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Abstract To investigate the impact of different 5ʹ untranslated regions (UTRs) on mRNA vaccine translation efficiency, five dual-reporter gene expression plasmids with different 5ʹUTRs were constructed. The corresponding mRNA transcripts were transcribed and capped in vitro. By comparing the expression levels of reporter genes with different 5ʹUTRs, we identified the 5ʹUTR associated with the highest expression level. Subsequently, HIVgp145 mRNA vaccines containing various 5ʹUTRs were constructed and verified. The results demonstrated that mRNA 3 (β-globin 5ʹUTR) displayed the greatest number of green fluorescence-positive cells and the highest luciferase fluorescence intensity in the reporter gene expression system. Further, among the HIVgp145 mRNA vaccines with different 5ʹUTRs, mRNA 7 (β-globin 5ʹUTR) exhibited the highest level of expression. These findings indicate that it is feasible to use the 5ʹUTR of β-globin in an mRNA vaccine, laying the foundation for animal immunogenicity testing.

Abstract Pipe contaminant detection holds considerable importance within various industries, such as the aviation, maritime, medicine, and other pertinent fields. This capability is beneficial for forecasting equipment potential failures, ascertaining operational situations, timely maintenance, and lifespan prediction. However, the majority of existing methods operate offline, and the detectable parameters online are relatively singular. This constraint hampers real-time on-site detection and comprehensive assessments of equipment status. To address these challenges, this paper proposes a sensing method that integrates an ultrasonic unit and an electromagnetic inductive unit for the real-time detection of diverse contaminants and flow rates within a pipeline. The ultrasonic unit comprises a flexible transducer patch fabricated through micromachining technology, which can not only make installation easier but also focus the sound field. Moreover, the sensing unit incorporates three symmetrical solenoid coils. Through a comprehensive analysis of ultrasonic and induction signals, the proposed method can be used to effectively discriminate magnetic metal particles (e.g., iron), nonmagnetic metal particles (e.g., copper), nonmetallic particles (e.g., ceramics), and bubbles. This inclusive categorization encompasses nearly all types of contaminants that may be present in a pipeline. Furthermore, the fluid velocity can be determined through the ultrasonic Doppler frequency shift. The efficacy of the proposed detection principle has been validated by mathematical models and finite element simulations. Various contaminants with diverse velocities were systematically tested within a 14 mm diameter pipe. The experimental results demonstrate that the proposed sensor can effectively detect contaminants within the 0.5−3 mm range, accurately distinguish contaminant types, and measure flow velocity.

Androgen deprivation therapy (ADT) has long been the only treatment for metastatic hormone-sensitive prostate cancer (mHSPC). In recent years, with the use of docetaxel chemotherapy and the emergence of various novel hormone therapy drugs, such as Abiraterone, Enzalutamide, Apalutamide, Darolutamide, and Rezvilutamide, the treatment strategies for mHSPC have been greatly changed. Furthermore, local treatment has been added to the treatment of low tumor burden mHSPC and triple therapy has been regarded as an important treatment choice for high tumor burden mHSPC. The survival rate of mHSPC patients has increased significantly and the quality of life also improved with these new treatment strategies. This article reviews the latest advances and controversies in the current treatment of mHSPC. Ongoing clinical trials are introduced and further directions are also discussed in this mini-review.

Phthalates (PAEs) are synthetic compounds extensively employed in consumer products. Blood pressure (BP) in children can vary, the degree of visit-to-visit BP variability (VVV) is at least partially independent of BP. The interactions between PAEs exposure, pubertal-related genetic susceptibility and lifestyles on childhood VVV are not investigated. This study utilized data from a cohort collected from Oct 2017–2020 in Xiamen, China. Seven urine PAE metabolites were measured. The long-term VVV was characterized employing the standard deviation (SD) and average real variability. We constructed a genetic risk score (GRS) of pubertal-related genes and healthy lifestyle scores. Exposed to high levels of mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) (OR=1.43, 95 %CI=1.07, 1.92) and mono-2-ethyl-5-oxohexyl phthalate (OR=1.36, 95 % CI=1.01, 1.83) was related to increased SBP-SD, and the OR for high SBP-SD related to high GRS was 1.38 (95 % CI=1.02, 1.85). Compared to participants who had low GRS and low MEHHP exposure, participants exhibiting high GRS and MEHHP levels were more likely to experience high SBP-SD (OR=2.00, P

Abstract Objective To evaluate the biomechanical characteristics of grafts from three different anterior cruciate ligament (ACL) reconstructive surgeries and to determine which method is better at restoring knee joint stability. Methods A 31-year-old female volunteer was enrolled in the study. According to the magnetic resonance imaging of her left knee, a three-dimensional model consisting of the distal femur, proximal tibia and fibula, ACL, posterior cruciate ligament, medial collateral ligament and lateral collateral ligament was established. Then, the ACL was removed from the original model to simulate the knee joint after ACL rupture. Based on the knee joint model without the ACL, single-bundle ACL reconstruction, double-bundle ACL reconstruction, and flat-tunnel ACL reconstruction were performed. The cross-sectional diameters of the grafts were equally set as 6 mm in the three groups. The bone tissues had a Young’s modulus of 17 GPa and a Poisson’s ratio of 0.36. The ligaments and grafts had a Young’s modulus of 390 MPa and a Poisson’s ratio of 0.4. Six probes were placed in an ACL or a graft to obtain the values of the equivalent stress, maximum principal stress, and maximum shear stress. After pulling the proximal tibia with a forward force of 134 N, the distance that the tibia moved and the stress distribution in the ACL or the graft, reflected by 30 mechanical values, were measured. Results The anterior tibial translation values were similar among the three groups, with the double-bundle ACL reconstruction group performing the best, followed closely by the patellar tendon ACL reconstruction group. In terms of stress distribution, 13 out of 30 mechanical values indicated that the grafts reconstructed by flat bone tunnels had better performance than the grafts in the other groups, while 12 out of 30 showed comparable outcomes, and 5 out of 30 had worse outcomes. Conclusion Compared with traditional single-bundle and double-bundle ACL reconstructions, flat-tunnel ACL reconstruction has advantages in terms of stress dispersion. Additionally, flat-tunnel ACL reconstruction falls between traditional double-bundle and single-bundle ACL reconstructions in terms of restoring knee joint stability and is superior to single-bundle ACL reconstruction.

Small for gestational age (SGA) children′s catch-up growth after birth has a significant impact on their future health outcomes. While there has been considerable research into the postnatal development and catch-up growth characteristics of SGA, studies on the health outcomes of such growth are relatively rare, and the conclusions vary, lacking a systematic summary. This study summarizes the research progress on the health outcomes of SGA catch-up growth from three aspects: physical development, metabolism, and neuropsychology. It also proposes hypotheses in order to provide a basis for the growth and targeted intervention of SGA.

Abstract Background Previously, we have demonstrated that the batch variations of human platelet lysate (conventional MSC expansion medium) induce MSC heterogeneity and therapeutic inconsistency. On the other hand, the MSCs expanded with chemical defined medium have improved therapeutic consistency. Methods In the current study, we studied the MSC subpopulation composition and variation in different types and batches of MSC expansion medium with scRNA-seq analysis. Results MSCs expanded with different batches of media have higher levels of heterogeneity from the perspective of cell subpopulation composition at transcriptome levels and therapeutic inconsistency. The CD317+ subpopulation has enhanced immune suppression activities. And the percentage of CD317+ MSCs within MSCs is tightly correlated with its immune suppression activities, and also contributes to the heterogeneity and therapeutic inconsistency of MSCs. the CD317+ MSCs have increased expression levels of PTX3, which might stabilize the TSG6 protein and improve the therapeutic effects Conclusions Thus, purifying CD317+ MSCs is one efficient strategy to reduce MSC heterogeneity and increase the therapeutic consistency of MSCs.

Neuroendocrine prostate cancer (NEPC) is a highly aggressive variant of castration-resistant prostate cancer. It is characterized by low or no expression of the androgen receptor (AR), activation of AR-independent signaling, and increased neuroendocrine phenotype. Most of NEPC is induced by treatment of androgen deprivation therapy and androgen receptor pathway inhibitors (ARPIs). Currently, the treatment of NEPC follows the treatment strategy for small-cell lung cancer, lacking effective drugs and specific treatment options. This review summarizes potential novel targets and therapies for NEPC treatment, including epigenetic regulators (zeste homolog 2 inhibitors, lysine-specific demethylase 1 inhibitors), aurora kinase A inhibitors, poly-ADP-ribose polymerase inhibitors, delta-like ligand 3 targeted therapies, a combination of immunotherapies, etc. Other promising targets and future directions are also discussed in this review. These novel targets and therapies may provide new opportunities for the treatment of NEPC.

