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Spermatogenesis is a complex process intricately regulated by the hypothalamic-pituitary-testis (HPT) axis. However, research on the regulatory factors governing the HPT axis remains limited. This study addresses this gap by conducting a comprehensive analysis of transcriptomes from the pituitary and testis tissues across various developmental stages, encompassing embryonic day (E120), neonatal period (P0), pre-puberty (P90), and post-puberty day (P270). Utilizing edgeR and WGCNA, we identified stage-specific genes in both the pituitary and testis throughout the four developmental stages. Notably, 380, 242, 34, and 479 stage-specific genes were identified in the pituitary, while 886, 297, 201, and 3,678 genes were identified in the testis. Subsequent analyses unveiled associations between these stage-specific genes and crucial pathways such as the cAMP signaling pathway, GnRH secretion, and male gamete generation. Furthermore, leveraging single-cell data from the pituitary and testis, we identified some signaling pathways involving BMP, HGF, IGF, and TGF-β, highlighting mutual regulation between the pituitary and testis at different developmental stages. This study sheds light on the pivotal role of the pituitary-testis axis in the reproductive process of sheep across four distinct developmental stages. Additionally, it delves into the intricate regulatory networks governing reproduction, offering novel insights into the dynamics of the pituitary-testis axis within the reproductive system.

BackgroundKnee osteoarthritis (KOA) is reputedly the most common musculoskeletal disease of the lower limbs and the main cause of pain and disability among older individuals. Pain is the most significant and widespread symptom of KOA. The descending pain inhibitory system has a cardinal role in normal pain consciousness, and its malfunction may be one of the pathophysiological mechanisms in KOA. Crucially, the rostral ventromedial medulla (RVM) and periaqueductal gray (PAG), as important components of the descending pain inhibitory system, directly modulate the activity of the spinal neurons involved in pain transmission. Tuina, a manual therapy, is effective and safe for reducing clinical symptoms of KOA; however, the mechanism that influences pain through the descending pain inhibitory system in KOA is unclear. ObjectiveThis study aims to investigate the modulatory implications of Tuina on the RVM and PAG, which have critical roles in the descending pain inhibitory system in patients with KOA. MethodsThis randomized controlled parallel trial will be conducted at the Tuina Clinic of the Third Affiliated Hospital of Henan University of Chinese Medicine (Zhengzhou, China). Patients with KOA will be randomly assigned (1:1) to 6 weeks of health education or Tuina. All patients in both groups will accept a resting-state functional magnetic resonance scan at the beginning and end of the experiment, and the resting-state functional connectivity and the voxel-based morphometry analysis will be performed to detect the RVM and PAG function and structure changes. The clinical outcome assessments will be (1) the pressure pain thresholds, (2) the Numerical Rating Scale, (3) the Hamilton Depression Scale (HAMD), and (4) the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Considering that this trial is a study of resting-state functional magnetic resonance imaging technology, resting-state functional connectivity and voxel-based morphometry are the primary outcomes, and clinical outcome assessments are secondary outcomes. Adverse events will be documented and assessed throughout. All main analyses will be carried out on the basis of the intention-to-treat principle. The outcome evaluators and data statisticians will be masked to the treatment group assignment to reduce the risk of bias. ResultsThis trial was approved by the ethics committee of the Third Affiliated Hospital of Henan University of Chinese Medicine. Enrollment began in December 2023, and the results of this trial are expected to be submitted for publication in May 2025. ConclusionsThis trial will identify a possible relationship between function and structure changes of RVM and PAG and the improvement of clinical variables, elucidating the effect of Tuina on the descending pain inhibitory system of patients with KOA. This trial will provide much-needed knowledge for Tuina for patients with KOA. Trial RegistrationChinese Clinical Trial Registry ChiCTR2300070289; https://www.chictr.org.cn/showproj.html?proj=182570 International Registered Report Identifier (IRRID)PRR1-10.2196/52820

The trees in a given stand compete with each other for light, water and nutrients, producing spatial effects. To understand spatial effects, it is critical to characterise the spatial distributions and patterns of the aboveground biomass (AGB) of individual trees and the biomass of their components (stem, bark, branches and foliage). This study investigated the spatial effects by examining the AGB of individual trees and the biomass of their components in the context of typical sub-tropical tree species in Yunnan, China, including a Pinus kesiya var. langbianensis natural forest (PN), a Pinus kesiya var. langbianensis plantation (PP), and a Eucalyptus spp. plantation (EP), using datasets for three clear-cutting plots. Ripley’s L function was employed to identify the spatial distributions and patterns of the AGB of individual trees and the biomass of their components. Then, Global and Local Moran’s I indices were utilised to analyse spatial autocorrelation, with Intra-group variance being calculated to quantify spatial heterogeneity. This led to following findings. Firstly, with increasing distance, the spatial heterogeneity of the three stands increased before stabilising at a distance of 10 m. Secondly, excluding bark, all components of the tree biomass in the PN stand exhibited significant dispersion. In contrast, all the components in the PP stand showed significant dispersion. The spatial distributions and patterns of trees and their biomass in the EP stand indicated the coexistence of clustering and dispersion. Moreover, the significant spatial autocorrelations of tree AGB and components biomass could be noticed but depending on the stands, components and distances. These findings provide theoretical support for sustainable forest management based on biomass and carbon stocks.

Stroke has long been a major threat to human health worldwide. Hemorrhagic stroke, including intracerebral hemorrhage and subarachnoid hemorrhage, exhibits a high incidence rate and a high mortality and disability rate, imposing a substantial burden on both public health and the economy and society. In recent years, the triggering receptor expressed on myeloid cells (TREM) family has garnered extensive attention in various pathological conditions, including hemorrhagic stroke. This review comprehensively summarizes the structure and function of TREM1/2, as well as their roles and potential mechanisms in hemorrhagic stroke, with the aim of providing guidance for the development of targeted therapeutic strategies in the future.

There are currently no studies exploring omicron infection and male sexual function and semen quality. Our aim was to estimate changes in sexual function and semen quality in men recovering from infection since the COVID-19 Omicron pandemic started in China in late 2022. We collected 1540 questionnaires and assessed male function before infection and acute phase after infection by using International Index of Erectile Function-5, Premature Ejaculation Diagnostic Tool, and Arizona Sexual Experience Scale. We also collected the before and after semen analysis results of 247 male patients. During the acute phase after infection, the proportion of erectile dysfunction was significantly higher than before infection, but ejaculatory function was not significantly altered; In addition, semen analysis showed significant difference in semen concentration, semen activity and PR a+b sperm forward movement after infection compared to pre-infection.: COVID-19 Omicron can affect erectile function as well as sexual experience in male patients in the acute phase. Decreased sexual function due to COVID-19 Omicron may be related to body temperature and anxiety during infection.

In the process of long-term water flooding in the Gaoqian Southern Area with an average porosity of 30% and an average permeability of 1333.5×10−3 μm2, the fluid-solid interaction among oil, water, and rock has a great influence on the pore structure. It has resulted in changes in reservoir parameters with the extension of time. This paper used electron microscopy scanning, mercury injection, X-ray diffraction, physical properties, and oil-water relative permeability curves to study the variation of clay mineral content, pore throat structure, porosity, permeability, and relative permeability curves of high-permeability sandstone after high-pressure water flooding. The results showed that clay minerals such as montmorillonite and kaolinite were dissolved, hydrated, and migrated after long-term water flooding, which resulted in the decrease of clay mineral content in fine sandstone and medium sandstone, the increase of pore throat radius, and the decrease of displacement pressure, median pressure, and separation coefficient. The saturation of the isotonic point of the oil-water relative permeability curve was obviously shifted to the right, the hydrophilicity was significantly enhanced, and the porosity and permeability were effectively improved, but there was a blockage of the throat less than 2 μm in the fine sandstone. In addition, this paper established the equations of water injection, permeability, irreducible water saturation, residual oil saturation, and oil-water relative permeability curve coefficient and establishes the initial permeability model with the well data before water flooding. The logging interpretation results of development wells in the process of water flooding as verification data were used, and the relative error of permeability far lower than the general requirement of permeability error within an order of magnitude was less than 30%, which verified the rationality of the method.

