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Two cases of cutaneous angiosarcoma of the scalp and face in the elderly are reported. Case 1 was an 89 years old man with ulcerated edematous, erythematous plagues on the scalp and right face for 2 months. Dermatological examination showed that ulcerated edematous, erythematous patches on the crown, forehead, and right face, with unclear boundaries. The involved skin was tight, shiny, and depressed under pressure. Ulcers and scabs were present on the crown (sized 2 cm×3 cm) and frontotemporal region (sized 4 cm×6 cm). Histopathology showed necrosis and atypical cells arranged in luminal pattern around lesion in the dermis. Immunohistochemistry showed CD31 (+), CD34 (+), ERG (+), HHV8 focal weak positive, P53 mutation, Ki-67 (30% +), CK (-), and CEA (-). Diagnosis: angiosarcoma. The patient and his family refused further diagnosis and treatment, and the patient passed away. Case 2 was an 81 years old female with dark erythema on the right scalp and face for 2 months. Dermatological examination revealed purple patch covered with purple papules and nodules on the right scalp and face. Skin histopathology showed slight thickening of the spinous layers, diffuse proliferation of endothelial cells in the dermis, segmentation of collagen, and atypia. Fissures and vascular lumens containing erythrocytes were also observed in the dermis. Immunohistochemistry: CD31 (+), CD34 (+), D240(+), ERG(+), Ki-67(≈35%+), S100(-), HMB45(-), and CK(-). Diagnosis: angiosarcoma of the scalp and face. The patient was transferred to the oncology department for radiotherapy and chemotherapy, and passed away during follow-up.

Objective: This study aimed to investigate the factors influencing nurses’ ability to respond to public health emergencies and understand the relationship between nurses’ ability to respond to emergencies and workplace resilience. Methods: A cross-sectional study of 361 nurses from military hospitals was conducted from January 18 to September 6, 2022, using an online survey. The Infectious Diseases Emergency Response Capacity (IDERC) questionnaire and the Workplace Resilience Scale (WRS) were utilized, and sociodemographic information was also collected. Data were analyzed using descriptive statistics and frequency analysis. Differences between groups were identified by one-way analysis of variance, and linear regression was used to analyze the main factors influencing the infectious emergency response capacity. Results: The average infectious emergency response capacity score on the IDERC questionnaire and workplace resilience, measured by WRS, were 4.01 (SD = 0.76) and 3.85 (SD = 0.71), respectively, on a scale of 1–5, indicating high performance. Factors such as degree of education, nurses’ service years and experience in epidemic prevention participation were found to be the main influencing factors of the score of IDERC. The level of workplace resilience showed a positive correlation with the capacity to respond to infectious disease, the score of WRS and the service year accounted for 63.6% of the variance in emergency response capabilities. Conclusion: The results indicate an urgent need to strengthen the training of nurses with lower degree of education, shorter service years, no prior work, or no experience of epidemic prevention participation, and hospitals should also prioritize improving nurses’ workplace resilience through targeted interventions, enhancing their abilities in infectious disease prevention, preparation, first aid, and subsequent critical patient care.

Abstract Background The objective was to investigate the efficacy of different doses of levothyroxine therapy among pregnant women exhibiting high-normal thyroid stimulating hormone levels and positive thyroid peroxidase antibodies throughout the first half of pregnancy. Methods Pregnant women exhibiting high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positivity throughout the initial half of pregnancy were selected from January 2021 to September 2023. Based on the different doses of levothyroxine, the pregnant women were categorized into the nonintervention group (G0, 122 women), 25 µg levothyroxine intervention group (G25, 69 women), and 50 µg levothyroxine intervention group (G50, 58 women). Serum parameters, gastrointestinal symptoms, small intestinal bacterial overgrowth (SIBO), maternal and neonatal outcomes were compared after the intervention among the three groups. Results After the intervention, in the G25 and G50 groups, the thyroid stimulating hormone, triglyceride and low-density lipoprotein levels were notably less in contrast to those in the G0 group (P

Abstract DANCE is the first standard, generic, and extensible benchmark platform for accessing and evaluating computational methods across the spectrum of benchmark datasets for numerous single-cell analysis tasks. Currently, DANCE supports 3 modules and 8 popular tasks with 32 state-of-art methods on 21 benchmark datasets. People can easily reproduce the results of supported algorithms across major benchmark datasets via minimal efforts, such as using only one command line. In addition, DANCE provides an ecosystem of deep learning architectures and tools for researchers to facilitate their own model development. DANCE is an open-source Python package that welcomes all kinds of contributions.

Bartonella spp. are globally distributed gram-negative facultative intracellular bacteria that infect a wide range of hosts. Rodents are natural reservoirs of many Bartonella species, some of which are also pathogenic to humans. The rapid development of transportation and tourism has highlighted the risk of Bartonella transmission to humans. Thus, it is essential to maintain surveillance of Bartonella spp. infections in rodents. In China, Bartonella spp. infections have been monitored in various areas; however, these have not included the Hulunbuir border regions. In the present study, we monitored the prevalence and genetics of rodent-associated Bartonella spp. in the Hulunbuir border regions. Eleven rodent species were captured at five ports. Eight species were confirmed as Bartonella-positive using quantitative PCR assay, with an overall positivity rate of 20.05 %. Lasiopodomys brandtii was the predominant rodent species captured for Bartonella detection. Sequencing and phylogenetic analysis (using the maximum likelihood method) revealed the presence of three Bartonella species in these rodents, including two pathogenic to humans, namely, Bartonella alsatica and Bartonella grahamii. B. grahamii was the predominant Bartonella species identified in the rodents. Taken together, these results highlight the prevalence and genetic diversity of Bartonella spp. in rodents in the Hulunbuir border regions, indicating the need for risk assessment of human spillover.

GeSn materials with Sn contents ranging between 0% and 11% have been successfully grown by using Ge2H6 and SnCl4 in a hot-wall UHV-CVD system at low reaction pressures of 0.2–0.4 Torr. Both fully strained and partially relaxed materials have been produced. It was found that the materials were of high crystallinity as evidenced by few threading dislocations from cross-sectional TEM. Photoluminescence studies have shown that the PL spectra shift to longer wavelengths, and the PL intensity increases exponentially as the Sn contents increase. The photoemission cutoff for a 9.5% Sn sample is beyond 2600 nm, and low temperature PL measurements have confirmed that this sample is already in the direct gap material regime. Prototype photoconductor devices were fabricated with a partially strained 5% Sn sample, showing much smaller dark currents and similar spectral coverage as compared to a fully strained 7.8% Sn device reported in the literature. The reported technical route has provided a new path toward high quality, low cost GeSn epitaxy, and will contribute to the development of group IV optoelectronics.

Calcium sulfate, generally in the form of gypsum or bassanite, is a significant component in oil well cement. The impact of gypsum/bassanite on the fluid loss of cement slurry was thoroughly examined with varied concentrations of a 2-Acrylamido-2-methylpropane sulfonic acid based fluid loss additive (AMPS-FLA). It was found that bassanite in cement was more conducive to decreasing the fluid loss than gypsum. The results showed that the dissolution rate of bassanite in cement slurry was faster than that of gypsum, generating more Ca2+ and resulting in a reduction in the adsorption capacity of the AMPS-FLA on cement particle surfaces. The adsorption mechanism of FLAs cannot explain the result. This study discovered that the equilibrium concentration of the AMPS-FLA in the pore solution had a good functional relationship with the fluid loss, which was not impacted by cement components. Increasing the equilibrium concentration helped reduce the fluid loss.