Abstract Background Although both preclinical and clinical studies have shown the great application potential of MSCs (mesenchymal stem/stromal cells) in treating many kinds of diseases, therapeutic inconsistency resulting from cell heterogeneity is the major stumbling block to their clinical applications. Cell population diversity and batch variation in the cell expansion medium are two major inducers of MSC heterogeneity. Methods Cell population diversity was investigated through single-cell RNA sequencing analysis of human MSCs derived from the umbilical cord and expanded with fully chemically defined medium in the current study. Then, the MSC subpopulation with enhanced anti-inflammatory effects was studied in vitro and in vivo. Results Our data showed that MSCs contain different populations with different functions, including subpopulations with enhanced functions of exosome secretion, extracellular matrix modification and responses to stimuli (regeneration and immune response). Among them, CD317+ MSCs have improved differentiation capabilities and enhanced immune suppression activities. Underlying mechanism studies showed that higher levels of TSG6 confer enhanced anti-inflammatory functions of CD317+ MSCs. Conclusions Thus, CD317+ MSCs might be a promising candidate for treating immunological disorder-related diseases.

Abstract Animal species, encompassing both pollinators and herbivores, exhibit a preference for plants based on optimal foraging theory. Understanding the intricacies of these adaptive plant-animal interactions in the context of community assembly poses a main challenge in ecology. This study delves into the impact of adaptive interaction rewiring between species belonging to different guilds on the structure and stability of a 3-guild ecological network, incorporating both mutualistic and antagonistic interactions. Our findings reveal that adaptive rewiring results in sub-networks becoming more nested and compartmentalized. Furthermore, the rewiring of interactions uncovers a positive correlation between a plant’s generalism concerning both pollinators and herbivores. Additionally, there is a positive correlation between a plant’s degree centrality and its energy budget. Although network stability does not exhibit a clear relationship with non-random structures, it is primarily influenced by the balance of multiple interaction strengths. In summary, our results underscore the significance of adaptive interaction rewiring in shaping the structure of 3-guild networks. They emphasize the importance of considering the balance of multiple interactions for the stability of adaptive networks, providing valuable insights into the complex dynamics of ecological communities.

Objective: Real-word data on long-acting luteinizing hormone-releasing hormone (LHRH) agonists in Chinese patients with prostate cancer are limited. This study aimed to determine the real-world effectiveness and safety of the LHRH agonist, goserelin, particularly the long-acting 10.8-mg depot formulation, and the follow-up patterns among Chinese prostate cancer patients. Methods: This was a multicenter, prospective, observational study in hormone treatment-naïve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen. The patients had follow-up evaluations for 26 weeks. The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen (PSA) levels. The secondary outcomes included testosterone and PSA levels, attainment of chemical castration (serum testosterone

Abstract Background The relationship between lean body mass (LBM) and blood pressure (BP) is controversial and limited. This study investigated the associations between LBM indexes and BP in adults of different ages and with varying body fat distribution. Methods The data for the present analysis was obtained from a cross-sectional survey of 1,465 adults (50.7% males) aged 18–70 years conducted in Beijing, China. Regional LBM and fat distribution, including fat mass (FM) and android to gynoid fat ratio (AOI), were assessed using a dual-energy X-ray bone densitometer. Generalized Liner Model (GLM) was employed. Confounders, including age, sex, height, weight, smoking, and alcohol use, were evaluated through questionnaires and physical examinations. Results Males had higher rates of hypertension (11.19% vs. 4.92%) and prehypertension (21.57% vs. 14.59%) than females. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 122.04 mmHg and 76.68 mmHg. There were no significant associations between LBM and DBP (p > 0.05). However, arms LBM (β = 1.86, 95% CI: 0.77, 2.94) and trunk LBM (β = 0.37, 95% CI: 0.01, 0.73) were significantly associated with SBP. The association of LBM on DBP was stronger with increasing ages, and stronger in females than in males (p

Abstract A series of tests for time-delayed rockburst of granite under true triaxial condition was designed and carried out. By using the true triaxial rockburst test system, an acoustic emission (AE) system, a high-speed camera system, and a digital image motion analysis software, the time-delayed rockburst development process was monitored and studied. Four stages were found in the failure of granite time-delayed rockburst, i.e. grains ejection, slab breaks and ejects, first fragments ejection and second fragments ejection. There is a “V” shear crack generated in the time-delayed rockburst sample, and several tensile cracks in the lower part of the rock sample cross through the “V” shear crack. The longer the duration (the time elapsed between the moments the AE hits rises rapidly and the rockburst occurs), the smaller the depth of the rockburst pit. The time-delayed rockburst debris are mainly composed of blocks and fragments. The longer the duration, the smaller the total debris mass, the percentage of ejected debris and the ejection kinetic energy. The fractal dimension of the debris is positively correlated with the duration. The longer the duration, the higher the degree of fragmentation. The cracks generated are tensile-shear composite cracks. In the loading stage, it is dominated by shear cracks. However, in the time-lag stage, it is dominated by tensile cracks. With the increase of the duration, the proportion of tensile cracks increased and the proportion of shear cracks decreased. The research results will have a certain reference value for the warning and risk mitigation of time-delayed rockbursts.

Cadmium (Cd2+) is a non-essential and highly toxic element to all organic life forms, including plants and humans. In response to Cd stress, plants have evolved multiple protective mechanisms, such as Cd2+ chelation, vesicle sequestration, the regulation of Cd2+ uptake, and enhanced antioxidant defenses. When Cd2+ accumulates in plants to a certain level, it triggers a burst of reactive oxygen species (ROS), leading to chlorosis, growth retardation, and potentially death. To counteract this, plants utilize a complex network of enzymatic and non-enzymatic antioxidant systems to manage ROS and protect cells from oxidative damage. This review systematically summarizes how various elements, including nitrogen, phosphorus, calcium, iron, and zinc, as well as phytohormones such as abscisic acid, auxin, brassinosteroids, and ethylene, and signaling molecules like nitric oxide, hydrogen peroxide, and hydrogen sulfide, regulate the antioxidant system under Cd stress. Furthermore, it explores the mechanisms by which exogenous regulators can enhance the antioxidant capacity and mitigate Cd toxicity.

Background: Alternol is a small molecular compound isolated from the fermentation of a mutant fungus obtained from Taxus brevifolia bark. Our previous studies showed that Alternol treatment induced reactive oxygen species (ROS)-dependent immunogenic cell death. This study conducted a comprehensive investigation to explore the mechanisms involved in Alternol-induced immunogenic cell death.Methods: Prostate cancer PC-3, C4-2, and 22RV1 were used in this study. Alternol interaction with heat shock proteins (HSP) was determined using CETSA assay. Alternol-regulated ER stress proteins were assessed with Western blot assay. Extracellular adenosine triphosphate (ATP) was measured using ATPlite Luminescence Assay System.Results: Our results showed that Alternol interacted with multiple cellular chaperone proteins and increased their expression levels, including endoplasmic reticulum (ER) chaperone hypoxia up-regulated 1 (HYOU1) and heat shock protein 90 alpha family class B member 1 (HSP90AB1), as well as cytosolic chaperone heat shock protein family A member 8 (HSPA8). These data represented a potential cause of unfolded protein response (UPR) after Alternol treatment. Further investigation revealed that Alternol treatment triggered ROS-dependent (ER) stress responses via R-like ER kinase (PERK), inositol-requiring enzyme 1α (IRE1α). The double-stranded RNA-dependent protein kinase (PKR) but not activating transcription factor 6 (ATF6) cascades, leading to ATF-3/ATF-4 activation, C/EBP-homologous protein (CHOP) overexpression, and X-box binding protein XBP1 splicing induction. In addition, inhibition of these ER stress responses cascades blunted Alternol-induced extracellular adenosine triphosphate (ATP) release, one of the classical hallmarks of immunogenic cell death.Conclusion: Taken together, our data demonstrate that Alternol treatment triggered multiple ER stress cascades, leading to immunogenic cell death.

