A one standard deviation difference increased TG in medium very-low-density lipoproteins (M.VLDL.TG), TG in small VLDL (S.VLDL.TG), TG in very small VLDL (XS.VLDL.TG), TG in intermediate-density lipoproteins (IDL.TG), TG in very large HDL (XL.HDL.TG), and TG in small HDL (S.HDL.TG) particles also robustly increased the risk of CHD and MI by 9–28% and 9–27%, respectively. TG in very/extremely large VLDL (XXL.VLDL.TG and XL.VLDL.TG) were insignificant or even negatively associated with CHD (in multivariable TSMR), and negatively associated with IS as well. Conclusion: The remnant lipids presented heterogeneity and two-sided effects for the risk of CHD and IS that may partially rely on the particle size. The findings suggested that the remnant lipids were required to be intervened according to specific components. This research confirms the importance of remnant lipids and provides causal evidence for potential targets for intervention.

Abstract Surgeons face great challenges in acquiring high-performance imaging because fluorescence probes with desired thermal stability remains rare. Here, hybrid lead sulfide/zinc sulfide quantum dots (PbS/ZnS QDs) nanostructures emitting in the long-wavelength end of the second near-infrared (NIR-IIb) window were synthesized and conjugated with Ribonuclease-A (RNase A). Such formed RNase A@PbS/ZnS QDs exhibited strong NIR IIb fluorescence and thermal stability, as supported by the photoluminescent emission assessment at different temperatures. This will allow the RNase A@PbS/ZnS QDs to provide stable fluorescence signals for long-time intraoperative imaging navigation, despite often happened, undesirable thermal accumulation in vivo. Compared to NIR-IIa fluorescence imaging, NIR-IIb vascular fluorescence imaging achieved larger penetration depth, higher signal/background ratios and nearly zero endogenous tissue autofluorescence. Moreover, these QDs illustrate the reliability during the real-time and long-time precise assessment of flap perfusion by clearly visualizing microvasculature map. These findings contribute to intraoperative imaging navigation with higher precision and lower risk. Graphical Abstract

Abstract Advancements in lymphography technology are essential for comprehensive investigation of the lymphatic system and its function. Here, a shortwave infrared (SWIR) luminescence imaging of lymphatic vessels is proposed in both normal and lymphatic dysfunction in rat models with PbS quantum dots (PbS Qdots). The lymphography with PbS Qdots can clearly and rapidly demonstrate the normal lymphatic morphology in both the tail and hind limb. More importantly, compared to ICG, SWIR luminescence imaging with PbS Qdots can easily identify the dominant lymphatic vessel and node with higher luminescence signal in rats. Moreover, lymphatic pump is identified as segment contracting sections with a size of ≈1 cm in rat by in vivo SWIR lymphograhy, which propose a direct feature for precise evaluation of lymphatic function. Notably, in vivo SWIR luminescence imaging with PbS Qdots also clearly deciphers the in vivo pattern of morphological and function recovery from lymphatic system in rat model. In summary, SWIR luminescence imaging with PbS Qdots can improve the lymphography and thus deepen the understanding of the morphology and structure of the lymphatic system as well as lymphatic function such as lymphatic pump, which will facilitate the diagnosis of lymphatic dysfunction in the future.

As a traditional Chinese medicine, rhubarb has been used in a variety of liver diseases and it is widely used in clinic to prevent and treat acute liver injury. Anthraquinone, as the main medicinal component of rhubarb, can reverse the further development of liver fibrosis caused by acute liver injury. In this study, metabonomics was used to explore the mechanism of different doses of rhubarb anthraquinone on acute liver injury in rats. Rhubarb anthraquinone was administered intragastric to rats at doses of 3.9, 7.8 and 15.6 mg/kg, respectively, for 7 days, and then 30% CCl4 was injected intraperitoneally at the dose of 1 ml/kg to replicate the acute liver injury model. The biochemical indicators content of ALT, AST, ALP, γ-GT, TG, TC, LDL, HDL in serum and GSH, Hyp, SOD, TNF-α, IL-6 and IL-8 in liver tissue extract were tested respectively, and liver tissue was histopathologically analysis. At the same time, UPLC-Q-TOF-MS combined with non-targeted metabolomics were used to study the metabolites and metabolic pathways of rhubarb anthraquinone in treating acute liver injury. Compared with normal rats, the contents of ALT, AST, ALP, TG, TC, LDL, γ-GT in serum and Hyp, MDA, IL-6, IL-8, TNF-α in the liver tissue extract were significantly increased in model rats (p < 0.05, p < 0.01), and the content of HDL in the serum was significantly decreased (p < 0.05); the activities of GSH and SOD in liver tissue extract were also significantly decreased (p < 0.05). After administration of rhubarb anthraquinone, compared with the model group, with the increase of dosage, some biochemical indexes showed opposite changes, and gradually approached to normal rats. 12 different metabolites were identified by metabonomics, and the biosynthesis and metabolism of phenylalanine, tyrosine and tryptophan, the metabolism of amino sugars, nucleotide sugars and pyrimidines metabolism, and the biosynthesis of steroid hormone were identified based on the biomarker analysis. Based on the biochemical analysis and metabonomics analysis of rats with acute liver injury treated with different doses of rhubarb anthraquinone, combined with histopathological observation, the results show that the protective effect of rhubarb anthraquinone on acute liver injury is related to the dosage; Meanwhile, the metabolic pathway analysis suggested that rhubarb anthraquinone alleviate acute liver injury by regulating inflammation, oxidative stress and fibrosis disorders. This study explained the therapeutic effect of rhubarb anthraquinone on acute liver injury from both material basis and action pathway, and provided safe and effective research ideas for clinical application of rhubarb.