Low back pain (LBP) is a leading cause of global disabilities. Numerous molecular, cellular, and anatomical factors are implicated in LBP. Current issues regarding neurologic alterations in LBP have focused on the reorganization of peripheral nerve and spinal cord, but neural mechanisms of exactly what LBP impacts on the brain required further researches. Based on existing clinical studies that chronic pain problems were accompanying alterations in brain structures and functions, researchers proposed logical conjectures that similar alterations occur in LBP patients as well. With recent extensive studies carried out using noninvasive neuroimaging technique, increasing number of abnormalities and alterations has been identified. Here, we reviewed brain alterations including white matters, grey matters, and neural circuits between brain areas, which are involved in chronic LBP. Moreover, brain structural and functional connectivity abnormalities are correlated to the happening and transition of LBP. The negative emotions related to back pain indicate possible alterations in emotional brain regions. Thus, the aim of this review is to summarize current findings on the alterations corresponding to LBP in the brain. It will not only further our understanding of etiology of LBP and understanding of negative emotions accompanying with back pain but also provide ideas and basis for new accesses to the diagnosis, treatment, and rehabilitation afterward based on integral medicine.

Background: The cachexia index (CXI) has been proposed as a novel biomarker of cancer cachexia. We aimed to investigate the association between CXI and survival outcomes after stereotactic radiotherapy (SRT) in patients with non-small cell lung cancer (NSCLC) and brain metastases. Methods: Data from 145 patients with NSCLC, who underwent SRT for brain metastases between April 2016 and August 2020, were retrospectively analyzed. Cachexia index was calculated as skeletal muscle index (SMI) × serum albumin level/neutrophil-to-lymphocyte ratio, whereas SMI was calculated from computed tomography images captured at the L1 level. Kaplan-Meier curves and Cox proportional hazards models were used to assess progression-free survival (PFS) and overall survival (OS). The prognostic values of CXI and other cachexia biomarkers were assessed using receiver operating characteristic (ROC) curve analysis. Results: Lower pretreatment CXI (

Objectives: To evaluate the efficacy and image processing time of the dynamic contrast-enhanced MRI (DCE-MRI) exchange model in liver fibrosis staging and compare it to the efficacy of magnetic resonance elastography (MRE). Methods: The subjects were 45 patients with nonalcoholic fatty liver disease (NAFLD) who underwent MRE and DCE-MRI in our hospital. Liver biopsy results were available for all patients. Spearman rank correlation coefficients were used to compare the correlations among MRE, DCE-MRI and liver fibrosis parameters. Quantitative DCE-MRI parameters, MRE-derived liver stiffness measurement (LSM), and the results of a combined DCE-MRI + MRE logistic regression model were compared in terms of the area under the receiver operating characteristic curve (AUC). We also compared the scanning and postprocessing times of the MRE and DCE-MRI techniques. Results: The correlation coefficients between the following parameters of interest and liver fibrosis were as follows: capillary permeability–surface area product (PS; DCE-MRI parameter), −0.761; portal blood flow (Fp; DCE-MRI parameter), −0.754; MRE-LSM, 0.835. Some DCE-MRI parameters (PS, Fp) had slightly greater AUC values than MRE-LSM for diagnosing the presence or absence of liver fibrosis, and the combined model had the highest AUC value for all stages except F4, but there was no significant difference in the diagnostic efficacy of the DCE-MRI, MRE, and combined models for any stage of fibrosis. The average scanning times for MRE and DCE-MRI were 17 s and 330 s, respectively, and the average postprocessing times were 45.5 s and 342.7 s, respectively. Conclusions: In the absence of MRE equipment, DCE-MRI represents an alternative technique. However, MRE is a quicker and simpler method for assessing fibrosis than DCE-MRI in the clinic.

BackgroundThere has existed controversy regarding the use of Ginkgo biloba (GKB) for blood metabolism among type 2 diabetes mellitus(T2DM) patients, and we tried to analyze the effects and safety of GKB on T2DM patients.MethodsWe conducted a literature search between January 2003 and December 2022 of seven online databases (PubMed, Scopus, Embase, Google Scholar, Web of Sciences, Cochrane Library, and China National Knowledge Infrastructure). A systematic literature review and meta-analysis were performed to compare the effects and safety of GKB among T2DM patients. Four groups of parameters were extracted and analyzed: hemorheology parameters, lipid profile, glycemic control markers, and adverse events.ResultsIn the end, 13 eligible articles with 11 indicators among 1573 patients were included. In the hemorheology parameters section, GKB showed significantly lower plasma viscosity (PV) (SMD=-0.91, 95%CI [-1.45, -0.36], P

Anthropogenic nutrient input stimulates surface eutrophication and algal blooms and thus exacerbates oxygen depletion and hypoxia in aquatic ecosystems. However, existing studies have paid little attention on the understanding of the feedback relationships among oxygen consumption, algal succession and greenhouse gas effect after river damming, particularly in Three Gorges Reservoir. This field work investigated the thermal stratification, water quality and phytoplankton in four tributaries (Pengxi Bay (PXB), Daning Bay (DNB), Shennong Bay (SNB), and Xiangxi Bay (XXB)) of the Three Gorges Reservoir (TGR) in spring (April 25-28, 2022), and explored the drivers of hypoxia and its feedback response to algal blooms and methane (CH4) emissions. The results showed that during the observation period, DO, thermal stratification, and algal blooms were more severe in PXB. The high Chemical Oxygen Demand (CODMn) (11.27 mg•L-1) and Dissolved Organic Carbon (DOC) content (7.56 mg•L-1) in PXB were the main causes of the progressive hypoxia. Furthermore, stronger density stratification in PXB inhibited the vertical supply of DO and accelerated bottom hypoxia. But the downslope density current replenished bottom DO in the upper reaches of the DNB, SNB, and XXB. The CH4 concentration was generally higher in hypoxia zone, especially in where cyanobacteria are the dominant species (eg., PX03 and PX04). Dam construction led to the succession of algal-dominant species, exerting a significant influence on the river carbon cycle. The expansion of cyanobacterial blooms and the consequence of metabolic substrates increase are gradually increasing oxygen deprivation, even hypoxia, and enhancing CH4 production in rivers. These findings suggest that the succession of algal-dominant species caused by river damming has a pronounced positive feedback effect on reservoir hypoxia processes and greenhouse effect.