BackgroundAn accelerated epidemiological transition, spurred by economic development and urbanization, has led to a rapid transformation of the disease spectrum. However, this transition has resulted in a divergent change in the burden of infectious diseases between urban and rural areas. The objective of our study was to evaluate the long-term urban-rural disparities in infectious diseases among children, adolescents, and youths in China, while also examining the specific diseases driving these disparities.Methods and findingsThis observational study examined data on 43 notifiable infectious diseases from 8,442,956 cases from individuals aged 4 to 24 years, with 4,487,043 cases in urban areas and 3,955,913 in rural areas. The data from 2013 to 2021 were obtained from China's Notifiable Infectious Disease Surveillance System. The 43 infectious diseases were categorized into 7 categories: vaccine-preventable, bacterial, gastrointestinal and enterovirus, sexually transmitted and bloodborne, vectorborne, zoonotic, and quarantinable diseases. The calculation of infectious disease incidence was stratified by urban and rural areas. We used the index of incidence rate ratio (IRR), calculated by dividing the urban incidence rate by the rural incidence rate for each disease category, to assess the urban-rural disparity. During the nine-year study period, most notifiable infectious diseases in both urban and rural areas exhibited either a decreased or stable pattern. However, a significant and progressively widening urban-rural disparity in notifiable infectious diseases was observed. Children, adolescents, and youths in urban areas experienced a higher average yearly incidence compared to their rural counterparts, with rates of 439 per 100,000 compared to 211 per 100,000, respectively (IRR: 2.078, 95% CI [2.075, 2.081]; p < 0.001). From 2013 to 2021, this disparity was primarily driven by higher incidences of pertussis (IRR: 1.782, 95% CI [1.705, 1.862]; p < 0.001) and seasonal influenza (IRR: 3.213, 95% CI [3.205, 3.220]; p < 0.001) among vaccine-preventable diseases, tuberculosis (IRR: 1.011, 95% CI [1.006, 1.015]; p < 0.001), and scarlet fever (IRR: 2.942, 95% CI [2.918, 2.966]; p < 0.001) among bacterial diseases, infectious diarrhea (IRR: 1.932, 95% CI [1.924, 1.939]; p < 0.001), and hand, foot, and mouth disease (IRR: 2.501, 95% CI [2.491, 2.510]; p < 0.001) among gastrointestinal and enterovirus diseases, dengue (IRR: 11.952, 95% CI [11.313, 12.628]; p < 0.001) among vectorborne diseases, and 4 sexually transmitted and bloodborne diseases (syphilis: IRR 1.743, 95% CI [1.731, 1.755], p < 0.001; gonorrhea: IRR 2.658, 95% CI [2.635, 2.682], p < 0.001; HIV/AIDS: IRR 2.269, 95% CI [2.239, 2.299], p < 0.001; hepatitis C: IRR 1.540, 95% CI [1.506, 1.575], p < 0.001), but was partially offset by lower incidences of most zoonotic and quarantinable diseases in urban areas (for example, brucellosis among zoonotic: IRR 0.516, 95% CI [0.498, 0.534], p < 0.001; hemorrhagic fever among quarantinable: IRR 0.930, 95% CI [0.881, 0.981], p = 0.008). Additionally, the overall urban-rural disparity was particularly pronounced in the middle (IRR: 1.704, 95% CI [1.699, 1.708]; p < 0.001) and northeastern regions (IRR: 1.713, 95% CI [1.700, 1.726]; p < 0.001) of China. A primary limitation of our study is that the incidence was calculated based on annual average population data without accounting for population mobility.ConclusionsA significant urban-rural disparity in notifiable infectious diseases among children, adolescents, and youths was evident from our study. The burden in urban areas exceeded that in rural areas by more than 2-fold, and this gap appears to be widening, particularly influenced by tuberculosis, scarlet fever, infectious diarrhea, and typhus. These findings underscore the urgent need for interventions to mitigate infectious diseases and address the growing urban-rural disparity.

Abstract Background Phthalate esters (PAEs) are known to have hormone-like properties, and there is a growing trend of children expressing a gender identity different from assigned sex. However, there has been limited research in the potential links between PAEs exposure and gender identity. Methods A total of 571 children (278 boys) completed the follow-up from Oct 2017 to Oct 2020 in Childhood Blood Pressure and Environmental Factors (CBPEF) cohort in Xiamen, China. Urinary PAE metabolites were measured at three time of visits using ultraperformance liquid chromatography-tandem mass spectrometry. The Children’s Sex Role Inventory scale was used to assess gender identity (masculinity, femininity, androgyny and undifferentiated), and Tanner definition was used to define puberty timing. Generalized linear models and log-binomial regression were used to assess the relationships between PAEs exposure, gender trait scores and gender identity. Results Overall, the concentration of most PAEs in more than 90% of participants was above the limit of detection values. In visit 1, there were 10.1% boys with femininity and 11.3% girls with masculinity; while these figures increased to 10.8% and 12.3% during follow-up, respectively. Early puberty onset accounted for 24.8% and 25.6% among boys and girls. Long-term exposure to mono-2-ethylhexyl phthalate (MEHP) (β = 1.20, 95%CI = 0.13, 2.28), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) (β = 1.25, 95%CI = 0.22, 2.28) and mono-2-ethyl-5-oxohexyl phthalate (MEOHP) (β = 1.40, 95%CI = 0.24, 2.56) was associated with the increased differences of femininity trait scores in boys who enter puberty earlier, prolonged exposure to di(2-ethylhexyl) phthalate (DEHP) might also have such a positive impact (β = 1.38, 95%CI = 0.36, 2.41). For gender identity, persistent exposure to low molecular weight phthalates (LMWP) was negatively associated with undifferentiated type among boys entering puberty earlier (RR = 0.18, 95%CI = 0.05, 0.75, P 1 for their femininity. Conclusion Long-term exposure to PAEs increase the femininity trait scores in boys with early onset of puberty. Although the mechanisms remain to be determined, environmental pollution might have subtle, yet measurable effects on childhood gender identity. Reducing these chemicals exposure has important public implications on gender development.

Abstract Background This study investigated the role of apoptosis-related genes in thoracic aortic aneurysms (TAA) and provided more insights into TAA's pathogenesis and molecular mechanisms. Material/methods Two gene expression datasets (GSE9106 and GSE26155) were retrieved from the Gene Expression Omnibus (GEO) database. Apoptosis-related genes were obtained from the KEGG apoptosis pathway (hsa04210). Differentially expressed apoptosis-related genes were identified by performing differential expression analysis using limma for TAA blood and tissue samples. GO and KEGG enrichment analysis of the differentially expressed apoptosis genes was performed using the Metascape web tool. The miRNA-mRNA regulatory network was reconstructed using the ENCORI and miRDB databases, and functional enrichment analysis was performed on the related miRNAs using the miEAA tool. The correlation between the expression levels of differentially expressed apoptosis-related genes and genes involved in immune infiltration in TAA was calculated using the CIBERSORT algorithm. The apoptosis modification patterns mediated by differentially expressed apoptosis-related genes were systematically assessed in TAA samples. Results A total of 9 differentially-expressed apoptosis-related genes were identified in TAA samples compared with normal samples. 150 miRNAs and 6 mRNAs regulatory networks were reconstructed using the ENCORI and miRDB databases. Immune infiltration analysis revealed that the GZMB had the strongest positive correlation with activated NK cells and the DFFA presented the strongest positive correlation with T cells follicular helper. 3 distinct apoptosis modification patterns mediated by 9 differentially-expressed apoptosis-related genes were identified. They differ in immune characteristics and drug sensitivity, and their biological functions in these subtypes were further studied. Conclusions This study identified key apoptosis-related genes related to TAA and evaluated the modification patterns of key apoptosis genes in TAA, providing insights into potential targets and mechanisms of TAA pathogenesis and progression.

Abstract Background No consensus currently exists regarding the optimal protocol for repetitive transcranial magnetic stimulation (rTMS) treatment of upper-extremity motor dysfunction after stroke. Studies have shown that combined low- and high-frequency stimulation (LF-HF-rTMS) of the bilateral cerebral hemispheres is more effective than sham stimulation or stimulation of one cerebral hemisphere alone in treating motor dysfunction in the subacute stage of stroke. The efficacy of this protocol in the convalescence phase of stroke has rarely been reported, and its mechanism of action has not been clarified. In this study, we designed a prospective, single-blind, randomized controlled trial to investigate the efficacy and safety of different stimulation regimens for the treatment of upper extremity motor disorders in patients with convalescent stage stroke and aimed to explore the underlying mechanisms based on biomarkers such as brain-derived neurotrophic factor (BDNF). Methods Seventy-six subjects will be randomly divided into combined, low-frequency, high-frequency, and control groups based on the proportion of 1:1:1:1, with 19 cases in each group. All groups will have conventional rehabilitation, on top of which the combined group will receive 1 Hz rTMS in the unaffected hemisphere and 10 Hz rTMS in the affected hemisphere. The low-frequency group will be administered 1 Hz rTMS in the unaffected hemisphere and sham stimulation in the contralateral hemisphere. The high-frequency group will be administered 10 Hz rTMS in the affected hemisphere and contralateral sham stimulation. The control group will receive bilateral sham stimulation. Assessments will be performed at baseline, after 2 weeks of treatment, and at post-treatment follow-up at week 6. The primary outcomes are FMA-UE (Fugl-Meyer assessment-upper extremity), latency, and serum BDNF levels. The secondary outcomes are the National Institute of Health Stroke Scale (NIHSS), Brunnstrom staging (BS), modified Ashworth scale (MAS), Modified Barthel Index (MBI), central motor conduction time (CMCT), precursor proteins of mature BDNF (proBDNF), and matrix metalloproteinase-9 (MMP-9) levels. Adverse events, such as headaches and seizures, will be recorded throughout the study. Discussion The findings of this study will help develop optimal stimulation protocols for motor recovery in stroke patients and identify biomarkers that respond to post-stroke motor rehabilitation, for better guidance of clinical treatment. Trial registration The study protocol was passed by the Medical Research Ethics Committee of the General Hospital of Ningxia Medical University on January 1, 2022 (no. KYLL-2021–1082). It was registered into the Chinese Clinical Trials Registry on May 22, 2022 (no. ChiCTR2200060201). This study is currently in progress. Graphical Abstract