ABSTRACT: Avian leukemia virus subgroup J (ALV-J) and chicken infectious anemia virus (CIAV) can be vertically transmitted; however, the pathogenicity of vertically transmitted coinfection with these 2 pathogens has not been studied. In this study, we created a model of chick morbidity in which chicks carried either ALV-J, CIAV, or both viruses via embryo inoculation. Thereafter, we analyzed the effects of vertically transmitted coinfection with CIAV and ALV-J on the pathogenicity of ALV-J and performed a purification assay based on hatching, mortality viremia positivity, and detection of fecal ALV-p27 antigen rates, and body weight. The hatching rate of the ALV-J+CIAV group was 68.57%, lower than those of the single infection and control groups. The survival curve showed that the mortality rates of the CIAV and ALV-J coinfection groups were higher than those of the single infection and control groups. Body weight statistics showed that coinfection aggravated the 7-d growth inhibition effect. The results of ALV-p27 antigen detection in cell culture supernatants showed that the positivity rates of the ALV-J and ALV-J+CIAV groups were 100% at all ages and 0% in the control group. The results of ALV-p27 antigen detection by anal swabs showed that the positivity rates of the ALV-J group were 92.86, 90.90, 88.89, and 93.33% at all ages, and that the ALV-J p27 positivity detection rate of anal swabs was lower than that of plasma virus isolation. The immune organ index of the ALV-J+CIAV group was significantly or very significantly lower than those of the single infection and control groups. The immune organ viral load showed that coinfection with CIAV and ALV-J promoted the proliferation of ALV-J and CIAV in immune organs. Coinfection with ALV-J and CIAV reduced chicken embryo hatchability and increased chick mortality and growth inhibition relative to their respective single infections. Additionally, coinfection with ALV-J + CIAV was even more detrimental in inducing immune organ atrophy (e.g., the thymus, spleen, and bursa), and promoted individual virus replication during coinfection.

ABSTRACT: Marek's disease virus (MDV) is a significant tumorigenic virus that causes severe immunosuppression in chickens. Lentinan (LNT) is an immunomodulator containing β-glucans and is widely used in areas such as antiviral, anticancer, and immune regulation. To investigate the immunomodulatory effects of LNT on specific pathogen-free (SPF) chicks and its potential to inhibit MDV infection, we conducted an MDV challenge experiment and observed the immune-enhancing effect of LNT on SPF chicks. The results showed that LNT promoted the growth and development of SPF chicks and induced the upregulation of cytokines such as Mx protein, interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α), and interleukin-2 (IL-2). The specific gravity of CD4+ T-lymphocytes and CD8+ T-lymphocytes and their ratios were also significantly upregulated. Prophylactic use of LNT inhibited MDV replication in lymphocytes, liver, and spleen. It also alleviated MDV-induced weight loss and hepatosplenomegaly in SPF chicks. The present study confirms that LNT can enhance the levels of innate and cellular immunity in SPF chicks and contributes to the inhibition of MDV replication in vivo and mitigation of immune organ damage in chicks due to MDV infection. This provides an adjunctive measure for better control of MDV infection.

The rotation of targets in high-resolution synthetic aperture radar (SAR) images results in complex and nonlinear micro-Doppler modulation of SAR returns, exhibiting distinct and diverse imaging characteristics under different conditions. This poses challenges to image interpretation, target detection and recognition. This article establishes signal models for single and multiple scattering of rotating targets in high-resolution spaceborne SAR and, in conjunction with the processing procedures of range Doppler algorithm (RDA), derives the azimuth bandwidth and the conditions for azimuth frequency aliasing caused by rotation. Quantitative analysis of the errors introduced by target rotation in various signal domains is performed, taking into account the stationary phase point offset, the rotation-induced range migration correction error, and the change of azimuth phase in detail. In addition, representative signatures of these influences in SAR images are simulated and interpreted and more accurate theoretical models of imaging results are derived. The processing and analysis of both simulation and real measured data validate the correctness of the theoretical derivation in this study and provide support for the interpretation and information extraction of high-resolution SAR rotating targets.

Abstract Background Thoracoscopic surgical techniques continue to advance, yet the intensity of postoperative pain remains significant, impeding swift patient recovery. This study aimed to evaluate the differences in postoperative pain and recuperation between patients receiving intrathecal morphine paired with low-dose bupivacaine and those administered general anesthesia exclusively. Methods This randomized controlled trial enrolled 100 patients, who were allocated into three groups: Group M (5 μg/kg morphine intrathecal injection), Group B (5 μg/kg morphine combined with bupivacaine 3 mg intrathecal injection) and Group C (intrathecal sham injection). The primary outcome was the assessment of pain relief using the Numeric Rating Scale (NRS). Additionally, intraoperative remifentanil consumption was quantified at the end of the surgery, and postoperative opioid use was determined by the number of patient-controlled analgesia (PCIA) compressions at 48 h post-surgery. Both the efficacy of the treatments and any complications were meticulously recorded. Results Postoperative NRS scores for both rest and exercise at 6, 12, 24, and 48 h were significantly lower in groups M and B than in group C (P0.05). There was no significant difference in intraoperative propofol dosage across all three groups (P>0.05). Postoperative dosages of both sufentanil and Nonsteroidal anti‐inflammatory drugs (NSAIDs) were significantly less in groups M and B compared to group C (P

Abstract Yes-associated protein (YAP) is a pivotal regulator in cellular proliferation, survival, differentiation, and migration, with significant roles in embryonic development, tissue repair, and tumorigenesis. At the maternal–fetal interface, emerging evidence underscores the importance of precisely regulated YAP activity in ensuring successful pregnancy initiation and progression. However, despite the established association between YAP dysregulation and adverse pregnancy outcomes, insights into the impact of aberrant YAP levels in fetal-derived, particularly trophoblast cells, and the ensuing dysfunction at the maternal–fetal interface remain limited. This review comprehensively examines YAP expression and its regulatory mechanisms in trophoblast cells throughout pregnancy. We emphasize its integral role in placental development and maternal–fetal interactions and delve into the correlations between YAP dysregulation and pregnancy complications. A nuanced understanding of YAP's functions during pregnancy could illuminate intricate molecular mechanisms and pave the way for innovative prevention and treatment strategies for pregnancy complications. Video Abstract

Background Although several studies have addressed plasma proteomics in heart failure with preserved ejection fraction, limited data are available on the prognostic value of urinary proteomics. The objective of our study was to identify urinary proteins/peptides associated with death and heart failure admission in patients with heart failure with preserved ejection fraction. Methods and Results The study population included participants enrolled in TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial). The relationship between urine protein levels and the risk of death or heart failure admission was assessed using Cox regression, in both nonadjusted analyses and adjusting for urine creatinine levels, and the MAGGIC (Meta‐Analysis Global Group in Chronic Heart Failure) score. A total of 426 (12.4%) TOPCAT participants had urinary protein data and were included. There were 40 urinary proteins/peptides significantly associated with death or heart failure admission in nonadjusted analyses, 21 of which were also significant adjusted analyses. Top proteins in the adjusted analysis included ANGPTL2 (angiopoietin‐like protein 2) (hazard ratio [HR], 0.5731 [95% CI, 0.47–0.7]; P=3.13E‐05), AMY2A (α amylase 2A) (HR, 0.5496 [95% CI, 0.44–0.69]; P=0.0001), and DNASE1 (deoxyribonuclease‐1) (HR, 0.5704 [95% CI, 0.46–0.71]; P=0.0002). Higher urinary levels of proteins involved in fibrosis (collagen VI α‐1, collagen XV α‐1), metabolism (pancreatic α‐amylase 2A/B, mannosidase α class 1A member 1), and inflammation (heat shock protein family D member 1, inducible T cell costimulatory ligand) were associated with a lower risk of death or heart failure admission. Conclusions Our study identifies several novel associations between urinary proteins/peptides and outcomes in heart failure with preserved ejection fraction. Many of these associations are independent of clinical risk scores and may aid in risk stratification in this patient population.