Background: Previous studies have shown that the rs717620 polymorphism in ABCC2, the gene encoding multidrug resistance protein 2, influences the therapeutic response to anti-seizure medications (ASMs). However, this result is not consistent, and the mechanism by which rs717620 influences ASM responses is unclear. Aims: The present study evaluated the association between rs717620 genotype and ASM efficacy, and examined the potential mechanisms. Main: methods: We conducted a literature search of five electronic databases, Embase, Medline, Web of Science, China National Knowledge Infrastructure, and Wanfang, to identify relevant studies on response to ASM therapy among rs717620 genotypes. Expression quantitative trait loci analysis and drug–gene interaction analysis were also performed to assess the underlying mechanisms. Key findings: The pooled results for 18 studies revealed a significant association between rs717620 genotype and ASM resistance under the recessive model (TT vs. CT + CC: OR = 1.68, 95 % CI = 1.27–2.21, I2 = 3.1 %). A significant association was also found in the Asian population under the recessive model (TT vs. CT + CC: OR = 1.70, 95 % CI = 1.26–2.29, I2 = 29.3 %). Further analysis revealed that rs717620 regulates the expression of ABCC2 in human brain, while drug–gene interaction analysis suggested that ABCC2 interacts with oxcarbazepine and carbamazepine. Significance: The rs717620 polymorphism influences ASM therapeutic responses by altering brain expression levels of ABCC2.

To explore non-food bioactive products for pesticide candidates, and high value-added application of crop plants in agriculture, by using osthole (a natural coumarin isolated from a Chinese herbal medicine Cnidium monnieri) as a lead compound, a series of osthole derivatives containing oximoether groups were synthesized, and evaluated for their agricultural activities against Tetranychus cinnabarinus and Mythimna separata. The key steric configurations of eight derivatives were confirmed by X-ray crystallography. Especially compound 4r showed potential insecticidal activity (>2-fold of osthole) against M. separata, and 4g displayed good acaricidal activity against T. cinnabarinus (LC50 = 0.566 mg/mL, > 2-fold of osthole). Their structure–activity relationships were also concluded. It will pave the way for future application of osthole derivatives as coumarin-kind botanical pesticides in crop protection.

Background: Acne vulgaris (AV) is a common inflammatory skin disease. Although various mechanisms have been indicated in the etiopathogenesis of AV, the exact pathophysiology remains unknown. Various lasers have been used to treat AV; however, the serum level changes of inflammatory cytokines after laser therapy have not been elucidated. We aimed to investigate the relationship between inflammatory changes and remission on the opposite side in patients with moderate to severe AV after treating half of the face with 595- and 1 064-nm dual-wavelength laser. Methods: In total, 18 patients (9 male and 9 female) between 16 and 35 years of age with moderate to severe AV were evaluated in the study. Disease severity was classified according to the Pillsbury grading system of acne. Patients were randomized to receive a series of two treatment sessions at intervals of 2 weeks and followed up at 2 weeks after the final treatment. A 3 ​mL blood sample was drawn from every subject each time, and serum levels of inflammatory cytokines such as interleukin (IL)-6, IL-8, and IL-22 were determined using enzyme-linked immunosorbent assay at baseline and 2 weeks after each treatment. Improvement was determined by a blinded assessment of photographs taken before and after the final evaluation. Results: Inflammation was significantly reduced on both the treated and untreated sides, and symptoms of AV lesions were alleviated. All patients showed a significant increase in serum IL-22 levels after the first laser therapy, with no significant difference in serum IL-6 and IL-8 levels. After the second laser therapy, serum IL-6, IL-8, and IL-22 levels were significantly decreased. No significant side effects such as bruising, edema, hyperpigmentation, hypopigmentation, or scarring were reported. Conclusion: Half-face treatment with 595- and 1 064-nm dual-wavelength laser for moderate and severe AV showed a significant effect of full-face remission, which was associated with a gradual decrease in IL-6, IL-8, and IL-22 levels after half-face topical treatment. This suggests that reducing inflammatory cytokine levels in the serum can relieve inflammation in non-therapeutic sites. This laser treatment is effective, economical, and painless.

Abstract Larch, a widely distributed tree in boreal Eurasia, is experiencing rapid warming across much of its distribution. A comprehensive assessment of growth on warming is needed to comprehend the potential impact of climate change. Most studies, relying on rigid calendar-based temperature series, have detected monotonic responses at the margins of boreal Eurasia, but not across the region. Here, we developed a method for constructing temporally flexible and physiologically relevant temperature series to reassess growth-temperature relations of larch across boreal Eurasia. Our method appears more effective in assessing the impact of warming on growth than previous methods. Our approach indicates widespread and spatially heterogeneous growth-temperature responses that are driven by local climate. Models quantifying these results project that the negative responses of growth to temperature will spread northward and upward throughout this century. If true, the risks of warming to boreal Eurasia could be more widespread than conveyed from previous works.

Abstract Purpose To evaluate the value of MRI T1 mapping with Gd-EOB-DTPA for assessing liver function. Methods Seventy-two patients who underwent Gd-EOB-DTPA-enhanced MRI for focal liver lesions at Beijing Friendship Hospital from August 2020 to March 2022 were prospectively enrolled, and variable-flip-angle T1 mapping was performed before and 20 min after enhancement. The Child–Pugh (C-P) score and albumin-bilirubin (ALBI) grade of liver function were assessed using the clinical data of the patients. Correlation analysis was used to evaluate the correlation between T1 mapping parameters and liver function grading and laboratory tests. Nonparametric tests were used to compare the differences among different liver function groups. The liver function classification efficiency of each image index was evaluated with receiver operating characteristic (ROC) curves. Results T1post was positively correlated with the C-P grade and the ALBI grade (r = 0.717 and r = 0.652). ΔT1 was negatively correlated with the C-P grade and the ALBI grade (r = -0.790 and r = -0.658). T1post and ΔT1 significantly differed among different liver function grades (p

The skin of Takifugu obscurus is high in collagen. There is a growing trend to study the preparation method and functional properties of fish skin collagen due to the additive values. This research aimed to optimize the collagen extraction processing from the skin of dark-striped pufferfish including the effects of pepsin enzyme addition, enzymatic hydrolysis time, ultrasonic power and ultrasonic time. The dextran gel column chromatography method was used to separate and identify the extracted and salt-desorized collagen. The inhibitory activity of extracted collagen on tyrosinase and hyaluronase was studied. Results showed that, the best extraction rate of collagen was 71.6%±2.7% at pepsin 4.2%, enzymatic hydrolysis time 38 h, ultrasonic power 320 W, and the ultrasonic time 9 mins. The inhibition rate of tyrosinase and hyaluronidase was 85% and 90% respectively, at concentration of Takifugu obscurus skin collagen was 0.8 mg/mL and the pH was 5.5, which performed better than the commercial fish skin collagen. This study indicated that the skin collagen of Takifugu obscurus had the great potential in whitening and anti-inflammatory application, which could be further applied in the field of cosmetics.

Abstract Background Prediction of locoregional treatment response is important for further therapeutic strategy in patients with hepatocellular carcinoma. This study aimed to investigate the role of MRI-based radiomics and nomogram for predicting the outcome of locoregional treatment in patients with hepatocellular carcinoma. Methods The initial postoperative MRI after locoregional treatment in 100 patients with hepatocellular carcinoma was retrospectively analysed. The outcome was evaluated according to mRECIST at 6 months. We delineated the tumour volume of interest on arterial phase, portal venous phase and T2WI. The radiomics features were selected by using the independent sample t test or nonparametric Mann‒Whitney U test and the least absolute shrinkage and selection operator. The clinical variables were selected by using univariate analysis and multivariate analysis. The radiomics model and combined model were constructed via multivariate logistic regression analysis. A nomogram was constructed that incorporated the Rad score and selected clinical variables. Results Fifty patients had an objective response, and fifty patients had a nonresponse. Nine radiomics features in the arterial phase were selected, but none of the portal venous phase or T2WI radiomics features were predictive of the treatment response. The best radiomics model showed an AUC of 0.833. Two clinical variables (hCRP and therapy method) were selected. The AUC of the combined model was 0.867. There was no significant difference in the AUC between the combined model and the best radiomics model (P = 0.573). Decision curve analysis demonstrated the nomogram has satisfactory predictive value. Conclusions MRI-based radiomics analysis may serve as a promising and noninvasive tool to predict outcome of locoregional treatment in HCC patients, which will facilitate the individualized follow-up and further therapeutic strategies guidance.