Abstract Alzheimer's disease (AD) is the most prevalent form of dementia, and it displays both clinical and molecular variability. RNA N6-methyladenosine (m6A) regulators are involved in a wide range of essential cellular processes. In this study, we aimed to identify molecular signatures associated with m6A in Alzheimer's disease and use those signatures to develop a predictive model. We examined the expression patterns of m6A regulators and immune features in Alzheimer’s disease using the GSE33000 dataset. We examined the immune cell infiltration and molecular groups based on m6A-related genes in 310 Alzheimer's disease samples. The WGCNA algorithm was utilized to determine differently expressed genes within each cluster. After evaluating the strengths and weaknesses of the random forest model, the support vector machine model, the generalized linear model, and eXtreme Gradient Boosting, the best machine model was selected. Methods such as nomograms, calibration curves, judgment curve analysis, and the use of independent data sets were used to verify the accuracy of the predictions made. Alzheimer's disease and non-disease Alzheimer's groups were compared to identify dysregulated m6A-related genes and activated immune responses. In Alzheimer's disease, two molecular clusters linked to m6A were identified. Immune infiltration analysis indicated substantial variation in protection between groups. Cluster 1 included processes like the Toll-like receptor signaling cascade, positive regulation of chromatin binding, and numerous malignancies; cluster 2 included processes like the cell cycle, mRNA transport, and ubiquitin-mediated proteolysis. With a lower residual and root mean square error and a larger area under the curve (AUC = 0.951), the Random forest machine model showed the greatest discriminative performance. The resulting random forest model was based on five genes, and it performed well (AUC = 0.894) on external validation datasets. Accuracy in predicting Alzheimer's disease subgroups was also shown by analyses of nomograms, calibration curves, and decision curves. In this research, we methodically outlined the tangled web of connections between m6A and AD and created a promising prediction model for gauging the correlation between m6A subtype risk and AD pathology.

Climate change has triggered a series of global problems, posing a huge threat to the distribution of many plants and animals, especially endangered species such as the giant panda. Therefore, predicting the distribution of habitat quality under climate change conditions is of great significance for protecting these species. In this study, we examined the correlation between suitable habitat index and ecosystem services using 260 occurrence records and 13 environmental factors with giant pandas as the model species. The species distribution models can also be employed to predict and compare the potential geographical distribution of giant pandas at present and in the 2050s and 2090s in the Qinling Mountains of Shaanxi Province. The results show the following: (1) The relationship between suitable habitat index and ecosystem services of giant panda is not uniform. (2) From 2040 to 2100, the existing habitats may decrease by 47.8% to 98.5%. (3) The main direction of change in the center of the distribution of the giant panda’s habitat is to migrate first eastward and then northwestward. Our results regarding the potential distribution pattern of giant pandas in the Qinling Mountains and their response to climate change can provide important references for optimizing the conservation and habitat management of wild giant pandas in the Qinling Mountains.

Abstract Background The positioning of implant components for total hip arthroplasty (THA) is essential for joint stability, polyethylene liner wear, and range of motion. One potential benefit of the direct anterior approach (DAA) for THA is the ability to use intraoperative fluoroscopy for acetabular cup positioning and limb-length evaluation. Previous studies comparing intraoperative fluoroscopy with no fluoroscopy during DAA have reported conflicting results. This meta-analysis aimed to evaluate whether intraoperative fluoroscopy improves component positioning compared to no fluoroscopy during direct anterior total hip arthroplasty. Methods A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted. We searched Web of Science, EMBASE, PubMed, Cochrane Controlled Trials Register, Cochrane Library, Highwire, CBM, CNKI, VIP, and Wanfang database in May 2023 to identify studies involving intraoperative fluoroscopy versus no fluoroscopy during direct anterior total hip arthroplasty. Finally, we identified 1262 hips assessed in seven studies. Results There were no significant differences in terms of acetabular cup inclination angle (ACIA, P = 0.21), ACIA within safe zone rate (P = 0.97), acetabular cup anteversion angle (ACAA, P = 0.26); ACAA within safe zone rate (P = 0.07), combined safe zone rate (P = 0.33), and limb-length discrepancy (LLD, P = 0.21) between two groups. Conclusion Even though intraoperative fluoroscopy was not related to an improvement in cup location or LDD. With fewer experienced surgeons, the benefit of intraoperative fluoroscopy might become more evident. More adequately powered and well-designed long-term follow-up studies were required to determine whether the application of the intraoperative fluoroscopy for direct anterior total hip arthroplasty will have clinical benefits and improve the survival of prostheses.

Abstract Objective: The relationships between childhood weight self-misperception and obesity-related factors particularly health markers have not been extensively discussed. This study aims to examine the associations between weight self-misperception and obesity-related knowledge, attitudes, lifestyles and cardio-metabolic markers among Chinese paediatric population. Design: Cross-sectional study. Setting: Data sourced from a national survey in Chinese seven provinces in 2013. Participants: Children and adolescents aged 5–19 years. Results: Of the total 14 079 participants, there were 14·5 % and 2·2 % participants over-estimated and under-perceived their weight, respectively. Multi-variable logistic regression was applied to calculate OR and 95 % CI (95 % Cl) of obesity-related behaviours and cardio-metabolic markers by actual and perceived weight status. Individuals who perceived themselves as overweight/obese were more likely to have prolonged screen time, insufficient dairy intake and over sugar-sweetened beverages consumption (all P < 0·05), regardless of their weight. Furthermore, actual overweight/obese individuals had higher odds of abnormal cardio-metabolic markers, but a smaller magnitude of association was found among weight under-estimators. Among non-overweight/obese individuals, weight over-estimation was positively associated with abdominal obesity (OR: 10·49, 95 % CI: 7·45, 14·76), elevated blood pressure (OR: 1·30, 95 % CI: 1·12, 1·51) and dyslipidemia (OR: 1·43, 95 % CI: 1·29, 1·58). Conclusions: Weight over-perception was more prevalent than under-estimation, particularly in girls. Weight over-estimators tended to master better knowledge but behave more unhealthily; both weight over-perception and actual overweight/obesity status were associated with poorer cardio-metabolic markers. Future obesity intervention programmes should additionally pay attention to the population with inaccurate estimation of weight who were easily overlooked.

Abstract The scale-free ferroelectric polarization of fluorite MO2 (M = Hf, Zr) due to flat polar phonon bands are promising for nonvolatile memories. Defects are also widely introduced to improve the emergent ferroelectricity. However, their roles are still not fully understood at the atomic-level. Here, we report a significant effect of point-defect-driven flattening of polar phonon bands with more polar modes and polarization contribution in doped MO2. The polar phonon bands in La-doped MO2 (M = Hf, Zr) can be significantly flattened, compared with pure ones. However, the lower energy barrier with larger polarization of V O -only doped MO2 compared with La-doped cases suggest that V O and local lattice distortion should be balanced for high-performance fluorite ferroelectricity. The work is believed to bridge the relation between point defects and the generally enhanced induced ferroelectricity in fluorite ferroelectrics at the atomic-level and inspire their further property optimization via defect-engineering.

Abstract Background Neoadjuvant chemotherapy followed by radical cystectomy (RC) is the standard of care for patients with muscle‐invasive bladder cancer (MIBC). However, treatment outcomes are suboptimal. Camrelizumab, a PD‐1 blockade, has shown benefits in several tumors. This study aimed to investigate the efficacy and safety of neoadjuvant camrelizumab in combination with gemcitabine plus cisplatin (GC) followed by RC for MIBC patients. Methods This was a multi‐center, single‐arm study that enrolled MIBC patients with a clinical stage of T2‐4aN0‐1M0, and scheduled for RC. Patients received three 21‐day cycles of camrelizumab 200 mg on day 1, gemcitabine 1000 mg/m2 on day 1 and 8, and cisplatin 70 mg/m2 on day 2, followed by RC. The primary endpoint was pathologic complete response (pCR, pT0N0). Results From May 2020 to July 2021, 43 patients were enrolled and received study medications at nine centers in China. Three of them were deemed ineligible and excluded from efficacy analysis but included in safety analysis. In total 10 patients were unevaluable as they declined RC (two due to adverse events [AEs] and eight due to patient's willingness). Among 30 evaluable patients, 13 patients (43.3%) achieved pCR, and 16 patients (53.3%) achieved pathologic downstaging. No AEs leading to death were observed. The most common AEs were anemia (69.8%), decreased white blood cell count (65.1%), and nausea (65.1%). Immune‐related AEs were all grade 1 or 2. Pathologic response was not correlated with PD‐L1 expression status or tumor mutation burden. Individual genes as a biomarker for pathologic response were not identified. Conclusions Neoadjuvant treatment with camrelizumab and GC regimen demonstrated preliminary anti‐tumor activity for MIBC patients with manageable safety profiles. The study met its primary endpoint, and the following randomized trial is ongoing.