BackgroundHospital resilience is essential in responding to disasters, but current research focuses mainly on frameworks and models rather than the protection of resilience and analysis of risk factors during public health emergencies. This study aims to examine the development of resilience in Chinese frontline hospitals during the initial COVID-19 outbreak in 2020, providing insights for future disaster response efforts.ObjectivesWe conducted interviews with 26 hospital staff members who were involved in the initial response to the COVID-19 outbreak in China. We used a semi-structured interview approach and employed purposive sampling and snowball sampling techniques. The interview outline was guided by the ‘Action Framework’ proposed by the World Health Organization (WHO) for responding to infectious disease emergencies. This framework includes dimensions such as command, surveillance, risk communication, medical response, and public health response. We analyzed the collected data using Colaizzi’s seven-step data analysis method and the template analysis method.ResultsWHO’s ‘action framework’ effectively highlights the factors that contribute to hospital resilience. While medical response, including the availability of materials and facilities, the use of information technology, and the capacity for infectious disease diagnosis and treatment, remains crucial, other important aspects include awareness and beliefs about infections, treatment experience, interdisciplinary collaboration, and more. Additionally, it is essential to establish an intelligent command system, foster trusting partnerships between teams, improve monitoring capabilities for infectious disease agents, enhance risk communication through information synchronization and transparency, strengthen infection control planning, and improve environmental disinfection capabilities for effective public health emergency response. These contradictions significantly impact the enhancement of hospital resilience in dealing with major infectious disease outbreaks.ConclusionIn responding to sudden major infectious diseases, hospitals play a vital role within the healthcare system. Enhancing hospital resilience involves more than just improving treatment capabilities. It also requires effective command coordination at the hospital level, infection control planning, and the deployment of intelligent equipment. Additionally, planning for effective communication and coordination between hospitals, communities, and the national healthcare system can further enhance hospital resilience.

Abstract Asterias amurensis has attracted widespread concern because of its population outbreaks, which has impacted fisheries and aquaculture, as well as disrupting local ecosystems. A high-quality reference genome is necessary to better investigate mechanisms of outbreak and adaptive changes. Combining PacBio HiFi and Hi-C sequencing data, we generated a chromosome-level A. amurensis genome with a size of 491.53 Mb. The contig N50 and scaffold N50 were 8.05 and 23.75 Mb, respectively. The result of BUSCO analysis revealed a completeness score of 98.85%. A total of 16,531 protein-coding genes were predicted in the genome, of which 94.63% were functionally annotated. The high-quality genome assembly resulting from this study will provide a valuable genetic resource for future research on the mechanism of population outbreaks and invasion ecology.

Abstract Background Caveolin-1 (Cav-1) is a pivotal protein in the plasma membrane. Studies on homozygous Cav-1 deficient mice revealed that Cav-1 is essential for endothelial function and angiogenesis in the retina. However, whether a reduction in Cav-1 content hampers the neurovascular unit (NVU) in the retina is unclear. Thus, this study examines the NVU in the retinas of heterozygous Cav-1 deficient (Cav-1+/−) mice and analyzes possible underlying mechanisms. Methods The vascular, glial and neuronal components in the retina were evaluated using retinal morphometry, whole mount retinal immunofluorescence staining, histological analysis and optical coherence tomography. In addition, immunoblotting and immunofluorescence staining, subcellular fractionation, biotin labeling of cell surface proteins, and proximity ligation assay were employed to detect expression and localization of proteins in the retina or endothelial cells (ECs) upon knockdown of Cav-1 with Cav-1 siRNA. Results Cav-1+/− retinas showed a significant reduction in pericyte coverage along with an increase in acellular capillaries compared to controls at 8 months of age, but not at 1 month. A significant loss and obvious morphological abnormalities of smooth muscle cells were observed in 8-month-old Cav-1+/− retinal arterioles. Macroglial and microglial cells were activated in the Cav-1+/− retinas. A transient significant delay in retinal angiogenesis was detected in Cav-1+/− retinas at p5, which was however no longer detectable at p10. The Cav-1+/− retinas displayed increased vascular permeability and a notable reduction in VEGFR2 content at 8 months. In vitro, siRNA-mediated knockdown experiments in ECs revealed that the loss of Cav-1 in ECs resulted in decreased levels of VEGFR2, VE-Cadherin and their interaction at the plasma membrane as well. Conclusion Our results indicate that a sufficient Cav-1 level over 50% of its normal abundance is vital for the proper localization of VEGFR2 and VE-cadherin, likely in a complex, at the plasma membrane, which is essential for the maintenance of normal NVU in the retina.

Abstract Stretchable and curved electronic devices are a promising technology trend due to their remarkable advantages. Many approaches have been developed to manufacture stretchable and curved electronics. Here, to allow such electronics to better serve practical applications, ranging from wearable devices to soft robotics, we propose a novel vertical serpentine conductor (VSC) with superior electrical stability to interconnect functional devices through a silicon-based microfabrication process. Conformal vacuum transfer printing (CVTP) technology was developed to transfer the networked platform onto complex curved surfaces to demonstrate feasibility. The mechanical and electrical performance were investigated numerically and experimentally. The VSC interconnected network provides a new approach for stretchable and curved electronics with high stretchability and reliability.

【Objective】Avian leukosis virus subgroup J (ALV-J) and reticuloendotheliosis virus (REV) can be transmitted vertically through chicken embryos, and there have been reports of chicken embryos that are co-infected with the two viruses, however, the pathogenicity of co-infection between the two through chicken embryos has not been studied. An experimental animal model of vertical transmission of ALV-J and REV was established to study the pathogenicity of vertical transmission of ALV-J and REV and its effect on the purification test of avian leukaemia, with a view to providing a reference for the promotion of the synergistic purification of multiple pathogens.【Method】An infection model for chicks carrying ALV-J, REV and co-infected with the two viruses was constructed respectively by means of chicken embryo inoculation, and the pathogenicity of co-infection of REV and ALV-J in vertical transmission was analyzed by the indexes of hatching rate, mortality rate, body weight, fetal-feces ALV-p27 antigen detection rate, and viraemia positive rate.【Result】The hatching rate of the chicken embryos in the co-infection group of ALV-J+REV was 65.71%, which was lower than that in the mono-infection group and CK; the mortality rate in the co-infection group was higher than that in the mono-infection group and CK. The average weights of chicken in the CK, ALV-J group, REV group and ALV-J+REV group were 59.25, 50.83, 49.67, 43.78 g, indicating that co-infection increased the inhibition of growth. The results of ALV plasma virus isolation showed that the positive rates of ALV-J group and ALV-J+REV group were 100% at each day age, while the rate of CK was 0%. The results of anal swabs collected for the detection of ALV-27 antigen showed that the positive rates of ALV-J + REV group were 91.30%, 93.75%, 90.90% and 100% at day age (s) of 1, 3, 7 and 14, respectively, and the positive detection rate of ALV-J p27 in anal swabs was lower than that of plasma virus isolation. Comparison of the results of the immune organ development showed that, both ALV-J mono-infection and REV mono-infection could lead to the atrophy of chicken immune organs, while co-infection of them aggravated the degree of atrophy. The viral load of immune organs showed that the co-infection of REV and ALV-J promoted the proliferation of ALV-J in immune organs, while ALV-J also promoted the proliferation of REV in immune organs.【Conclusion】Co-infection of ALV-J and REV reduced embryo hatching rate, increased chick mortality and enhanced growth inhibition compared with mono-infection of ALV-J and REV, and the effect was more pronounced on inducing atrophy of immune organs such as the thymus, spleen and bursa, and both promoted mutual replication during co-infection.