Abstract Luminescence clusters composed of organic ligands and metals have gained significant interests as scintillators owing to their great potential in high X-ray absorption, customizable radioluminescence, and solution processability at low temperatures. However, X-ray luminescence efficiency in clusters is primarily governed by the competition between radiative states from organic ligands and nonradiative cluster-centered charge transfer. Here we report that a class of Cu4I4 cubes exhibit highly emissive radioluminescence in response to X-ray irradiation through functionalizing biphosphine ligands with acridine. Mechanistic studies show that these clusters can efficiently absorb radiation ionization to generate electron-hole pairs and transfer them to ligands during thermalization for efficient radioluminescence through precise control over intramolecular charge transfer. Our experimental results indicate that copper/iodine-to-ligand and intraligand charge transfer states are predominant in radiative processes. We demonstrate that photoluminescence and electroluminescence quantum efficiencies of the clusters reach 95% and 25.6%, with the assistance of external triplet-to-singlet conversion by a thermally activated delayed fluorescence matrix. We further show the utility of the Cu4I4 scintillators in achieving a lowest X-ray detection limit of 77 nGy s−1 and a high X-ray imaging resolution of 12 line pairs per millimeter. Our study offers insights into universal luminescent mechanism and ligand engineering of cluster scintillators.

Abstract The Belt and Road (B&R) Initiative is considered as closely aligned with the UN’s Sustainable Development Goals by 2030 and could have a huge global impact. Its sustainable development issues have attracted worldwide attention. However, both the existing research and data accumulation on this aspect are seriously insufficient. Starting from the logic of the ultimate goal of sustainable development (namely within the ecological limitations, maximizing human well-being with minimum ecological consumption and minimizing the planetary pressures with maximum resource utilization efficiency), we have constructed a comprehensive evaluation method on sustainable development, namely the Consumption-Pressure-Output-Efficiency method in our previous study. Based on it, we provide a database with five datasets, which includes four core datasets (ecological consumption, planetary pressures, human well-being outputs and ecological well-being output efficiency) and a related dataset (biocapacity, ecological surplus/deficit, population), covering 61 B&R countries, B&R regional average and global average from 1990 to 2018. It can be used for further comprehensive research on sustainable development under planetary pressures and others of B&R.

Abstract Continuous de novo fatty acid synthesis is required for the biosynthetic demands of tumor. FBXW7 is a highly mutated gene in CRC, but its biological functions in cancer are not fully characterized. Here, we report that FBXW7β, a FBXW7 isoform located in the cytoplasm and frequently mutated in CRC, is an E3 ligase of fatty acid synthase (FASN). Cancer-specific FBXW7β mutations that could not degrade FASN can lead to sustained lipogenesis in CRC. COP9 signalosome subunit 6 (CSN6), an oncogenic marker of CRC, increases lipogenesis via interacting with and stabilizing FASN. Mechanistic studies show that CSN6 associates with both FBXW7β and FASN, and antagonizes FBXW7β’s activity by enhancing FBXW7β autoubiquitination and degradation, which in turn prevents FBXW7β-mediated FASN ubiquitination and degradation, thereby regulating lipogenesis positively. Both CSN6 and FASN are positively correlated in CRC, and CSN6-FASN axis, regulated by EGF, is responsible for poor prognosis of CRC. The EGF-CSN6-FASN axis promotes tumor growth and implies a treatment strategy of combination of orlistat and cetuximab. Patient-derived xenograft experiments prove the effectiveness of employing orlistat and cetuximab combination in suppressing tumor growth for CSN6/FASN-high CRC. Thus, CSN6-FASN axis reprograms lipogenesis to promote tumor growth and is a target for cancer intervening strategy in CRC.

Abstract Limited numbers of available hematopoietic stem cells (HSCs) limit the widespread use of HSC-based therapies. Expansion systems for functional heterogenous HSCs remain to be optimized. Here, we present a convenient strategy for human HSC expansion based on a biomimetic Microniche. After demonstrating the expansion of HSC from different sources, we find that our Microniche-based system expands the therapeutically attractive megakaryocyte-biased HSC. We demonstrate scalable HSC expansion by applying this strategy in a stirred bioreactor. Moreover, we identify that the functional human megakaryocyte-biased HSCs are enriched in the CD34+CD38-CD45RA-CD90+CD49f lowCD62L-CD133+ subpopulation. Specifically, the expansion of megakaryocyte-biased HSCs is supported by a biomimetic niche-like microenvironment, which generates a suitable cytokine milieu and supplies the appropriate physical scaffolding. Thus, beyond clarifying the existence and immuno-phenotype of human megakaryocyte-biased HSC, our study demonstrates a flexible human HSC expansion strategy that could help realize the strong clinical promise of HSC-based therapies.

Abstract Background Neuroanatomical alterations have been associated with cognitive deficits in mild traumatic brain injury (MTBI). However, most studies have focused on the abnormal gray matter volume in widespread brain regions using a cross-sectional design in MTBI. This study investigated the neuroanatomical restoration of key regions in salience network and the outcomes in MTBI. Methods Thirty-six MTBI patients with posttraumatic headache (PTH) and 34 matched healthy controls were enrolled in this study. All participants underwent magnetic resonance imaging scans and were assessed with clinical measures during the acute and subacute phases. Surface-based morphometry was conducted to get cortical thickness (CT) and cortical surface area (CSA) of neuroanatomical regions which were defined by the Desikan atlas. Then mixed analysis of variance models were performed to examine CT and CSA restoration in patients from acute to subacute phase related to controls. Finally, mediation effects models were built to explore the relationships between neuroanatomical restoration and symptomatic improvement in patients. Results MTBI patients with PTH showed reduced headache impact and improved cognitive function from the acute to subacute phase. Moreover, patients experienced restoration of CT of the left caudal anterior cingulate cortex (ACC) and left insula and cortical surface area of the right superior frontal gyrus from acute to subacute phase. Further mediation analysis found that CT restoration of the ACC and insula mediated the relationship between reduced headache impact and improved cognitive function in patients. Conclusions These results showed that neuroanatomical restoration of key regions in salience network correlated reduced headache impact with cognitive function improvement in MTBI with PTH, which further substantiated the vital role of salience network and provided an alternative clinical target for cognitive improvement in MTBI patients with PTH. Graphical Abstract

At present, clinical interventions for chronic kidney disease are very limited, and most patients rely on dialysis to sustain their lives for a long time. However, studies on the gut–kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease. This study showed that berberine, a natural drug with low oral availability, significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins, including p-cresol. Furthermore, berberine reduced the content of p-cresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine–p-cresol pathway of the intestinal flora. Meanwhile, berberine increased the butyric acid producing bacteria and the butyric acid content in feces, while decreased the renal toxic trimethylamine N-oxide. These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut–kidney axis.