Abstract Background Infectious diseases pose a significant risk to the health and well-being of children and adolescents, and can even be life-threatening. Thus, our study aimed to explore the effectiveness of health education based on the social-ecological model in improving the knowledge of infectious diseases among this vulnerable population. Methods This study was a school-based intervention conducted in seven Chinese provinces in 2013, involving a total of 26,591 children and adolescents in the intervention group and 24,327 in the control group. The intervention group received a comprehensive health intervention based on the social-ecological model (SEM) over six months, which included a supportive environment, health education on infectious diseases, guidance on self-monitoring infectious disease-related behaviors, and other measures. Data on infectious disease-related knowledge and other characteristics were collected through questionnaires. The main outcome measure will be the difference in the effectiveness of health education regarding infectious diseases in children and adolescents between baseline and post-intervention. A mixed-effects regression model was used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) to assess the impact of infectious disease-related interventions on the participants. Results We utilized a socioecological model as the foundation for a six-month health education program on infectious diseases targeting children and adolescents in the intervention group. At the individual and community levels, the correct rate of health behavior related to infectious diseases in the intervention group was higher than that in the control group (P

Abstract Background Shift work, with its growing prevalence globally, disrupts the body's inherent circadian rhythm. This disruption may escalate the risk of chronic diseasesxacerbate chronic disease risk by dysregulating physiological, behavioral, and psychosocial pathways. This study aimed to evaluate the effect of shift work on type 2 diabetes (T2DM) and Retinol binding protein 4 (RBP4) level. Methods The current study employed a multi-stage stratified cluster sampling technique, examining 1499 oilfield workers from the OHSPIW cohort who participated in occupational health assessments between March 2017 and June 2018.The evaluation involved shift work, sleep quality, T2DM status with questionnaires and plasma RBP4 levels in blood samples. Statistical analysis includes, Chi-square tests, t-tests, multivariate logistic regression analyses, and multivariate linear mixed models. Results The prevalence rate of T2DM in shift workers (6.56%) was significantly higher than in day workers (4.21%) (OR = 1.60, 95% CI: 1.01–2.53), with no significant difference found in the family history of diabetes, hypertension, or other chronic heart diseases (P = 0.378). The shift worker (6.89 ± 3.35) also exhibited distinctly higher PSQI scores than day workers (5.99 ± 2.87) (P

Plants lack behavioral responses to avoid dramatic environmental changes associated with the annual seasons. For survival, they have evolved complex sensory systems to sense fluctuations in light and optimize their architecture in response to changes in these cues. Phytochrome A (phyA) was initially identified as a photoreceptor that senses far-red light signals. It was then identified as playing a central role in promoting hypocotyl growth, fiber development, and flowering time in a variety of plants including Arabidopsis, rice, soybean and cotton. Under dark conditions, phyA is present in the cytoplasm in the physiologically inactive (Pr) form. Far-red light signals induce the transformation of Pr into the physiologically active (Pfr) form, after which Pfr-phyA is recognized by FAR-RED ELONGATED HYPOCOTYL 1 (FHY1) and FHY1-LIKE (FHL) and translocated to the nucleus, initiating a series of signaling cascades. The current review comprehensively summarizes recent advances in understanding the function of phyA in plants, including phyA-mediated shade avoidance and flowering time. Remaining issues and possible directions for future research on phyA are also discussed.

Abstract Natural articular cartilage is a typical self‐healing and superlubrication system capable of maintaining extremely low friction under physiological loadings. Cartilage wear and accidental trauma can cause irreversible defects to cartilage and subchondral bone with a significant decrease in intra‐articular lubrication, leading to the development of severe osteoarthritis and osteochondral defect. To address the important clinical problem of osteochondral defect, a bioinspired hard–soft (PEEK‐lubrication hydrogel) composite scaffold is designed and developed. The polymerization of polyethylene glycol diacrylamide (PEGDAA) and 2‐methacryloyloxyethyl phosphorylcholine (MPC) on polyetheretherketone (PEEK) substrate is achieved by UV initiation to form a strong interfacial bonding, and nano‐hydroxyapatite is deposited on porous PEEK substrate via polydopamine coating to improve osteogenic capability. Accordingly, the composite scaffold is successfully developed with lubrication and osteogenic activity. The tribological tests show that the lubrication performance of the composite scaffold is based on the hydration lubrication mechanism of the upper hydrogel layer, and the in vitro and in vivo experiments demonstrate that the composite scaffold is endowed with excellent biocompatibility and bioactivity. In conclusion, the bioinspired strategy for preparing a hard–soft composite scaffold shows a promising way in the treatment of osteochondral defect and provided a guideline for designing functional PEEK‐based biomaterials in tissue engineering scaffolds.

The Nidirana Dubois, 1992 exhibit a ubiquitous presence in East and Southeast Asia, spanning from Japan west to southern China and from northern Thailand to northern Vietnam and Laos in the south. The taxonomic categorisations pertaining to this genus continue to be a subject of debate, particularly with regard to those species that possess broad geographical distributions. In China, 18 species of Nidirana are currently recognised.We describe a new species of this genus from south-western China. Mitochondrial 16S and COⅠ gene phylogenetic analyses support the new species as an independent clade nested within the Nidirana. The new species is phylogenetically close to N. yaoica, with a genetic distance of 2.5% from its sister taxon. Morphologically, the new species can be distinguished from congeners by a combination of the following characteristics: males relatively small (SVL 41.8-43.3 mm); lateroventral grooves present on both fingers and toes; relative finger length Ⅱ < Ⅰ < Ⅳ < Ⅲ; tibio-tarsal articulation reaching to the level of the eye or nostril; a pair of external subgular vocal sacs in males; one single nuptial pad on the dorsal surface of the base of the first finger in males during the breeding season; webbing formula I 1/2 - 1 II 1/2 - 2 III 1 - 2½ IV 2 - 1V.

Chronic cadmium (Cd) exposure causes severe adverse health effects on the human body, especially the kidney tissue. Studies have demonstrated oxidative stress to be involved in renal pathological variations after exposure to Cd, but few effective treatments are available for the disease yet. Therefore, the present study was carried out to investigate the potential therapeutic intervention and its underlying molecular mechanisms of melatonin (MT), a natural antioxidant with multiple biological activities, against renal injury caused by Cd exposure in mice. C57BL/6 male mice (eight-week-old) were intragastrically administered with CdCl2, MT, or both for 30 days. Biochemical analysis showed that MT intervention significantly improved the SOD, GSH, and CAT activities while markedly decreasing the kidney MDA content of the mice exposed to Cd. Histological examination indicated that Cd exposure resulted in the atrophy of the renal glomerular, the degeneration and dilation of tubules, and the accumulation of fibrocytes. By contrast, MT administration effectively ameliorated the histological outcome of the injured kidney tissue. Moreover, administrating MT significantly inhibited proinflammatory cytokines TNF-α and iNOS expression in Cd-treated mice. Further, MT treatment markedly suppressed the expressions of renal fibrosis-related factors TGF-β1, α-SMA, and collagen Ⅰ in the injured renal tissue and the accumulation and development of renal fibrosis. In addition, the administration of MT significantly reduced the expression of caspase-3 and cell apoptotic death in the kidney tissue of Cd-exposed mice. In all, the data showed that MT has a compelling therapeutic potential in alleviating the pathological variations of renal injury caused by Cd exposure.

Background: Sepsis is a complex, life-threatening clinical syndrome that can cause other related diseases, such as acute kidney injury (AKI). Circular RNA (circRNA) is a type of non-coding RNA with a diverse range of functions, and it plays essential roles in miRNA sponge. CircRNA plays a huge part in the development of various diseases. CircRNA and the competing endogenous RNA (ceRNA) regulatory network are unknown factors in the onset and progression of septic AKI (SAKI). This study aimed to clarify the complex circRNA-associated regulatory mechanism of circRNAs in SAKI.Methods: We collected 40 samples of whole blood of adults, including 20 cases of SAKI and 20 cases of healthy controls. Moreover, five cases were each analyzed by RNA sequencing, and we identified differentially expressed circRNA, miRNA, and mRNA (DEcircRNAs, DEmiRNAs, and DEmRNAs, respectively). All samples were from SAKI patients with intraperitoneal infection.Results: As a result, we screened out 236 DEcircRNAs, 105 DEmiRNAs, and 4065 DEmRNAs. Then, we constructed two co-expression networks based on RNA–RNA interaction, including circRNA–miRNA and miRNA–mRNA co-expression networks. We finally created a circRNA–miRNA–mRNA regulation network by combining the two co-expression networks. Functional and pathway analyses indicated that DEmRNAs in ceRNA were mostly concentrated in T cell activation, neutrophils and their responses, and cytokines. The protein–protein interaction network was established to screen out the key genes participating in the regulatory network of SAKI. The hub genes identified as the top 10 nodes included the following: ZNF727, MDFIC, IFITM2, FOXD4L6, CIITA, KCNE1B, BAGE2, PPIAL4A, USP17L7, and PRSS2.Conclusion: To our knowledge, this research is the first study to describe changes in the expression profiles of circRNAs, miRNAs, and mRNAs in patients with SAKI. These findings provide a new treatment target for SAKI treatment and novel ideas for its pathogenesis.