Abstract The rapidly evolving landscape of biomarkers for colorectal cancer (CRC) necessitates an integrative, updated repository. In response, we constructed the Colorectal Cancer Biomarker Database (CBD), which collected and displayed the curated biomedicine information for 870 CRC biomarkers in the previous study. Building on CBD, we have now developed CBD2, which includes information on 1569 newly reported biomarkers derived from different biological sources (DNA, RNA, protein, and others) and clinical applications (diagnosis, treatment, and prognosis). CBD2 also incorporates information on nonbiomarkers that have been identified as unsuitable for use as biomarkers in CRC. A key new feature of CBD2 is its network analysis function, by which users can investigate the visible and topological network between biomarkers and identify their relevant pathways. CBD2 also allows users to query a series of chemicals, drug combinations, or multiple targets, to enable multidrug, multitarget, multipathway analyses, toward facilitating the design of polypharmacological treatments for CRC. CBD2 is freely available at http://www.eyeseeworld.com/cbd.

Breast cancer continues to have a high incidence rate among female malignancies. Despite significant advancements in treatment modalities, the heterogeneous nature of breast cancer and its resistance to various therapeutic approaches pose considerable challenges. Antibody-drug conjugates (ADCs) effectively merge the specificity of antibodies with the cytotoxicity of chemotherapeutic agents, offering a novel strategy for precision treatment of breast cancer. Notably, trastuzumab emtansine (T-DM1) has provided a new therapeutic option for HER2-positive breast cancer patients globally, especially those resistant to conventional treatments. The development of trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) has further broadened the applicability of ADCs in breast cancer therapy, presenting new hopes for patients with low HER2 expression and triple-negative breast cancer. However, the application of ADCs presents certain challenges. For instance, their treatment may lead to adverse reactions such as interstitial lung disease, thrombocytopenia, and diarrhea. Moreover, prolonged treatment could result in ADCs resistance, complicating the therapeutic process. Economically, the high costs of ADCs might hinder their accessibility in low-income regions. This article reviews the structure, mechanism of action, and clinical trials of commercially available ADCs for breast cancer treatment, with a focus on the clinical trials of the three drugs, aiming to provide insights for clinical applications and future research.

ABSTRACT The avian influenza virus (AIV), a member of the type A influenza virus group, is harbored by avian hosts. The highly pathogenic H5 subtype of AIV has inflicted significant financial damage on the poultry industry and also presents a possible pandemic hazard to the worldwide human population. There is an urgent need for a detection method that is both rapid and accurate in identifying H5-AIV. In this study, two assays based on reverse transcription recombinase-aided amplification technology (RT-RAA) have been developed to detect H5-AIV, namely, real-time fluorescence and reverse transcription recombinase-aided amplification (RF-RT-RAA) and reverse transcription recombinase-aided amplification combined lateral flow dipstick (RT-RAA-LFD). The completion of the two methods can be achieved in 30 min, and there was no cross-reaction with the nucleic acid of other avian pathogens. The results indicated that the lowest detectable limit of RF-RT-RAA and RT-RAA-LFD for H5-AIV detection was 1 copy/μL, which was 100 times higher than that of RT-PCR (102 copies/μL). A total of 376 samples, consisting of 350 clinical and 26 experimental samples, underwent testing utilizing virus isolation, RF-RT-RAA and RT-RAA-LFD methods, respectively. The results demonstrated a high degree of consistency between those assays. In summary, both the RF-RT-RAA and RT-RAA-LFD methods demonstrated excellent specificity and sensitivity, making them ideal for use in both laboratory and field settings. IMPORTANCE Avian influenza virus (AIV) subtype H5 is a highly contagious zoonotic disease and a serious threat to the farming industry and public health. Traditional detection methods, including virus isolation and real-time PCR, require tertiary biological laboratories and are time-consuming and complex to perform, making it difficult to rapidly diagnose H5 subtype avian influenza viruses. In this study, we successfully developed two methods, namely, RF-RT-RAA and RT-RAA-LFD, for rapid detection of H5-AIV. The assays are characterized by their high specificity, sensitivity, and user-friendliness. Moreover, the results of the reaction can be visually assessed, which are suitable for both laboratory testing and grassroots farm screening for H5-AIV.

Background: Smartphone addiction has emerged as a significant social problem. Numerous studies have indicated the association between smartphone use and discomfort in the musculoskeletal system of the upper extremities. Objects: This cross-sectional survey aimed to compare the characteristics of musculoskeletal pain in the neck, trunk, and upper limbs between individuals with smartphone addiction and those without addiction. Methods: We collected a total of 326 healthy individuals’ data from China and Korea who had owned and used smartphones for more than 5 years between 20–50s through an online questionnaire consisting of 84 questions in four major sections. The first part contained basic information on the participant's personal characteristics and smartphones. The second part contained questions about smartphone use and posture. The third part was the smartphone addiction. The fourth part was to investigate musculoskeletal pain in various upper body parts. Results: Smartphone addiction has a weak negative correlation with age (r = –0.20, p < 0.01) and a weak positive correlation with the hours of smartphone use (r = 0.376, p < 0.01). Frequent musculoskeletal pain symptoms related to smartphone use were observed in the neck, shoulder, lower back, and wrists. The hours of smartphone use was slightly positively associated with the prevalence of musculoskeletal pain in the shoulder (r = 0.162, p < 0.05) and lower back (r = 0.125, p < 0.05). The prevalence of musculoskeletal pain in the neck (χ2 = 3.993, p < 0.05), shoulder (χ2 = 6.465, p < 0.05), and wrist (χ2 = 4.645, p < 0.05) was significantly higher among females than males. Conclusion: The results suggest that smartphone addiction should be recognized as a dual concern encompassing both physical health and psychosocial aspects. Furthermore, healthcare professionals, including physicians and physical therapists, should consider clients' smartphone usage patterns when assessing and treating with musculoskeletal pain.

Abstract Background Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. Nonetheless, the accurate diagnosis of this condition continues to pose a challenge when relying on conventional diagnostic techniques. Cell death is a key factor in the pathogenesis of AF. Existing investigations suggest that cuproptosis may also contribute to AF. This investigation aimed to identify a novel diagnostic gene signature associated with cuproptosis for AF using ensemble learning methods and discover the connection between AF and cuproptosis. Results Two genes connected to cuproptosis, including solute carrier family 31 member 1 (SLC31A1) and lipoic acid synthetase (LIAS), were selected by integration of random forests and eXtreme Gradient Boosting algorithms. Subsequently, a diagnostic model was constructed that includes the two genes for AF using the Light Gradient Boosting Machine (LightGBM) algorithm with good performance (the area under the curve value > 0.75). The microRNA-transcription factor-messenger RNA network revealed that homeobox A9 (HOXA9) and Tet methylcytosine dioxygenase 1 (TET1) could target SLC31A1 and LIAS in AF. Functional enrichment analysis indicated that cuproptosis might be connected to immunocyte activities. Immunocyte infiltration analysis using the CIBERSORT algorithm suggested a greater level of neutrophils in the AF group. According to the outcomes of Spearman’s rank correlation analysis, there was a negative relation between SLC31A1 and resting dendritic cells and eosinophils. The study found a positive relationship between LIAS and eosinophils along with resting memory CD4+ T cells. Conversely, a negative correlation was detected between LIAS and CD8+ T cells and regulatory T cells. Conclusions This study successfully constructed a cuproptosis-related diagnostic model for AF based on the LightGBM algorithm and validated its diagnostic efficacy. Cuproptosis may be regulated by HOXA9 and TET1 in AF. Cuproptosis might interact with infiltrating immunocytes in AF.