A preliminary study has shown that 3, 8-Di-O-methylellagic acid 2-O-glucoside (DMAG), an ellagic tannin from Sanguisorba officinalis L., has the potential in relieving thrombocytopenia. However, there is a lack of information on the pharmacokinetics of DMAG in thrombocytopenia rats. Therefore, we aimed to establish a simple, rapid, and sensitive UHPLC-MS/MS method for quantifying DMAG and study its pharmacokinetic behavior in this study. DMAG and hispidulin (internal standard, IS) were separated on an Acquity Shim-pack GIST column using 0.1% formic acid in water and acetonitrile as the mobile phase with a total run time of 5 min and gradient elution at a flow rate of 0.3 mL/min. The recovery and matrix effects of DMAG were within 94.85%–100.40% and 94.55%–102.46%, respectively. The intraday RSD and interday RSD were between 3.31% and 13.19%, accuracy RE was ≤6.69%, and stability RSD changes were 3.38%–8.78%. As for intragastric administration, with shortened Tmax (3.00 vs. 2.16 h), Cmax (25.67 vs. 35.38 ng/mL) was added for a 2 mg/kg dose after the establishment of the thrombocytopenia rat model. Relative to normal rats treated with 4 mg/kg, in thrombocytopenia rats treated with the same dose, Cmax (49.13 vs. 67.78 ng/mL), AUC(0–t) (234.60 vs. 318.17 ng·h/mL), and AUC(0–∞) (322.74 vs. 498.57 ng h/mL) increased, MRT (18.15 vs. 26.32 h) prolonged, Tmax (3.00 vs. 2.33 h) shortened, and CL/F (12746.50 vs. 8093.50 mL/h/kg) reduced. As for intravenous administration, Cmax (1679.54 ng/mL), AUC(0–t) (589.02 g·h/mL), and AUC(0–∞) (605.58 g·h/mL) were significantly increased in thrombocytopenia rats than that in normal rats (743.76 ng/mL for Cmax, 242.46 g·h/mL for AUC(0–t), and 245.19 g·h/mL for AUC(0–∞)). Vz/F and CL/F were remarkably decreased from 343196.86 to 194659.43 mL/kg for Vz/F and 8236.18 to 3326.01 mL/h/kg for CL/F with the model establishment, respectively. Overall, we successfully developed a reliable UHPLC-MS/MS method for determining DMAG levels in rat plasma. The pharmacokinetic difference could be attributed to the pathological state of the thrombocytopenia rats, which may affect the absorption, distribution, metabolism, and excretion of DMAG. These findings lay the foundation for further evaluating the clinical efficiency and safety of DMAG in the treatment of thrombocytopenia.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Papillary thyroid microcarcinoma (PTMC) is defined as PTC with a diameter less than 1 centimeter. Most lymph nodes of PTC patients have metastasized to the central neck, and a few lymph nodes have metastasized to the lateral neck. Skip lymph node metastasis, that is, lateral cervical lymph node metastasis without central lymph node metastasis, is even less common. Additionally, distant metastasis of PTMC is also rare, mainly occurring in the lung and bone. Here, we reported a case of PTMC patient with skip lymph node metastasis and multiple distant metastasis. The patient presented with a huge shoulder mass and the primary tumor was found to originate from the thyroid. However, the patient only suffered with PTMC via postoperative pathological results, and interestingly, the patient only had skip lymph node metastasis. Thus, we should focus on PTMC patients with lateral cervical lymph nodes metastasis, especially those with skip metastasis. In addition, this case provides a new perspective for us to understand of skip lymph metastasis and distant metastasis of PTMC.