Background: Early onset of puberty could have significant impacts on childhood health, but the extent to which it was affected by phthalate esters (PAEs) and sex hormone disruption was not understood. The aim of this study is to investigate the associations between exposure to PAEs and sex hormone disruption and early onset of puberty in children. Methods: A longitudinal cohort study was conducted in China from May 2017 to Oct 2020, involving 740 children during consecutive visits. The onset of puberty was evaluated using Tanner definition, and early puberty was defined as an onset age less than the first 25 %, with cut-offs of 10.33 and 8.97 years for boys and girls, respectively. Serum testosterone (TT), estradiol (E2) and urinary PAE metabolites were measured during three visits. Generalized linear models were used to explore the associations between PAE and sex hormones with the age of puberty onset, while log-binomial regressions were applied to assess the associations of persistent exposure to PAEs and sex hormones with early pubertal onset. Results: Approximately 86.0 % of boys and 90.2 % of girls completed puberty onset from pre-puberty, and more than 95 % of participants had PAE concentrations higher than the limit of detection. Boys showed higher exposure to PAE pollutants and higher TT levels. Persistent exposure to PAEs was positively associated with early pubertal onset in girls (ARR = 1.97, 95 %CI = 1.12, 3.46). Moreover, persistent exposure to PAEs and E2 had synergistic associations with early pubertal onset in both boys (ARR = 4.77, 95 %CI = 1.06, 21.54) and girls (ARR = 7.07, 95 %CI = 1.51, 33.10). However, PAEs and TT had antagonistic associations only in boys (ARR = 0.44, 95 %CI = 0.07, 2.58). Conclusion: Long-term exposure to PAEs might increase the risk of early pubertal onset, and it appears to work in synergy with E2, while in antagonism with TT in boys’ early pubertal onset. Reducing PAEs exposure might promote pubertal health.

Abstract Ultrasonic fluid bubble detection is important in industrial controls, aerospace systems and clinical medicine because it can prevent fatal mechanical failures and threats to life. However, current ultrasonic technologies for bubble detection are based on conventional bulk PZT-based transducers, which suffer from large size, high power consumption and poor integration with ICs and thus are unable to implement real-time and long-term monitoring in tight physical spaces, such as in extracorporeal membrane oxygenation (ECMO) systems and dialysis machines or hydraulic systems in aircraft. This work highlights the prospect of capacitive micromachined ultrasonic transducers (CMUTs) in the aforementioned application situations based on the mechanism of received voltage variation caused by bubble-induced acoustic energy attenuation. The corresponding theories are established and well validated using finite element simulations. The fluid bubbles inside a pipe with a diameter as small as 8 mm are successfully measured using our fabricated CMUT chips with a resonant frequency of 1.1 MHz. The received voltage variation increases significantly with increasing bubble radii in the range of 0.5–2.5 mm. Further studies show that other factors, such as bubble positions, flow velocities, fluid medium types, pipe thicknesses and diameters, have negligible effects on fluid bubble measurement, demonstrating the feasibility and robustness of the CMUT-based ultrasonic bubble detection technique.

Abstract To investigate the prevalence and indoor environmental influencing factors of wheeze and asthma among preschool children in Urumqi, Xinjiang, China to provide a strong basis for prevention and control. In August 2019, a cross-sectional study involving 8153 preschool children was conducted in 60 kindergartens in Urumqi. The ALLHOME-2 questionnaire was used for childhood wheeze and asthma survey, and the dampness in buildings and health (DBH) questionnaire was used for the childhood home dwelling and living environment survey. Multivariate unconditional logistic regression was then used to analyze the potential influencing factors of childhood asthma and wheeze. The prevalence of wheeze and asthma in children was 4.7% and 2.0%, respectively. Multivariate unconditional logistic regression results suggested that ethnicity other than the Han Chinese (odds ratio (OR) 1.39, 95% confidence interval (CI) 1.05–1.84), caesarean section (OR 1.24, 95% CI 1.00–1.53), family history of asthma (OR 5.00, 95% CI 3.36–7.44), carpet or floor bedding at home (OR 1.40, 95% CI 1.05–1.87), purchasing new furniture in the mother’s residence during pregnancy (OR 1.58, 95% CI 1.06–2.36), pet keeping in the residence at aged 0–1 year (OR 1.55, 95% CI 1.13–2.13), passive smoking by child in the current residence (OR 1.35, 95% CI 1.01–1.80), and having mould or hygroma in the child's residence at aged 0–1 year (OR 1.72, 95% CI 1.12–2.64) were risk factors for wheeze. In addition, Girls (OR 0.73, 95% CI 0.59–0.90) was a protective factor for wheeze. Caesarean section (OR 1.46, 95% CI 1.06–2.00), family history of asthma (OR 7.06, 95% CI 4.33–11.53), carpet or floor bedding at home (OR 2.20, 95% CI 1.50–3.23), and pet keeping in the residence at aged 0–1 year (OR 1.64, 95% CI 1.04–1.83) were risk factors for asthma, whereas Girls (OR 0.58, 95% CI 0.42–0.80) was a protective factor for asthma. This survey indicates that the purchase of new furniture, the placement of carpet or floor bedding in the child's residence, the pets keeping, room dampness or moldy phenomena, and passive smoking may all contribute to an elevated risk of wheeze or asthma in children.

With the continuous development of infrared technology, the application of infrared imagery is increasingly widespread. Nonetheless, infrared imagery suffers from low contrast and high noise characteristics, making it challenging to detect and recognize infrared small targets. Frequently, existing deep learning-based infrared target detection methods solely employ spatial information, neglecting frequency domain information, thereby creating susceptibility to background clutter interference and low detection accuracy in complex scenes. Here, a deep learning-based method is proposed that combines frequency domain clutter suppression and spatial feature extraction to detect infrared small targets. Firstly, the spatial domain infrared image is transformed into the frequency domain using block discrete cosine transform (DCT). Secondly, the frequency domain information is filtered using an attention mechanism to adaptively enhance the targets and suppress the background clutter. Finally, the compressed attention map is transformed back to the spatial domain and inputted into a lightweight neural network for spatial feature extraction and fusion to obtain detection results. This approach enhances detection accuracy, and reduces computational complexity and storage space, thereby making it practical and deployable. Experimental outcomes demonstrate strong detection capabilities on public datasets, and significant advantages over traditional and existing deep learning methods.

Abstract Background Morphological markers presenting the lateral extension of acromion and the greater tuberosity of humerus were proposed to diagnose and predict rotator cuff tears (RCTs) in recent years, but few studies have addressed the combined performance when using two predictors together. As a presence of a RCT may be associated with the impingement caused by both acromion and the greater tuberosity, we believe a combined utilization of predictors could result in a better diagnostic and predictive performance than using a single predictor. The aim of this study is to (i) explore whether the combination is more efficient to predict and diagnose RCTs; (ii) find out which combination is the most superior screening approach for RCTs. Methods This was a retrospective study and patients who visited our hospital and were diagnosed with or without partial-thickness or full-thickness RCTs via magnetic resonance imaging from January 2018 to April 2022 were enrolled and classified into two groups respectively. Four predictors, the critical shoulder angle (CSA), the acromion index (AI), the greater tuberosity angle (GTA) and the double-circle radius ratio (DRR) were picked to participate in the present study. Quantitative variables were compared by independent samples t tests and qualitative variables were compared by chi-square tests. Binary logistic regression analysis was used to construct discriminating combined models to further diagnose and predict RCTs. Receiver operating characteristic (ROC) curves were pictured to determine the overall diagnostic performance of the involved predictors and the combined models. Results One hundred and thirty-nine shoulders with RCTs and 57 shoulders without RCTs were included. The mean values of CSA (35.36 ± 4.57 versus 31.41 ± 4.09°, P

Major depressive disorder (MDD) with diabetes mellitus (DM) significantly reduces the quality of the patient's life, and currently, there is no effective treatment. This study explored the feasibility of Glucagon-like peptide-1 (GLP-1) in treating MDD combined with DM. The protective effects of GLP-1 on mouse hippocampal neuronal cell line HT22 cultured with corticosterone (CORT) and high glucose (HG) were assessed. HT22 cells were cultured with CORT + HG to construct a cell model of MDD combined with DM. Cell viability and cell apoptosis/necrocytosis were detected by CCK-8 assay and flow cytometry/confocal laser scanning microscopy, respectively, after treatment with GLP-1. In addition, BDNF and neurotransmitter levels, lactic dehydrogenase (LDH) and glucose levels, and proteins of cAMP-CREB-BDNF signal pathway in the culture supernatants were measured through an enzyme-linked immunosorbent assay and colorimetric assays and Western blot, respectively. The ideal intervention combination to construct a cell model of MDD combined with DM was CORT 200 μM and HG 50 mM for 48 h. After treatment of 50 nM GLP-1 for 48 h, the model+50 nM GLP-1 group's apoptosis and necrocytosis rates and LDH and glucose concentrations in the culture supernatants decreased significantly compared with the model group. However, the BDNF, 5-hydroxytryptamine (5-HT), dopamine (DA), norepinephrine (NE), PKA, p-CREB, and p-Trkb concentrations in the culture supernatants increased significantly. GLP-1 functioned against CORT + HG-induced toxicity by activating the cAMP-CREB-BDNF signaling pathway in hippocampal neuronal cells.