Abstract This study presents a nitrogen-doped microporous carbon nanospheres (N@MCNs) prepared by a facile polymerization–carbonization process using low-cost styrene. The N element in situ introduces polystyrene (PS) nanospheres via emulsion polymerization of styrene with cyanuric chloride as crosslinking agent, and then carbonization obtains N@MCNs. The as-prepared carbon nanospheres possess the complete spherical structure and adjustable nitrogen amount by controlling the relative proportion of tetrachloromethane and cyanuric chloride. The friction performance of N@MCNs as lubricating oil additives was surveyed utilizing the friction experiment of ball-disc structure. The results showed that N@MCNs exhibit superb reduction performance of friction and wear. When the addition of N@MCNs was 0.06 wt%, the friction coefficient of PAO-10 decreased from 0.188 to 0.105, and the wear volume reduced by 94.4%. The width and depth of wear marks of N@MCNs decreased by 49.2% and 94.5%, respectively. The carrying capacity of load was rocketed from 100 to 400 N concurrently. Through the analysis of the lubrication mechanism, the result manifested that the prepared N@MCNs enter clearance of the friction pair, transform the sliding friction into the mixed friction of sliding and rolling, and repair the contact surface through the repair effect. Furthermore, the tribochemical reaction between nanoparticles and friction pairs forms a protective film containing nitride and metal oxides, which can avert direct contact with the matrix and improve the tribological properties. This experiment showed that nitrogen-doped polystyrene-based carbon nanospheres prepared by in-situ doping are the promising materials for wear resistance and reducing friction. This preparing method can be ulteriorly expanded to multi-element co-permeable materials. Nitrogen and boron co-doped carbon nanospheres (B,N@MCNs) were prepared by mixed carbonization of N-enriched PS and boric acid, and exhibited high load carrying capacity and good tribological properties.

In this study, liquid-liquid extraction-solvent assisted flavor evaporation (LLE-SAFE), headspace solid phase microextraction extraction (HS-SPME), gas chromatography-quadrupole-mass spectrometry (GC-Quadrupole-MS), gas chromatography-orbitrap-mass spectrometry (GC-Orbitrap-MS) and gas chromatography-olfactometry (GC-O) were used in combination to identify the volatile components in a fermented hawthorn wine (SBL-J) and a prepared hawthorn wine (FS), and the results of sensory analysis, modified frequency (MF) and odor activity value (OAV) were used to determine the key aroma compounds. Totally 89 aroma compounds were identified by LLE-SAFE/GC-O-MS. In addition, 29 and 38 aroma compounds with MF values of more than 20% were found in SBL-J and FS, respectively. A total of 123 volatile components were detected by HS-SPME/GC-Quadrupole-MS and HS-SPME/GC-Orbitrap-MS and there were 29 and 33 aroma compounds with OAV of greater than 1 (0.1 for esters) identified in SBL-J and FS, respectively. 2-Methybutyl acetate, ethyl hexanoate, ethyl octanoate and phenylethyl alcohol were the key aroma compounds in the two samples. To our knowledge, 2-methybutyl acetate, ethyl isovalerate, (E,E)-2,4-hexadienoic acid ethyl ester and ethyl butyrate, were identified for the first time as the key aroma components of hawthorn wine.

Fibrosis is one of the key factors that lead to the immune exclusion of solid tumors. Although degradation of fiber is a promising strategy, its application was still bottlenecked by the side effects of causing metastasis, resulting in the failure of immunotherapy. Here, we developed an antimetastatic polymer (HPA) for the delivery of chemo-drug and antifibrotic siPAI-1 to form the nano-permeator. Nano-permeator shrank after protonation and deeply penetrated into the tumor core to down-regulate the expression of PAI-1 for antifibrosis, and further promoted the sustained infiltration and activation of T cells for killing tumor cells. Moreover, metastasis after fiber elimination was prevented by multivalent CXCR4 antagonistic HPA to reduce the attraction of CXCL12 secreted by distant organs. The administration of stroma-alleviated immunotherapy increased the infiltration of CD8+ T cells to 52.5% in tumor tissues, inhibiting nearly 90% metastasis by HPA in distant organs. The nano-permeator reveals the mechanism and correlation between antifibrosis and antimetastasis and was believed to be the optimizing immunotherapy for solid fibrotic tumors.

ABSTRACTAlthough circular RNAs (circRNAs) play important roles in regulating gene expression, the understanding of circRNAs in livestock animals is scarce due to the significant challenge to characterize them from a biological sample. In this study, we assessed the outcomes of bovine circRNA identification using six enrichment approaches with the combination of ribosomal RNAs removal (Ribo); linear RNAs degradation (R); linear RNAs and RNAs with structured 3′ ends degradation (RTP); ribosomal RNAs coupled with linear RNAs elimination (Ribo-R); ribosomal RNA, linear RNAs and RNAs with poly (A) tailing elimination (Ribo-RP); and ribosomal RNA, linear RNAs and RNAs with structured 3′ ends elimination (Ribo-RTP), respectively. RNA-sequencing analysis revealed that different approaches led to varied ratio of uniquely mapped reads, false-positive rate of identifying circRNAs, and the number of circRNAs per million clean reads (Padj

An efficient obstacle detection system is one of the most important guarantees for improving the active safety performance of autonomous vehicles. This paper proposes an obstacle detection method based on high-precision positioning applied to blocked zones to solve the problems of the high complexity of detection results, low computational efficiency, and high load in traditional obstacle detection methods. Firstly, an NDT registration method which uses the likelihood function as the optimal value of the registration score function to calculate the registration parameters is designed to match the scanning point cloud and the target point cloud. Secondly, a target reduction method combined with threshold judgment and the binary tree search algorithm is designed to filter the point cloud of non-road obstacles to improve the processing speed of the computing platform. Meanwhile, KD-tree is used to speed up the clustering process. Finally, a vehicle remote control simulation platform with the combination of a cloud platform and mobile terminal is designed to verify the effectiveness of the strategy in practical application. The results prove that the proposed obstacle detection method can improve the efficiency and accuracy of detection.

This study systematically investigates the impact of pre-stretching amount (PSA) on the acceleration, motion status, and screening efficiency of the Flip-flow screen plate (FFSP). Initially, a nonlinear spring-multi-body model of the FFSP is established. Subsequently, the acceleration signals at the midpoint of the FFSP under various PSAs are measured and analyzed. The nonlinear stiffness coefficient of FFSP along the vertical direction is then determined and it is found that simplifying the nonlinear spring-multi-body system to a nonlinear spring-tri-body system under the experimental conditions can maintain the calculation error of FFSP’s acceleration within 30%. Phase and Poincaré mapping diagrams of the FFSP under different PSAs are subsequently created to illustrate the impact of PSA on the motion status of the FFSP. Finally, screening experiments are performed to study the optimal PSA for a kind of bituminous coal from Shanxi province.