Abstract Background Gastric cancer (GC) is one of the most common malignant tumors of the digestive tract which seriously endangers the health of human beings worldwide. Transcriptomic deregulation by epigenetic mechanisms plays a crucial role in the heterogeneous progression of GC. This study aimed to investigate the impact of epigenetically regulated genes on the prognosis, immune microenvironment, and potential treatment of GC. Results Under the premise of verifying significant co-regulation of the aberrant frequencies of microRNA (miRNA) correlated (MIRcor) genes and DNA methylation-correlated (METcor) genes. Four GC molecular subtypes were identified and validated by comprehensive clustering of MIRcor and METcor GEPs in 1521 samples from five independent multicenter GC cohorts: cluster 1 was characterized by up-regulated cell proliferation and transformation pathways, with good prognosis outcomes, driven by mutations, and was sensitive to 5-fluorouracil and paclitaxel; cluster 2 performed moderate prognosis and benefited more from apatinib and cisplatin; cluster 3 was featured by an up-regulated ligand–receptor formation-related pathways, poor prognosis, an immunosuppression phenotype with low tumor purity, resistant to chemotherapy (e.g., 5-fluorouracil, paclitaxel, and cisplatin), and targeted therapy drug (apatinib) and sensitive to dasatinib; cluster 4 was characterized as an immune-activating phenotype, with advanced tumor stages, benefit more from immunotherapy and displayed worst prognosis. Conclusions According to the epigenetically regulated GEPs, we developed four robust GC molecular subtypes, which facilitated the understanding of the epigenetic mechanisms underlying GC heterogeneity, offering an optimized decision-making and surveillance platform for GC patients.

Abstract Background To evaluate the value of a deep learning-based computer-aided diagnostic system (DL-CAD) in improving the diagnostic performance of acute rib fractures in patients with chest trauma. Materials and methods CT images of 214 patients with acute blunt chest trauma were retrospectively analyzed by two interns and two attending radiologists independently firstly and then with the assistance of a DL-CAD one month later, in a blinded and randomized manner. The consensusdiagnosis of fib fracture by another two senior thoracic radiologists was regarded as reference standard. The rib fracture diagnostic sensitivity, specificity, positive predictive value, diagnostic confidence and mean reading time with and without DL-CAD were calculated and compared. Results There were 680 rib fracture lesions confirmed as reference standard among all patients. The diagnostic sensitivity and positive predictive value of interns weresignificantly improved from (68.82%, 84.50%) to (91.76%, 93.17%) with the assistance of DL-CAD, respectively. Diagnostic sensitivity and positive predictive value of attendings aided by DL-CAD (94.56%, 95.67%) or not aided (86.47%, 93.83%), respectively. In addition, when radiologists were assisted by DL-CAD, the mean reading time was significantly reduced, and diagnostic confidence was significantly enhanced. Conclusions DL-CAD improves the diagnostic performance of acute rib fracture in chest trauma patients, which increases the diagnostic confidence, sensitivity, and positive predictive value for radiologists. DL-CAD can advance the diagnostic consistency of radiologists with different experiences.

Abstract Clinical diagnosis has high requirements for the resolution of medical images, but most existing medical images super‐ resolution (SR) methods are performed under a known or specific degradation kernel. However, the difference between the actual degradations and their assumed degradation kernels results in a severe performance drop for the advanced SR methods in real applications. This paper proposes a medical image blind super‐resolution model (Med‐BSR) based on an improved degradation process to handle this issue. The model makes each of the degradation factors in medical image blind SR, such as blur, noise, and downsampling, more complex and practical. Specifically, the authors use the random select/combine strategy to randomly arrange and combine the type and order of each degradation factor, which significantly expands the degradation space. The authors also improved the loss function of the primary enhanced super‐resolution generative adversarial networks (ESRGAN) network. The extensive experimental results demonstrate that the authors’ designed model can accurately restore the natural degradation process, which can reconstruct high‐quality SR medical images. It also has a good generalization ability to realistic images simultaneously.

Purslane (Portulaca oleracea L.) is widely distributed and commonly utilized as an important medicinal food plant. The application of organic matter is a frequently employed strategy to enhance the quality and growth of medicinal plants. However, there is limited research on the impact of low-molecular-weight organic carbon on medicinal plants. This study evaluated the influence of the residue after evaporation (RAE) from industrial fermentation of vitamin C (L-ascorbic acid, ASA), which mainly consists of low-molecular-weight organic acids (LMWOAs), on the growth and bioactive constituents of purslane. Cultivation with different doses (2.7, 1.35, and 0.675 mL RAE per kg of soil) of RAE exhibited the highest levels of enhancement in the ASA, dopamine, total alkaloids, and total phenols content by 103.28%, 118.38%, 32.43%, and 27.64%, respectively, while promoting purslane’s growth. Furthermore, there was a dose–effect relationship between the dose of RAE and purslane’s ASA, total phenols, dopamine and total alkaloids. Metabolomic analysis revealed that the effects of RAE on pathways related to ASA synthesis, glycolysis, citrate cycle and amino acid synthesis contributed to the bioactive constituent accumulation in purslane. These findings suggest that RAE can effectively modulate the primary metabolic processes, thereby enhancing the yield and bioactive constituents of purslane. It is a valuable source of LMWOAs for the cultivation of medicinal plants. The resource utilization of RAE will enhance the production of medicinal plants, thereby contributing to satisfying the demand for bioactive natural products in the pharmaceutical, cosmetic, and food industries.

The relationship between type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC) has long been extensively recognized, but their crosstalk mechanisms based on gene regulation remain elusive. In our study, for the first time, bulk RNA-seq and single-cell RNA-seq data were used to explore the shared molecular mechanisms between T2DM and CRC. Moreover, Connectivity Map and molecular docking were employed to determine potential drugs targeting the candidate targets. Eight genes (EVPL, TACSTD2, SOX4, ETV4, LY6E, MLXIPL, ENTPD3, UGP2) were identified as characteristic comorbidity genes for T2DM and CRC, with EVPL and ENTPD3 further identified as core comorbidity genes. Our results demonstrated that upregulation of EVPL and downregulation of ENTPD3 were intrinsic molecular features throughout T2DM and CRC and were significantly associated with immune responses, immune processes, and abnormal immune landscapes in both diseases. Single-cell analysis highlighted a cancer-associated fibroblast (CAF) subset that specifically expressed ENTPD3 in CRC, which exhibited high heterogeneity and unique tumor-suppressive features that were completely different from classical cancer-promoting CAFs. Furthermore, ENTPD3+ CAFs could notably predict immunotherapy response in CRC, holding promise to be an immunotherapy biomarker at the single-cell level. Finally, we identified that droperidol may be a novel drug simultaneously targeting EVPL and ENTPD3. In conclusion, previous studies have often focused solely on metabolic alterations common to T2DM and CRC. Our study establishes EVPL and ENTPD3 as characteristic molecules and immune biomarkers of comorbidity in T2DM and CRC patients, and emphasizes the importance of considering immunological mechanisms in the co-development of T2DM and CRC.

Conventional straight fin (SF) radiators have difficulties meeting the cooling requirements of high-power electronic components. Therefore, based on the structure and technology of the detachable fin radiator, this paper proposes a kind of radiator embedded in the heat pipe base and uses the roll-bond flat heat pipe (RBFHP) to replace the traditional fin. The radiator has the advantages of modularity, easy manufacturing, low cost and good heat balance. In this study, the heat pipes (HPs)-RBFHPs radiator was tested in natural convection and forced convection to mimic the actual application scenario and compared with the conventional aluminum radiator. Heating power, angle, wind speed and other aspects were studied. The results showed that the cooling performance of the HPs-RBFHPs radiator was improved by 10.7% to 55% compared with that of the SF radiator under different working conditions. The minimum total thermal resistance in the horizontal state was only 0.37 °C/W. The temperature equalization of the base played a dominant role in the performance of the radiator at a large angle, and the fin group could be ineffective when the angle was greater than 60°. Under the most economical conditions with an inclination of 0° and a wind speed of 2 m/s, the input power was 340 W, the heat source temperature of the HPs-RBFHPs was only 64.2 °C, and the heat dissipation performance was 55.4% higher than that of SFs.