The Wushan Salamander (Liua shihi), Jinfo Salamander (Pseudohynobius jinfo), and Wenxian Knobby Salamander (Tylototriton wenxianensis) are rare national Class II protected wild animals in China. We performed MaxEnt modeling to predict and analyze the potential distribution and trends of these species in Chongqing under current and future climate conditions. Species distribution data were primarily obtained from field surveys, supplemented by museum collections and the existing literature. These efforts yielded 636 records, including 43 for P. jinfo, 23 for T. wenxianensis, and 570 for L. shihi. Duplicate records within the same 100 m × 100 m grid cell were removed using ENMTools, resulting in 10, 12, and 58 valid distribution points for P. jinfo, T. wenxianensis, and L. shihi, respectively. The optimization of feature class parameters (FC) and the regularization multiplier (RM) were applied using R package “ENMeval 2.0” to establish the optimal model with MaxEnt. The refined models were applied to simulate the suitable distribution areas for the three species. The results indicate that the current suitable habitat area for L. shihi accounted for 9.72% of the whole region of the Chongqing municipality. It is projected that, by 2050, the proportion of suitable habitat will increase to 12.54% but will decrease to 11.98% by 2070 and further decline to 8.80% by 2090. The current suitable habitat area for P. jinfo accounted for 1.08% of the whole region of the Chongqing municipality, which is expected to decrease to 0.31%% by 2050, 0.20% by 2070, and 0.07% by 2090. The current suitable habitat area for T. wenxianensis accounted for 0.81% of the whole region of the Chongqing municipality, which is anticipated to decrease to 0.37% by 2050, 0.21% by 2070, and 0.06% by 2090. Human disturbance, climate variables, and habitat characteristics are the primary factors influencing the distribution of three salamander species in Chongqing. The proximity to roads significantly impacts L. shihi, while climate conditions mainly affect P. jinfo, and the distance to water sources is crucial for T. wenxianensis. The following suggestions were made based on key variables identified for each species: (1) For L. shihi, it is imperative to minimize human disturbances and preserve areas without roads and the existing vegetation within nature reserves to ensure their continued existence. (2) For P. jinfo, the conservation of high-altitude habitats is of utmost importance, along with the reduction in disturbances caused by roads to maintain the species’ ecological niche. (3) For T. wenxianensis, the protection of aquatic habitats is crucial. Additionally, efforts to mitigate the impacts of road construction and enhance public awareness are essential for the preservation of this species and the connectivity of its habitats.

The precise control of free auxin (indole-3-acetic acid, IAA) gradient, which is orchestrated by biosynthesis, conjugation, degradation, hydrolyzation, and transport, is critical for all aspects of plant growth and development. Of these, the GRETCHEN HAGEN 3 (GH3) acyl acid amido synthetase family, pivotal in conjugating IAA with amino acids, has garnered significant interest. Recent advances in understanding GH3-dependent IAA conjugation have positioned GH3 functional elucidation as a hot topic of research. This review aims to consolidate and discuss recent findings on (i) the enzymatic mechanisms driving GH3 activity, (ii) the influence of chemical inhibitor on GH3 function, and (iii) the transcriptional regulation of GH3 and its impact on plant development and stress response. Additionally, we explore the distinct biological functions attributed to IAA-amino acid conjugates.

Some H5 viruses isolated in poultry or wild birds between 2020 and 2021 were found to be antigenically different from the vaccine strains (H5-Re11 and H5-Re12) used in China. In this study, we generated three new recombinant vaccine seed viruses by using reverse genetics and used them for vaccine production. The vaccine strain H5-Re13 contains the hemagglutinin (HA) and neuraminidase (NA) genes of an H5N6 virus that bears the clade 2.3.4.4h HA gene, H5-Re14 contains the HA and NA genes of an H5N8 virus that bears the clade 2.3.4.4b HA gene, and H7-Re4 contains the HA and NA genes of H7N9 virus detected in 2021. We evaluated the protective efficacy of the novel H5/H7 trivalent inactivated vaccine in chickens, ducks, and geese. The inactivated vaccine was immunogenic and induced substantial antibody responses in the birds tested. Three weeks after vaccination, chickens were challenged with five different viruses detected in 2020 and 2021: three viruses (an H5N1 virus, an H5N6 virus, and an H5N8 virus) bearing the clade 2.3.4.4b HA gene, an H5N6 virus bearing the clade 2.3.4.4h HA gene, and an H7N9 virus. All of the control birds shed high titers of virus and died within 4 days post-challenge, whereas the vaccinated chickens were completely protected from these viruses. Similar protective efficacy against H5 viruses bearing the clade 2.3.4.4h or 2.3.4.4b HA gene was observed in ducks and geese. Our study indicates that the newly updated H5/H7 vaccine can provide solid protection against the H5 and H7N9 viruses that are currently circulating in nature.

IntroductionWe aimed to investigate the association between greenness around schools, long-term gaseous air pollution exposure (SO2 and CO), and blood pressure in children and adolescents.MethodsFrom 2006 to 2018, a total of 219,956 Chinese children and adolescents aged 7–17 years in Beijing and Zhongshan were included in this longitudinal study. Annual average concentrations of SO2 and CO and the mean values of normalized difference vegetation index around schools were calculated. We used the generalized estimation equation model, restricted cubic spline model, and Cox model to analyze the health effects.ResultsAmong all the subjects, 52,515 had the first onset of HBP. During the follow-up, HBP's cumulative incidence and incidence density were 23.88% and 7.72 per 100 person-year respectively. Exposures to SO2 and CO were significantly associated with SBP [β = 1.30, 95% CI: (1.26, 1.34) and 0.78 (0.75, 0.81)], DBP [β = 0.81 (0.79, 0.84) and 0.46 (0.44, 0.48)] and HBP [HR = 1.58 (1.57, 1.60) and 1.42 (1.41, 1.43)]. The risks of HBP attributed to SO2 and CO pollution would be higher in school-aged children in the low greenness group: the attributable fractions (AFs) were 26.31% and 20.04%, but only 13.90% and 17.81% in the higher greenness group. The AFs were also higher for normal-BMI children and adolescents in the low greenness group (AFs = 30.90% and 22.64%, but 14.41% and 18.65% in the high greenness group), while the AFs were not as high as expected for obese children in the low greenness group (AFs = 10.64% and 8.61%), nor was it significantly lower in the high greenness group (AFs = 9.60% and 10.72%).DiscussionGreenness could alleviate the damage effects of SO2/CO exposure on the risks of HBP among children and adolescents, and the benefit is BMI sensitivity. It might offer insights for policymakers in making effective official interventions to prevent and control the prevalence of childhood HBP and the future disease burden caused by air pollution.

Background:Macleaya cordata extract (MCE) is effective in the treatment of enteritis, but its mechanism has not been fully elucidated. Therefore, this study combined network pharmacology and molecular docking technologies to investigate the potential pharmacological mechanism of MCE in the treatment of enteritis.Methods: The information of active compounds in MCE was accessed through the literature. Furthermore, PubChem, PharmMapper, UniProt, and GeneCards databases were used to analyze the targets of MCE and enteritis. The intersection of drug and disease targets was imported into the STRING database, and the analysis results were imported into Cytoscape 3.7.1 software to construct a protein–protein interaction (PPI) network and to screen core targets. The Metascape database was used for conducting Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. AutoDock Tools software was used for the molecular docking of active compounds with the core targets.Results: MCE has four active compounds, namely, sanguinarine, chelerythrine, protopine, and allocryptopine, and a total of 269 targets after de-duplication. Furthermore, a total of 1,237 targets were associated with enteritis, 70 of which were obtained by aiding the drug–disease intersection with the aforementioned four active compound targets of MCE. Five core targets including mitogen-activated protein kinase 1 (MAPK1) and AKT serine/threonine kinase 1 (AKT1) were obtained using the PPI network, which are considered the potential targets for the four active compounds of MCE in the treatment of enteritis. The GO enrichment analysis involved 749 biological processes, 47 cellular components, and 64 molecular functions. The KEGG pathway enrichment analysis revealed 142 pathways involved in the treatment of enteritis by the four active compounds of MCE, among which PI3K-Akt and MAPK signaling pathways were the most important pathways. The results of molecular docking showed that the four active compounds demonstrated good binding properties at the five core targets.Conclusion: The pharmacological effects of the four active compounds of MCE in the treatment of enteritis involve acting on signaling pathways such as PI3K-Akt and MAPK through key targets such as AKT1 and MAPK1, thus providing new indications for further research to verify its mechanisms.