Background: Stroke is one of the causes affecting gait and balance. Taping is considered an effective method for improving balance and gait in stroke patients. Numerous studies have confirmed the functional effects of taping in stroke patients. However, there is still no consensus regarding the use of taping to improve gait and balance. Objects: The purpose of this review was to investigate the effects of taping on the balance and gait of patients with stroke through meta-analysis of studies. Methods: PubMed, Medline, Embase, Web of Science, Cochrane Review, RISS, DBPia, and Science on were used to collect articles on Kinesio and non-elastic taping. The key terms were “Stroke”, “Hemiplegia”, “Taping”, “Tape”, “Balance”, and “Gait” with cut-off of October, 2022. Taping group was compared with control groups with sham, placebo, and no taping. The outcome measures included the Berg Balance Scale (BBS), Timed Up and Go (TUG) test, and gait speed (cm/s). Eighteen studies (524 patients) were selected for the meta-analysis. Results: Overall, taping improved balance and gait in stroke patients, and Kinesio and nonelastic taping had similar effect sizes. Taping improved the BBS and TUG, and was most effective on gait speed. Contrary to the expectation that a longer duration of taping would be more affective, taping was most effective when the total taping duration was shorter than 500 minutes. In addition, the effect size of taping was greater when it was simultaneously attached to multiple locations. Conclusion: This meta-analysis supports the use of taping to improve gait and balance in stroke patients, and provides guidelines for the location, duration, and type of tape to increase taping efficiency.

The motion of rotation is ubiquitous in daily life and industry. Compared with electromagnet motors, smart‐material‐based rotary motors may exhibit more flexibility, robustness, and adaptability. Herein, a lightweight, compact dielectric elastomer actuator (DEA) rotary motor with remarkable performance is reported. The motor is driven by a multilayered, slightly‐prestretched (

Avian influenza virus (AIV) causes huge losses to the global poultry industry and poses a threat to humans and other mammals. Fast, sensitive, and portable diagnostic methods are essential for efficient avian influenza control. Here, a clustered regularly interspaced short palindromic repeats (CRISPR)-Cas13a based platform was developed to detect AIV. This novel method was developed to specifically detect H1–H16 subtypes of AIV with fluorescence and lateral flow-based readouts and exhibited no cross-reactivity with Newcastle disease virus, avian infectious bronchitis virus, or infectious bursal disease virus. The limit of detection was determined to be 69 and 690 copies/μL using fluorescence and lateral flow as readouts, respectively. The developed assay exhibited 100% consistency with quantitative real-time polymerase chain reaction in detecting clinical samples. The heating of unextracted diagnostic samples to obliterate nuclease treatment was introduced to detect viral RNA without nucleic acid extraction. Single-step optimization was used to perform reverse transcription, recombinase polymerase amplification, and CRISPR-Cas13a detection in a tube. These advances resulted in an optimized assay that could specifically detect AIV with simplified procedures and reduced contamination risk, highlighting the potential to be used in point-of-care testing.

More than 700 million confirmed cases of Coronavirus Disease-2019 (COVID-19) have been reported globally, and 10–60% of patients are expected to exhibit “post-COVID-19 symptoms,” which will continue to affect human life and health. In the absence of safer, more specific drugs, current multiple immunotherapies have failed to achieve satisfactory efficacy. Ginseng, a traditional Chinese medicine, is often used as an immunomodulator and has been used in COVID-19 treatment as a tonic to increase blood oxygen saturation. Ginsenosides are the main active components of ginseng. In this review, we summarize the multiple ways in which ginsenosides affect post-COVID-19 symptoms, including inhibition of lipopolysaccharide, tumor necrosis factor signaling, modulation of chemokine receptors and inflammasome activation, induction of macrophage polarization, effects on Toll-like receptors, nuclear factor kappa-B, the mitogen-activated protein kinase pathway, lymphocytes, intestinal flora, and epigenetic regulation. Ginsenosides affect virus-mediated tissue damage, local or systemic inflammation, immune modulation, and other links, thus alleviating respiratory and pulmonary symptoms, reducing the cardiac burden, protecting the nervous system, and providing new ideas for the rehabilitation of patients with post-COVID-19 symptoms. Furthermore, we analyzed its role in strengthening body resistance to eliminate pathogenic factors from the perspective of ginseng-epidemic disease and highlighted the challenges in clinical applications. However, the benefit of ginsenosides in modulating organismal imbalance post-COVID-19 needs to be further evaluated to better validate the pharmacological mechanisms associated with their traditional efficacy and to determine their role in individualized therapy.

The genus Apiospora includes endophytes, pathogens and saprobes, with a wide host range and geographic distribution. In this paper, six Apiospora strains isolated from diseased and healthy tissues of bamboo leaves from Hainan and Shandong provinces in China were classified using a multi-locus phylogeny based on a combined dataset of ITS, LSU, tef1 and tub2, in conjunction with morphological characters, host association and ecological distribution. Two new species, Apiospora dongyingensis and A. hainanensis, and a new record of A. pseudosinensis in China, are described based on their distinct phylogenetic relationships and morphological analyses. Illustrations and descriptions of the three taxa are provided, along with comparisons with closely related taxa in the genus.

Abstract Inkjet printing technology is expected to enhance printed display mass production technology in the future. Nozzle-array printheads form the basis for printed display mass production applications. However, jet instability caused by air bubble entrapment and nozzle wettability changes during the printing process is a major challenge in the application of this technology. To adapt to possible nozzle abnormalities, a high-adaptability nozzle-array printing system based on a set covering printing planning (SCPP) model for printed display manufacturing is designed in this study. The study consists of two parts. First, a printing system based on multistep visual inspection and closed-loop feedback is proposed to accurately detect and screen abnormal nozzle positions. Notably, the inkjet printing system can identify nozzles with abnormal ejection characteristics and ensure that the remaining nozzles work accurately and stably. Then, an SCPP model is established for display pixel printing planning by using the remaining normal nozzles on the nozzle-array printhead. This model can output the most efficient printing path and nozzle printing action and can adapt to any pixel pattern, nozzle type, and abnormal nozzle distribution. The system and technology are highly adaptable and scalable for fabricating large-area printed display devices.

Objective: Taking gonad saponins from female of Apostichopus japonicus (AGS) as the research object to explore its immune-enhancing activity. Methods: The immunoregulatory activity of AGS in vitro was studied by measuring the phagocytosis and cytokines of macrophages. Thereafter the immunoregulatory activity of AGS in immunocompromised mice was analyzed by measuring thymus and spleen index, carbon clearance index and phagocytic index, proliferation activity of peritoneal macrophages, spleen cells, NK cell activity, T lymphocyte subsets level and serum cytokines of mice. Results: In vitro experiments showed that AGS could improve the phagocytic ability of macrophages and enhance the secretion of TNF-α, IL-6 and IFN-γ, and each group was significantly different from the normal group (P

Bovine viral diarrhoea virus (BVDV) is the etiologic agent of bovine viral diarrhea-mucosal disease, one of the most important viral diseases in cattle, with inflammatory diarrhea, enteritis, and mucosa necrosis as the major clinical manifestations. NF-κB is an important transcription complex that regulates the expression of genes involved in inflammation and immune responses. NLRP3 inflammasome plays a key role in the development of inflammatory diseases. However, whether the activation of NF-κB is crucial for BVDV infection-induced inflammatory responses remains unclear. The results of our present study showed that BVDV infection significantly activated the NF-κB pathway and promoted the expression of NLRP3 inflammasome components (NLRP3, ASC, pro-caspase 1) as well inflammatory cytokine pro-IL-1β in BVDV-infected bovine cells, resulting in the cleavage of pro-caspase 1 and pro-IL-1β into active form caspase 1 and IL-1β. However, the levels of the NLRP3 inflammasome components and inflammatory cytokines were obviously inhibited, as well the cleavage of pro-caspase 1 and pro-IL-1β in the pre-treated bovine cells with NF-κB-specific inhibitors after BVDV infection. Further, cytopathic biotype BVDV (cpBVDV) Erns and NS5A proteins with their key functional domains contributed to BVDV-induced inflammatory responses via activating the NF-κB pathway were confirmed experimentally. Especially, the NS5A can promote cholesterol synthesis and accelerate its augmentation, further activating the NF-κB signalling pathway. Conclusively, our data elucidate that the activation of NF-κB signaling pathway plays a crucial role in cpBVDV infection-induced inflammatory responses.