This work aimed to develop organic photocatalysts (PCs) that could mediate organocatalytic atom transfer radical polymerization (O-ATRP) under visible light. Through the core-modification of known chromophoric structures and ring-locking to reach a conjugation extension, annulated N-aryl benzo[kl]acridines were identified as effective visible light-responsive photocatalysts. The corresponding selenium-doped structure showed excellent performance in the O-ATRP of methacrylates, which could afford polymer products with controlled molecular weights and low dispersities under the irradiation of visible light at a 100 ppm catalyst loading.

The newly identified Sanghuangporus alpinus species of the Sanghuang mushroom genus has been found to possess significant medical benefits. However, the current artificial cultivation technology has not reached the requisite maturity. The response-surface methodology (RSM) was used to optimize the Sanghuangporus alpinus culture medium formulation and evaluate the functional activity of S. alpinus exopolysaccharides. First, a single-factor experiment was conducted to screen for optimal carbon and nitrogen sources for S. alpinus. Then, using Box–Behnken’s central composite design, a response-surface experiment was conducted to determine optimal culture parameters. Finally, the rationality of those parameters was assessed in a shaking flask experiment. The optimal culture parameters, determined through regression analysis, were 20.20 ± 0.17 g/L fructose (carbon source), 7.29 ± 0.10 g/L yeast extract (nitrogen source), and 0.99 ± 0.01 g/L dandelion. With optimization, the S. alpinus yield increased to 12.79 ± 1.41 g/L, twice that obtained from the initial culture medium. The S. alpinus exopolysaccharide exhibited an excellent antioxidant capacity, with the strongest scavenging effect noted on ABTS free radicals (lowest half-inhibitory concentration: 0.039 mg/mL). Additionally, this exopolysaccharide effectively inhibited various cancer cells, exhibiting the strongest activity against human glioma cells U251 (half-inhibitory concentration: 0.91 mg/mL). The RSM used to optimize the fermentation culture parameters of S. alpinus significantly increased the mycelial biomass. The improvement of Sanghuangporus alpinus yield through liquid fermentation and optimizing the fermentation medium could fill the existing gap in the cultivation of Sanghuangporus alpinus, as well as provide valuable data for the large-scale production of S. alpinus.

Residual pesticides in Agrocybe aegerita mushroom have emerged as a significant concern and bring much uncertainty due to processing procedures. In this study, a modified QuEChERS sample preparation procedure and UPLC-MS/MS were used to analyze the residual levels of four commonly used pesticides in A. aegerita from field to product processing. The field results showed that dissipation of these targeted chemicals was consistent with the first-order kinetics, and the half-life time ranged from 20.4 h to 47.6 h. The terminal residues of the four pesticides at harvest time ranged from 9.81 to 4412.56 μg/kg in raw mushroom. The processing factors (PFs) of clothianidin, diflubenzuron, chlorbenzuron, and pyridaben ranged from 0.119 to 0.808 for the drying process and from 0.191 to 1 for the washing process. By integrating the data from the field trials, the PFs, and the consumption survey, the chronic dietary risks of the target chemicals via A. aegerita intake ranged from 2.41 × 10−5 to 5.69 × 10−2 for children and from 6.34 × 10−6 to 1.88 × 10−2 for adults, which are considerably below the threshold of 1, indicating no unacceptable risk to consumers in the Fujian province of China. This research offers foundational data for appropriate use and the maximum residue limit (MRL) establishment for these four insecticides in A. aegerita.

Knowledge of the responses of winter wheat yield to meteorological dryness/wetness variations is crucial for reducing yield losses in Henan province, China’s largest winter wheat production region, under the background of climate change. Data on climate, yield and atmospheric circulation indices were collected from 1987 to 2017, and monthly self-calibrating Palmer drought severity index (sc-PDSI) values were calculated during the winter wheat growing season. The main results were as follows: (1) Henan could be partitioned into four sub-regions, namely, western, central-western, central-northern and eastern regions, based on the evolution characteristics of the time series of winter wheat yield in 17 cities during the period of 1988–2017. Among them, winter wheat yield was high and stable in the central-northern and eastern regions, with a remarkable increasing trend (p < 0.05). (2) The sc-PDSI in February had significantly positive impacts on climate-driven winter wheat yield in the western and central-western regions (p < 0.05), while the sc-PDSI in December and the sc-PDSI in May had significantly negative impacts on climate-driven winter wheat yield in the central-northern and eastern regions, respectively (p < 0.05). (3) There were time-lag relationships between the sc-PDSI for a specific month and the atmospheric circulation indices in the four sub-regions. Furthermore, we constructed multifactorial models based on selected atmospheric circulation indices, and they had the ability to simulate the sc-PDSI for a specific month in the four sub-regions. These findings will provide scientific references for meteorological dryness/wetness monitoring and risk assessments of winter wheat production.

Sanghuangporus sanghuang is a rare fungus growing on mulberry trees that has immense medicinal value. This study aimed to optimize the liquid-fermentation-media formulation and culture conditions for large-scale culturing of S. sanghuang by performing one-way testing and response surface methodology. The antioxidant and anticancer activities of the extracellular polysaccharides from S. sanghuang were also analyzed. The optimal formulation and growth conditions for S. sanghuang were as follows: glucose, 30.2 ± 0.37 g/L; yeast extract, 14.60 ± 0.05 g/L; dandelion powder, 1.24 ± 0.01 g/L; shaker speed, 150 r/min; and temperature, 25 °C. We obtained 13.99 ± 0.42 g/L of mycelium biomass by culturing S. sanghuang for 15 days with the optimized formulation. This was 2-fold higher than the mycelial mass obtained with the sub-optimal formulation. The extracellular fungal polysaccharides showed significant antioxidant activity against ABTS and DPPH free radicals, and significantly reduced the in vitro growth and survival of several cancer cell lines. The anticancer activity of the extracellular fungal polysaccharides was significantly higher in the human glioma cells than in other cancer cell lines. In summary, this study optimized the liquid media formulation and conditions for the large-scale culturing of S. sanghuang. Furthermore, the extracellular polysaccharides from S. sanghuang showed significant antioxidant and anticancer activities.

Owing to the variable shapes, large size difference, uneven grayscale, and dense distribution among biological cells in an image, it is very difficult to accurately detect and segment cells. Especially, it is a serious challenge for some microscope imaging devices with limited resources owing to a large number of learning parameters and computational burden when using the standard Mask R-CNN. In this work, we propose a mask R-DHCNN for cell detection and segmentation. More specifically, Dilation Heterogeneous Convolution (DHConv) is proposed by designing a novel convolutional kernel structure (i.e., DHConv), which integrates the strengths of the heterogeneous kernel structure and dilated convolution. Then, the traditional homogeneous convolution structure of the standard Mask R-CNN is replaced with the proposed DHConv module to it adapt to shape and size differences encountered in cell detection and segmentation tasks. Finally, a series of comparison and ablation experiments are conducted on various biological cell datasets (such as U373, GoTW1, SIM+, and T24) to verify the effectiveness of the proposed method. The results show that the proposed method can obtain better performance than some state-of-the-art methods in multiple metrics (including AP, Precision, Recall, Dice, and PQ) while maintaining competitive FLOPs and FPS.