The tunable band gap of PbS colloidal quantum dots (CQDs) from ultraviolet (UV) to short-wave infrared (SWIR) bands provides many potential applications in optoelectronics. However, synthesis of large-sized CQDs that exhibit good stability and sensitivity for extended wavelength still remains a technological challenge. In this paper, a novel broadband photodetector based on small size PbS CQDs (with exciton absorption peak at 927 nm) and Bi2Te3 (with wide spectral sensitivity and high absorption) was developed and studied. The device, which comprised of ITO/AZO/PbS CQDs/Bi2Te3/Al, provided an excellent band alignment that facilitated charge dissociation and transmission hence improving the device sensitivity. Furthermore, wavelength extension was also realized through the synergistic effect of these materials, thus demonstrating broadband photodetection with high sensitivity. The heterostructure photodetector demonstrated good performance in the visible and near infrared ranges, especially at a wavelength of 1050 nm exhibiting a high responsivity (R) and detectivity (D*) of 161 A/W and 3.2 × 1013 Jones, respectively. In addition, the device exhibited excellent stability and reversibility after one month of storage without any encapsulation. This work lays a good foundation for the construction of the next generation of highly sensitive broadband CQDs photodetectors.

BackgroundLeft subclavian artery (LSA) revascularization during thoracic endovascular aortic repair (TEVAR) is necessary to reduce postoperative complications in patients with Stanford type B aortic dissection and an insufficient proximal anchoring area. However, the efficacy and safety of different LSA revascularization strategies remain unclear. Here, we compared these strategies to provide a clinical basis for selecting an appropriate LSA revascularization method.MethodsIn this study, we included 105 patients with type B aortic dissection who were treated using TEVAR combined with LSA reconstruction in the Second Hospital of Lanzhou University from March 2013 to 2020. They were divided into four groups according to the method used for LSA reconstruction, namely, carotid subclavian bypass (CSB; n = 41), chimney graft (CG; n = 29), single-branched stent graft (SBSG; n = 21), and physician-made fenestration (PMF; n = 14) groups. Finally, we collected and analyzed the baseline, perioperative, operative, postoperative, and follow-up data of the patients.ResultsThe treatment success rate was 100% in all the groups, and CSB + TEVAR was the most commonly used procedure in emergency settings compared with the other three procedures (P 0.05) The median follow-up time of CSB, CG, SBSG, and PMF groups was significantly different (P

Objective In this study we concerned on the morphological characteristics of the greater tuberosity of humerus and proposed the double‐circle radius ratio as a new predictor for the diagnosis of rotator cuff tears. Methods This was a retrospective study and patients who visited our hospital and were diagnosed with or without rotator cuff tears via magnetic resonance imaging from January 2018 to July 2021 were enrolled and classified into two groups respectively. In a standard anteroposterior view, the radius of the best‐fit circle of humeral head and the radius of the concentric circle passing through the most lateral edge of the greater tuberosity were measured in each shoulder. The ratio of these two radiuses was named as the double‐circle radius ratio. Angular parameters including the greater tuberosity angle and the critical shoulder angle were also measured in the anteroposterior view. Independent samples t tests and chi‐square tests were used to find significant differences between groups. Significant associations between those measured variables and demographic characteristics were analyzed with simple linear regression analysis. Receiver operating characteristic curves were pictured to determine applied cutoff values by using Youden index. Multivariable‐adjusted analysis for the occurrence of rotator cuff tears was carried out by using multiple logistic regression analysis. For all tests a p value of 1.38 resulted in 11.252‐fold odds of developing rotator cuff tears (95% CI, 3.388–37.368; P = 0.000). Conclusion The double‐circle radius ratio is significantly larger in patients with rotator cuff tears and could be regarded as an eligible predictor for rotator cuff tears.

Abstract Background To evaluate the diagnostic performance of multiparametric transrectal ultrasound (TRUS) and to design diagnostic scoring systems based on four modes of TRUS to predict peripheral zone prostate cancer (PCa) and clinically significant prostate cancer (csPCa). Methods A development cohort involved 124 nodules from 116 patients, and a validation cohort involved 72 nodules from 67 patients. Predictors for PCa and csPCa were extracted to construct PCa and csPCa models based on regression analysis of the development cohort. An external validation was performed to assess the performance of models using area under the curve (AUC). Then, PCa and csPCa diagnostic scoring systems were established to predict PCa and csPCa. The diagnostic accuracy was compared between PCa and csPCa scores and PI-RADS V2, using receiver operating characteristics (ROC) and decision curve analysis (DCA). Results Regression models were established as follows: PCa = − 8.284 + 4.674 × Margin + 1.707 × Adler grade + 3.072 × Enhancement patterns + 2.544 × SR; csPCa = − 7.201 + 2.680 × Margin + 2.583 × Enhancement patterns + 2.194 × SR. The PCa score ranged from 0 to 6 points, and the csPCa score ranged from 0 to 3 points. A PCa score of 5 or higher and a csPCa score of 3 had the greatest diagnostic performance. In the validation cohort, the AUC for the PCa score and PI-RADS V2 in diagnosing PCa were 0.879 (95% confidence interval [CI] 0.790–0.967) and 0.873 (95%CI 0.778–0.969). For the diagnosis of csPCa, the AUC for the csPCa score and PI-RADS V2 were 0.806 (95%CI 0.700–0.912) and 0.829 (95%CI 0.727–0.931). Conclusions The multiparametric TRUS diagnostic scoring systems permitted better identifications of peripheral zone PCa and csPCa, and their performances were comparable to that of PI-RADS V2.

Abstract Background Segmental testicular infarction is a rare condition that often occurs in the upper pole of the left testicle and usually presents with acute onset of scrotal pain. Contrast-enhanced ultrasound and MR are essential for diagnosing and differentiating segmental testicular infarction in clinical practice, and conservative treatment can only be adopted after a definitive diagnosis. In the present case, after conservative treatment, the infarct volume was reduced, the blood flow around the infarct was increased, and blood flow signals appeared in the infarct. We performed a correlation analysis to investigate the causes of these changes. Case presentation A 33-year-old male, without any specific disease history, was admitted to the hospital with a 5-day history of left testicular pain, and the imaging showed focal necrosis of the left testicle with hemorrhage. He was diagnosed with segmental testicular infarction after differentiating and excluding it from malignant tumors. Conservative medical treatment was given, and the symptoms of testicular pain were relieved after treatment. After discharge, regular reexamination at follow-ups showed that the infarct’s size was reduced, the blood flow around the infarct was increased, and blood flow signals appeared in the infarct. Conclusion Conservative treatment has become the standard treatment currently adopted after confirming the diagnosis of segmental testicular infarction through contrast-enhanced ultrasound and MR. The blood flow changes in and around the focus of testicular infarction can be related to various factors. At present, relevant conclusions of the underlying mechanisms were mainly deduced from infarction studies of other related organs such as the heart and brain; thus, the specific pathological mechanism needs further experimental verification.

Abstract Background Despite Vast improvements in technology and surgical technique in total knee arthroplasty (TKA), approximately 15–25% TKAs, have suboptimal subjective clinical outcomes. Our study sought to evaluate if sensor-guided balancing improves postoperative clinical outcomes compared to a conventional gap balancing technique. Methods We searched Web of Science, Embase, PubMed, Cochrane Controlled Trials Register, Cochrane Library, Highwire, CBM, CNKI, VIP, and Wanfang database in March 2022 to identify studies involving sensor-guided balancing versus conventional gap balancing technique in TKA. Finally, we identified 2147 knees assessed in nine studies. Results Compared with manual gap balancing, Sensor-guided gap balancing resulted in less rate of Manipulation under anesthesia (MUA) (P = 0.02), however more rate of intraoperative additional procedures (P = 0.0003). There were no significant differences in terms of KSS (P = 0.21), KSS Function score (P = 0.36), OKS (P = 0.61), KOOS (P = 0.78), operative time (P = 0.17), Mechanical axis (P = 0.69) and rate of reoperation between two groups. Conclusion Compared with conventional manual gap balancing techniques, sensors have more balancing procedures being performed. However, it did result in a reduction in the rate of MUA. More extensive, high-quality RCTs are required to verify our findings further.

Abstract Introduction The efficacy of tourniquet use during primary total knee arthroplasty (TKA) is thought to reduce intraoperative blood loss, improve surgical exposure, and optimize cement fixation. Tranexamic acid (TXA) use can decrease postsurgical blood loss and transfusion requirements. This review aimed to appraise the effects of tourniquet use in TKA for patients with tranexamic acid use. Methods A meta-analysis was conducted to identify relevant randomized controlled trials involving TXA plus a tourniquet (TXA-T group) and use of TXA plus no tourniquet (TXA-NT group) in TKA. Web of Science, PubMed, Embase, Cochrane Controlled Trials Register, Cochrane Library, Highwire, CNKI, and Wanfang database were searched from 2010 through October 2021. Results We identified 1720 TKAs (1690 patients) assessed in 14 randomized controlled trials. Compared with the TXA-NT group, the TXA-T group resulted in less intra-operative blood loss (P