Feline viral diseases, such as feline panleukopenia, feline infectious peritonitis, and feline coronaviral enteritis, seriously endanger the health of cats, and restrict the development of pet industry. Meanwhile, there is a current lack of effective vaccines to protect against feline viral diseases. Thus, effective therapeutic agents are highly desirable. Interferons (IFNs) are important mediators of the antiviral host defense in animals, particularly type I IFNs. In this study, a novel feline IFN omega (feIFN-ω) gene was extracted from the cat stimulated with feline parvovirus (FPV) combined with poly(I:C), and following codon optimization encoding the feIFN-ω, the desired gene (feIFN-ω’) fragment was inserted into plasmid pPICZαA, and transformed into Pichia pastoris GS115, generating a recombinant P. pastoris GS115 strain expressing the feIFN-ω’. After induction, we found that the expression level of the feIFN-ω’ was two times more than that of feIFN-ω (p

Host circular RNAs (circRNAs) play critical roles in the pathogenesis of viral infections. However, how viruses modulate the biogenesis of host proviral circRNAs to facilitate their replication remains unclear. We have recently shown that Middle East respiratory syndrome coronavirus (MERS-CoV) infection increases co-expression of circRNAs and their cognate messenger RNAs (mRNAs), possibly by hijacking specific host RNA binding proteins (RBPs). In this study, we systemically analysed the interactions between the representative circRNA–mRNA pairs upregulated upon MERS-CoV infection and host RBPs. Our analysis identified heterogeneous nuclear ribonucleoprotein C (hnRNP C) as a key host factor that governed the expression of numerous MERS-CoV-perturbed circRNAs, including hsa_circ_0002846, hsa_circ_0002061, and hsa_circ_0004445. RNA immunoprecipitation assay showed that hnRNP C could bind physically to these circRNAs. Specific knockdown of hnRNP C by small interfering RNA significantly (P

Pepper (Capsicum annuum L.) is a herbaceous plant species in the family Solanaceae. Capsicum anthracnose is caused by the genus Colletotrichum. spp., which decreases pepper production by about 50% each year due to anthracnose. In this study, we evaluated the resistance of red ripe fruits from 17 pepper varieties against anthracnose fungus Colletotrichum capsici. We assessed the size of the lesion diameter and conducted significance analysis to identify the resistant variety of B158 and susceptible variety of B161. We selected a resistant cultivar B158 and a susceptible cultivar B161 of pepper and used a transcription to investigate the molecular mechanisms underlying the plant’s resistance to C. capsici, of which little is known. The inoculated fruit from these two varieties were used for the comparative transcription analysis, which revealed the anthracnose-induced differential transcription in the resistant and susceptible pepper samples. In the environment of an anthrax infection, we found that there were more differentially expressed genes in resistant varieties compared to susceptible varieties. Moreover, the response to stimulus and stress ability was stronger in the KANG. The transcription analysis revealed the activation of plant hormone signaling pathways, phenylpropanoid synthesis, and metabolic processes in the defense response of peppers against anthracnose. In addition, ARR-B, AP2-EREBP, bHLH, WRKY, and NAC are associated with disease resistance to anthracnose. Notably, WRKY and NAC were found to have a potentially positive regulatory role in the defense response against anthracnose. These findings contribute to a more comprehensive understanding of the resistance mechanisms of red pepper fruit to anthracnose infection, providing valuable molecular insights for further research on the resistance mechanisms and genetic regulations during this developmental stage of pepper.

The housing problem of young people is one of the manifestations of the imbalanced and insufficient development of China’s housing market. Solving housing issues for young people and improving their living conditions is of great significance for promoting the sustainable and healthy development of the real estate market. In order to analyze the housing issues of young people in China during the post-pandemic era, this paper investigates young people in the Nanjing Metropolitan Coordinating Region through questionnaires and interviews. The content of the questionnaire survey mainly includes the current housing situation, choice of renting or purchasing a home, expectations of real estate market, and future plans for purchasing a house of young people. The research results indicate that there are problems in the current housing market, such as strong purchasing preferences, imbalanced supply structure in the rental market, limited financial support for purchasing housing, low housing security levels, and small coverage of the housing provident fund. In order to solve the housing problems of young people, government departments should actively promote the formation of a multi-level housing supply structure, accelerate the promotion of the same rights for renting and purchasing, establish a standardized housing rental market, optimize the housing security policy for young people, and expand the coverage of the housing provident fund. The findings of this study have significant policy implications for easing the housing pressure on young people and building a youth-development-oriented city.

BackgroundAdolescents face unprecedented mental health challenges, and technology has the opportunity to facilitate access and support digitally connected generations. The combination of digital tools and live human connection may hold particular promise for resonating with and flexibly supporting young people’s mental health. ObjectiveThis study aimed to describe the BeMe app-based platform to support adolescents’ mental health and well-being and to examine app engagement, usability, and satisfaction. MethodsAdolescents in the United States, aged 13 to 20 years, were recruited via the web and enrolled between September 1 and October 31, 2022. App engagement, feature use, clinical functioning, and satisfaction with BeMe were examined for 30 days. BeMe provides content based on cognitive behavioral therapy, dialectical behavior therapy, motivational interviewing, and positive psychology; interactive activities; live text-based coaching; links to clinical services; and crisis support tools (digital and live). ResultsThe average age of the sample (N=13,421) was 15.04 (SD 1.7) years, and 56.72% (7612/13,421) identified with she/her pronouns. For the subsample that completed the in-app assessments, the mean scores indicated concern for depression (8-item Patient Health Questionnaire mean 15.68/20, SD 5.9; n=239), anxiety (7-item Generalized Anxiety Disorder Questionnaire mean 13.37/17, SD 5.0; n=791), and poor well-being (World Health Organization–Five Well-being Index mean 30.15/100, SD 16.1; n=1923). Overall, the adolescents engaged with BeMe for an average of 2.38 (SD 2.7) days in 7.94 (SD 24.1) sessions and completed 11.26 (SD 19.8) activities. Most adolescents engaged with BeMe’s content (12,270/13,421, 91.42%), mood ratings (13,094/13,421, 97.56%), and interactive skills (10,098/13,421, 75.24%), and almost one-fifth of the adolescents engaged with coaching (2539/13,421, 18.92%), clinical resources (2411/13,421, 17.96%), and crisis support resources (2499/13,421, 18.62%). Overall app engagement (total activities) was highest among female and gender-neutral adolescents compared with male adolescents (all P