Abstract Enhancing charge separation in semiconductor photocatalysts is a major challenge for efficient artificial photosynthesis. Herein, a compact heterojunction is designed by embedding half‐metallic C(CN)3 (hm‐CN) hydrothermally in BiOBr (BOB) as the backbone. The interface between hm‐CN and BOB is seamless and formed by covalent bonding to facilitate the transmission of photoinduced electrons from BOB to hm‐CN. The transient photocurrents and electrochemical impedance spectra reveal that the modified composite catalyst exhibits a larger electron transfer rate. The photocatalytic activity of hm‐CN/BOB increases significantly as indicated by a CO yield that is about four times higher than that of individual components. Density‐functional theory calculations verify that the heterojunction improves electron transport and decreases the reaction energy barrier, thus promoting the overall photocatalytic CO2 conversion efficiency. The half‐metal nitride coupled semiconductor heterojunctions might have large potential in artificial photosynthesis and related applications.

The substantial emissions of CO2 greenhouse gases have resulted in severe environmental problems, and research on the implementation of semiconductor materials to minimize CO2 is currently a highly discussed subject. Effective separation of interface charges is a major challenge for efficient piezo-photocatalytic systems. Meanwhile, the ultrasmall-sized metal nanoclusters can shorten the distance of electron transport. Herein, we synthesized Au25(p-MBA)18 nanoclusters (Au25 NCs) modified red graphitic carbon nitride (RCN) nanocatalysts with highly exposed Au active sites by in-situ seed growth method. The loading of Au25 NCs on the RCN surface provides more active sites and creates a long-range ordered electric field. It allows for the direct utilization of the piezoelectric field to separate photogenerated carriers during photo-piezoelectric excitation. Based on the above advantages, the rate of CO2 reduction to CO over Au25 NCs/RCN (111.95 μmol g−1 h−1) was more than triple compared to that of pristine RCN. This paper has positive implication for further application of metal clusters loaded semiconductor for piezo-photocatalytic CO2 reduction.

Abstract High power efficiency and low efficiency roll‐off at practical luminance are two requirements for new‐generation energy‐saving lighting technologies, which are still bottlenecks of thermally activated delayed fluorescence (TADF) white organic light‐emitting diodes (WOLED), despite the advantages of TADF materials and devices in low cost and high sustainability. Herein, we developed a spiro phosphine oxide host named SSOXSPO, which can form multiple and multidirectional intermolecular hydrogen bonds (IHB). The resulted multilevel IHB network integrates long‐range ordered and short‐range disordered alignments for suppressing triplet‐polaron quenching (TPQ) and triplet‐triplet annihilation (TTA). Electronic characteristics of SSOXSPO matrix are further regulated, leading to the optimal exciton allocation through balancing energy and charge transfer. As consequence, using SSOXSPO as host, the single‐emissive‐layer TADF WOLEDs realized the record performance, including ultralow operation voltage as ∼4.0 V, power efficiency beyond fluorescent tube (70.1 lm W−1) and negligible external quantum efficiency roll‐off (3%) at 1000 nits for indoor lighting. This work demonstrates that multiple interplays supported by host matrixes in TADF WOLEDs can facilitate the synergistic effects of TADF emitters on 100% exciton utilization.

Background Chronic kidney disease (CKD) is closely associated with cardiovascular disease. We aimed to examine the association of Life's Essential 8 (LE8), the recently updated measurement of cardiovascular health, with the prevalence of CKD among US adults. Methods and Results This population‐based cross‐sectional study used data from the National Health and Nutrition Examination Survey from 2007 to 2018 and included adults aged ≥20 years. Multivariable logistic and restricted cubic spline models were used to assess the associations between LE8 and CKD. Among 24 960 participants, 4437 were determined to have CKD (weighted percentage, 14.11%). After the adjustment of potential confounders, higher LE8 scores were associated with reduced odds of CKD (odds ratio for each 10‐point increase, 0.79 [95% CI, 0.76–0.83]), and a nonlinear dose–response relationship was observed. Similar patterns were also identified in the associations of health behavior and health factor scores with CKD. Meanwhile, higher scores for blood glucose (odds ratio, for each 10‐point increase, 0.88 [95% CI, 0.87–0.90]) and blood pressure (odds ratio, for each 10‐point increase, 0.92 [95% CI, 0.91–0.94]) in the LE8 component are significantly associated with a lower prevalence of CKD. The inversed association of LE8 score and CKD was significantly stronger among middle‐aged, male, and coupled participants. Conclusions LE8 was negatively associated with the prevalence of CKD in a nonlinear fashion. Promoting adherence to optimal cardiovascular health levels may be beneficial to reduce the burden of CKD.

Abstract Catalytic asymmetric hydroboration of fluoroalkyl‐substituted alkenes is a straightforward approach to access chiral small molecules possessing both fluorine and boron atoms. However, enantioselective hydroboration of fluoroalkyl‐substituted alkenes without fluorine elimination has been a long‐standing challenge in this field. Herein, a copper‐catalyzed hydroboration of difluoroalkyl‐substituted internal alkenes with high levels of regio‐ and enantioselectivities is reported. The native carbonyl directing group, copper hydride system, and bisphosphine ligand play crucial roles in suppressing the undesired fluoride elimination. This atom‐economic protocol provides a practical synthetic platform to obtain a wide scope of enantioenriched secondary boronates bearing the difluoromethylene moieties under mild conditions. Synthetic applications including functionalization of biorelevant molecules, versatile functional group interconversions, and preparation of difluoroalkylated Terfenadine derivative are also demonstrated.

BackgroundWith the continuous development of clinical medicine, an increasing number of non-pharmacological interventions have been applied for the treatment of knee osteoarthritis (KOA), with the results of several recent randomized controlled trials (RCTs) showing that a variety of externally-applied, non-pharmacological interventions (EANPI) can improve symptoms and inflammation in patients with KOA. However, the relative benefits and disadvantages of non-drug therapies remain uncertain, and an optimal treatment strategy has not yet been determined.ObjectiveThis study applied network meta-analysis (NMA) to compare and rank the effectiveness of EANPI on the short- and long-term clinical symptoms and inflammatory cytokine levels in patients with KOA.MethodsTwo independent researchers searched online databases and performed manual retrieval of related citations to identify RCTs that met the selection criteria for the network meta-analysis. These researchers retrieved studies indexed from database inception to August 2023 and performed data extraction and assessment of the risk of bias.ResultsThe analysis included 80 RCTs involving 8440 participants and nine externally-applied, non-pharmacological therapies, namely extracorporeal shock wave, radiofrequency, acupotomy, laser therapy, Tuina therapy, kinesio taping, electroacupuncture, platelet-rich plasma injection, and ozone therapy. The treatment courses ranged from 1 to 12 weeks, with follow-up periods ranging from 4 to 24 weeks. The results of the NMA indicated that each non-drug therapy was superior to sham intervention in improving all outcome indicators. Except for the visual analog scale (VAS) and Western Ontario MacMaster (WOMAC) pain outcomes, all non-drug therapies had better efficacy than pharmacological treatments. For short-term VAS and tumor necrosis factor-alpha (TNF-α), extracorporeal shock wave performed better than other therapies (90.2% and 85.2% respectively). Radiofrequency therapy may be the most promising method to reduce long-term VAS, short- and long-term WOMAC pain, and interleukin (IL)-1β level (84.8%, 97.8%, 90.1%, 94.8% respectively). Tuina therapy may be a significant choice for short- and long-term outcomes of WOMAC function and range of motion (ROM).ConclusionsThe results of the comprehensive comparison of the outcome indicators in 9 different EANPI indicated that radiofrequency and Tuina therapy were more effective and consistently ranked high in improving clinical symptoms in the short and long term. Radiofrequency is effective at relieving pain, and Tuina therapy can be given priority for treatment when hypofunction is the main symptom. EANPI to improve pain symptoms may be related to the regulation of inflammatory cytokine levels, which may be a potential mechanism of action.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?, identifier CRD42023464177.