Objective Owing to the lack of a breeding index for efficient and quick fertility evaluations of Holstein bulls when using traditional or genome-wide detection methods, this study aimed to determine whether in vitro fertilization (IVF) could be used as an indicator of conception rate of artificial insemination (AI). Methods Conventional and sexed frozen semen from nine bulls were used for IVF and AI. Results The IVF and AI conception rates of each bull were confirmed to be positively correlated between the conventional frozen and sexed frozen semen. The correlation coefficient R values of nine bulls between IVF and AI methods were 0.73 and 0.97 for the conventional frozen and sexed frozen semen, respectively. The average conception rate of three bulls undergoing AI was 69.5% and 64.2%, 61.8% and 58.8%, and 48.2% and 46.2% in first-, second-, and third-born cows when conventional frozen and sexed frozen semen were used, respectively, which showed a positive correlation with the fertilization rate in the same parity. We propose an evaluation standard to assess the fertilization ability of bulls based on their IVF test results, which is categorized into three grades: grade one, normal fertility bull with an AI conception rate of 40%±5% and IVF rate of 45% to 60%; grade two, higher fertility bull with an AI conception rate of 50%±5% and IVF rate of 61% to 80%; and grade three, highest fertility bull with an AI conception rate of 60%±5% and IVF rate of >80%. Conclusion These findings reveal that IVF results can be used as a breeding index for bulls to evaluate their AI conception ability, which may shorten the time required to select bulls for breeding.

Abstract Background Brain atrophy is an important feature in dementia and is meaningful to explore a brain atrophy model to predict dementia. Using machine learning algorithm to establish a dementia model and cognitive function model based on brain atrophy characteristics is unstoppable. Method We acquired 157 dementia and 156 normal old people.s clinical information and MRI data, which contains 44 brain atrophy features, including visual scale assessment of brain atrophy and multiple linear measurement indexes and brain atrophy index. Five machine learning models were used to establish prediction models for dementia, general cognition, and subcognitive domains. Results The extreme Gradient Boosting (XGBoost) model had the best effect in predicting dementia, with a sensitivity of 0.645, a specificity of 0.839, and the area under curve (AUC) of 0.784. In this model, the important brain atrophy features for predicting dementia were temporal horn ratio, cella media index, suprasellar cistern ratio, and the thickness of the corpus callosum genu. Conclusion For nonstroke elderly people, the machine learning model based on clinical head MRI brain atrophy features had good predictive value for dementia, general cognitive impairment, immediate memory impairment, word fluency disorder, executive dysfunction, and visualspatial disorder.

Artemisia argyi leaf is a well-known species in traditional Chinese medicine, and its essential oil (AAEO) has been identified to exert various physiological activities. The aim of this study was to investigate the effects of AAEO on lipid metabolism and the potential microbial role in high-fat diet (HFD)-fed mice. A total of 50 male mice were assigned to five groups for feeding with a control diet (Con), a high-fat diet (HFD), and the HFD plus the low (LEO), medium (MEO), and high (HEO) doses of AAEO. The results demonstrated that dietary HFD markedly increased the body weight gain compared with the control mice (p < 0.05), while mice in the HEO group showed a lower body weight compared to the HFD group (p < 0.05). The weight of fatty tissues and serum lipid indexes (TBA, HDL, and LDL levels) were increased in response to dietary HFD, while there was no significant difference in AAEO-treated mice (p < 0.05). The jejunal villus height was dramatically decreased in HFD-fed mice compared with the control mice, while HEO resulted in a dramatically higher villus height than that in the HFD group (p < 0.05). Microbial α-diversity was not changed in this study, but β-diversity indicated that microbial compositions differed in control, HFD, and EO subjects. At the genus level, the relative abundance of Bacteroides was greater (p < 0.05) in the feces of the Con group when compared to the HFD and EO groups. On the contrary, the abundance of Muribaculum was lower in the Con group compared to the HFD and EO groups (p < 0.05). Although the Muribaculum in the EO group was lower than that in the HFD group, there was no statistically notable difference between the HFD and EO groups (p > 0.05). Simultaneously, the relative abundance of Alistipes (p < 0.05) and Rikenella (p < 0.05) was also dramatically higher in the Con group than in the HFD and EO groups. The abundance of norank_f__norank_o__Clostridia_UCG-014 was lower in the HFD or EO group than in the Con group (p < 0.05). In conclusion, the results suggested that HEO could affect body weight and lipid metabolism without gut microbes in ICR mice, and it was beneficial for the structure of the jejunal epithelial tissue.