ObjectiveRecent evidence indicates that cervical paraspinal muscle degeneration (PMD) is a prevalent and age-related condition in patients with cervical disc degenerative disease (CDDD). However, the relationship between surgery selection and post-operative outcomes in this population remains unclear. Consequently, this study aims to investigate the disparities in clinical outcomes, radiological findings, and complications between two frequently utilized anterior cervical surgical procedures. The objective is to offer guidance for the management of PMD in conjunction with CDDD.MethodsA total of 140 patients who underwent single-level anterior cervical discectomy and fusion (ACDF) at our department were included in this study. The patients were divided into three groups based on the severity of PMD: mild (n=40), moderate (n=54), and severe (n=46), as determined by Goutalier fat infiltration grade. The subjects of interest were those with moderate-severe PMD, and their clinical outcomes, radiological parameters, and complications were compared between those who received a stand-alone zero-profile anchored cage (PREVAIL) and those who received a plate-cage construct (PCC).ResultsThe JOA, NDI, and VAS scores exhibited significant improvement at all postoperative intervals when compared to baseline, and there were no discernible differences in clinical outcomes between the two groups. While the PCC group demonstrated more pronounced enhancements and maintenance of several sagittal alignment parameters, such as the C2-7 angle, FSU angle, C2-7 SVA, and T1 slope, there were no statistically significant differences between the two groups. The incidence of dysphagia in the zero-profile group was 22.41% at one week, which subsequently decreased to 13.79% at three months and 3.45% at the final follow-up. In contrast, the plate cage group exhibited a higher incidence of dysphagia, with rates of 47.62% at one week, 33.33% at three months, and 11.90% at the final follow-up. Notably, there were significant differences in the incidence of dysphagia between the two groups within the first three months. However, the fusion rate, occurrence of implant subsidence, and adjacent segment degeneration (ASD) were comparable at the final follow-up.ConclusionFor patients with one-level cervical disc degenerative disease combined with paraspinal muscle degeneration, both the zero-profile technique and PCC have demonstrated efficacy in ameliorating clinical symptoms and maintaining the postoperative sagittal balance. Although no significant disparities were observed between these two technologies in terms of complications such as adjacent segment degeneration and implant subsidence, the zero-profile technique exhibited superior performance over PCC in relation to dysphagia during the early stages of postoperative recovery. To validate these findings, studies with longer follow-up periods and evaluations of multilevel cervical muscles are warranted.

Background: Esophageal squamous carcinoma (ESCC) is one of the most malignant cancers in the world due to nodal metastasis. Therefore, a reasonable nodal staging system is extremely important for further treatment strategies. Recently the positive lymph node ratio (PLNR) is an important prognostic factor in various solid tumors Method: In this study, we investigated the clinical significance of the PLNR in stage II∼III ESCC patients. We collected the pathological characteristics of 272 stage II∼III ESCC patients from the SEER database from 2004–2016. ROC curves were used to calculate the best cutoff value of the PLNR; Pearson's Chi-square (χ2) and Fisher's exact probability tests were used to compare the clinical baseline and characteristics of patients. For continuous variables, Student's t-test and ANOVA were performed to evaluate statistical significance. Clinical outcomes were estimated by using the Kaplan‒Meier method and log-rank test. Furthermore, univariate and multivariate Cox regression models were utilized to analyze independent prognostic factors of ESCC patients. Results: Consequently, advanced ESCC patients were effectively stratified into two groups by prognosis using a PLNR cutoff value of 0.15 (P value = 0.04). The median survival time of patients with PLNR 45 mm (HR 1.32, 95 % CI 1.02–1.70), N stage (HR 1.41, 95 % CI 0.98–2.01) and PLNR ≥0.15 (HR 1.35, 95 % CI 0.87–1.74) were independent risk factors for prognostic prediction in ESCC patients. Meanwhile, 117 II∼III ESCC patients from Shaanxi Provincial People's Hospital shown that the overall survival with a PLNR

Objectives: Tuina is an effective complementary and alternative therapy. However, no bibliometric analysis has explored the global research status and emerging trends of tuina. Therefore, our study aimed to provide a perspective on the current state and frontier trends in the field. Design: Bibliometric analysis Setting: Tuina-related publications between January 1, 2003, and December 31, 2022, were obtained from the Web of Science Core Collection database. Main outcome measures: The knowledge graph software CiteSpace and VOSViewer were used to quantitatively analyse annual trends in annual publication volume, journals, countries, institutions, authors, cited references, and keywords. Results: Overall, 1877 articles were obtained. Consequently, the number of annual publications in tuina gradually increased. China published the most articles (1402 articles, 58.01%), followed by the Chinese Academy of Sciences (110 articles, 2.57%). Original and review articles were the two main types of publications. Photonics Research ranked first (101 articles, 5.38%) as the most influential affiliate and productive journal. These articles come from 8423 authors, among whom Min Fang published the most publications, and Ernst E was co-cited most often. According to the keyword co-occurrence analysis, the new research frontiers were meta-analyses. Conclusion: This comprehensive bibliometric study analysed the publications on tuina and presented them visually, revealing new research trends, pivotal points, research hotspots, and frontiers. Prospective strategies and potential directions for further studies were also provided.

Kabuki syndrome (KS) is a rare multisystem-affecting genetic disorder, and usually accompanied with autoimmune disorders such as immune thrombocytopenic purpura (ITP). Here, we report a 16-year-old patient with Kabuki syndrome with ITP and observe the therapeutic effect of TPO agonist hetrombopag olamine tablets. The duration of maintenance therapy and follow up were both 17 months. Whole exon sequencing (WES) of the patient’s peripheral blood showed c.5775_5778del (p. Leu1926LysfsTer120) heterozygous mutation in the KMT2D gene, which was not reported before.

Pigeon paramyxovirus 1 (PPMV-1) is an antigenic host variant of avian paramyxovirus 1. Sporadic outbreaks of PPMV-1 infection have occurred in pigeons in China; however, few cases of human PPMV-1 infection have been reported. The purpose of this article is to report a case of severe human PPMV-1 infection in an individual with probable post-COVID-19 syndrome (long COVID) who presented with rapidly progressing pulmonary infection. The patient was a 66-year-old man who was admitted to the intensive care unit 11 days after onset of pneumonia and recovered 64 days after onset. PPMV-1 was isolated from the patient’s sputum and in cloacal smear samples from domesticated pigeons belonging to the patient’s neighbour. Residual severe acute respiratory syndrome coronavirus 2 was detected in respiratory and anal swab samples from the patient. Sequencing analyses revealed that the PPMV-1 genome belonged to genotype VI.2.1.1.2.2 and had the 112RRQKRF117 motif in the cleavage site of the fusion protein, which is indicative of high virulence. This case of cross-species transmission of PPMV-1 from a pigeon to a human highlights the risk of severe PPMV-1 infection in immunocompromised patients, especially those with long COVID. Enhanced surveillance for increased risk of severe viral infection is warranted in this population.