Summary: Background: Racial/ethnic disparities in prostate cancer are reported in the United States (US). However, long-term trends and contributors of racial/ethnic disparities in all-cause and cause-specific death among patients with prostate cancer remain unclear. We analysed the trends and contributors of racial/ethnic disparities in prostate cancer survivors according to the cause of death in the US over 25 years. Methods: In this retrospective, population-based longitudinal cohort study, we identified patients diagnosed with first primary prostate cancer between 1995 and 2019, with follow-up until Dec 31, 2019, using population-based cancer registries’ data from the Surveillance, Epidemiology, and End Results (SEER) Program. We calculated the cumulative incidence of death for each racial/ethnic group (Black, white, Hispanic, Asian or Pacific Islander [API], and American Indian or Alaska Native [AI/AN] people), by diagnostic period and cause of death. We quantified absolute disparities using rate changes for the 5-year cumulative incidence of death between racial/ethnic groups and diagnostic periods. We estimated relative (Hazard ratios [HR]) racial/ethnic disparities and the percentage of potential factors contributed to racial/ethnic disparities using Cox regression models. Findings: Despite a decreasing trend in the cumulative risk of death across five racial/ethnic groups, AI/AN and Black patients consistently had the highest rate of death between 1995 and 2019 with an adjusted HR of 1.48 (1.40–1.58) and 1.40 (1.38–1.42) respectively. The disparities in all-cause mortality between AI/AN and white patients increased over time, with adjusted HR 1.32 (1.17–1.49) in 1995–1999 and 1.95 (1.53–2.49) in 2015–2019. Adjustment of stage at diagnosis, initial treatment, tumor grade, and household income explained 33% and 24% of the AI/AN-white and Black-white disparities in all-cause death among patients with prostate cancer. Interpretation: The enduring racial/ethnic disparities in patients with prostate cancer, call for new interventions to eliminate health disparities. Our study provides important evidence and ways to address racial/ethnic inequality. Funding: National Key R&D Program of China, National Natural Science Foundation of China, Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support, the Open Research Fund from Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Key Projects of Philosophy and Social Sciences Research, Ministry of Education of China.

Pepper (Capsicum annuum L) is one of the most important vegetables grown worldwide. Nevertheless, the key structural and regulatory genes involved in anthocyanin accumulation in pepper have not been well understood or fine mapped yet. In this study, F1, F2, BC1P1, and BC1P2 pepper populations were analyzed and these populations were derived from a cross between line 14-Z4, which has yellow anthers and green stems, and line 14-Z5, which has purple anthers and stems. The results showed that the yellow anthers and green stems were determined by a single recessive locus called to as ayw. While, using preliminary and fine mapping techniques, ayw locus was located between markers aywSNP120 and aywSNP124, with physical distance of 0.2 Mb. The CA11g18550 gene was identified as promising candidate for the ayw locus, as it co-segregated with the yellow anthers and green stems phenotypes. CA11g18550 encodes a homolog of the F3’5’H (flavonoid 3’,5’-hydroxylase) anthocyanin synthesis structure gene. The missense mutation of CA11g18550 possibly resulted in a loss-of-function. The expression analysis showed that CA11g18550 was significantly expressed in the stems, leaves, anthers and petals in 14-Z5, and it’s silencing caused the stems changing from purple to green. This study provides a theoretical basis for using yellow anthers and green stems in pepper breeding and helps to advance the understanding of anthocyanin synthesis.

Background: Diabetic retinopathy (DR) remains one of the most common complications of diabetes despite great efforts to uncover its underlying mechanisms. The pathogenesis of DR is characterized by the deterioration of the neurovascular unit (NVU), showing damage of vascular cells, activation of glial cells and dysfunction of neurons. Activation of the hexosamine biosynthesis pathway (HBP) and increased protein O-GlcNAcylation have been evident in the initiation of DR in patients and animal models. Scope of review: The impairment of the NVU, in particular, damage of vascular pericytes and endothelial cells arises in hyperglycemia-independent conditions as well. Surprisingly, despite the lack of hyperglycemia, the breakdown of the NVU is similar to the pathology in DR, showing activated HBP, altered O-GlcNAc and subsequent cellular and molecular dysregulation. Major conclusions: This review summarizes recent research evidence highlighting the significance of the HBP in the breakdown of the NVU in hyperglycemia-dependent and -independent manners, and thus identifies joint avenues leading to vascular damage as seen in DR and thus identifying novel potential targets in such retinal diseases.

Background: Virtual reality (VR) programs based on motion capture camera are the most convenient and cost-effective approaches for remote rehabilitation. Assessment of physical function is critical for providing optimal VR rehabilitation training; however, direct muscle strength measurement using camera-based kinematic data is impracticable. Therefore, it is necessary to develop a method to indirectly estimate the muscle strength of users from the value obtained using a motion capture camera.Objects: The purpose of this study was to determine whether the pedaling speed converted using the VR engine from the captured foot position data in the VR environment can be used as an indirect way to evaluate knee muscle strength, and to investigate the validity and reli-ability of a camera-based VR program.Methods: Thirty healthy adults were included in this study. Each subject performed a 15-sec-ond maximum pedaling test in the VR and built-in speedometer modes. In the VR speedom-eter mode, a motion capture camera was used to detect the position of the ankle joints and automatically calculate the pedaling speed. An isokinetic dynamometer was used to assess the isometric and isokinetic peak torques of knee flexion and extension.Results: The pedaling speeds in VR and built-in speedometer modes revealed a significant-ly high positive correlation (r = 0.922). In addition, the intra-rater reliability of the pedal-ing speed in the VR speedometer mode was good (ICC [intraclass correlation coefficient] = 0.685). The results of the Pearson correlation analysis revealed a significant moderate positive correlation between the pedaling speed of the VR speedometer and the peak torque of knee isokinetic flexion (r = 0.639) and extension (r = 0.598).Conclusion: This study suggests the potential benefits of measuring the maximum pedal-ing speed using 3D depth camera in a VR environment as an indirect assessment of muscle strength. However, technological improvements must be followed to obtain more accurate estimation of muscle strength from the VR cycling test.

Abstract Background Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition that can lead to severe impairment of physical, psychological, cognitive, social, and occupational functions. The cause of ME/CFS remains incompletely understood. There is no clinical diagnostic test for ME/CFS. Although many therapies have been used off-label to manage symptoms of ME/CFS, there are limited, if any, specific therapies or cure for ME/CFS. In this study, we investigated the expression of genes specific to key immune functions, and viral infection status in ME/CFS patients with an aim of identifying biomarkers for characterization and/or treatment of the disease. Methods In 2021, one-hundred and sixty-six (166) patients diagnosed with ME/CFS and 83 healthy controls in the US participated in this study via a social media-based application (app). The patients and heathy volunteers consented to the study and provided self-collected finger-stick blood and first morning void urine samples from home. RNA from the fingerstick blood was tested using DxTerity’s 51-gene autoimmune RNA expression panel (AIP). In addition, DNA from the same fingerstick blood sample was extracted to detect viral load of 4 known ME/CFS associated viruses (HHV6, HHV7, CMV and EBV) using a real-time PCR method. Results Among the 166 ME/CFS participants in the study, approximately half (49%) of the ME/CFS patients reported being house-bound or bedridden due to severe symptoms of the disease. From the AIP testing, ME/CFS patients with severe, bedridden conditions displayed significant increases in gene expression of IKZF2, IKZF3, HSPA8, BACH2, ABCE1 and CD3D, as compared to patients with mild to moderate disease conditions. These six aforementioned genes were further upregulated in the 22 bedridden participants who suffer not only from ME/CFS but also from other autoimmune diseases. These genes are involved in T cell, B cell and autoimmunity functions. Furthermore, IKZF3 (Aiolos) and IKZF2 (Helios), and BACH2 have been implicated in other autoimmune diseases such as systemic lupus erythematosus (SLE) and Rheumatoid Arthritis (RA). Among the 240 participants tested with the viral assays, 9 samples showed positive results (including 1 EBV positive and 8 HHV6 positives). Conclusions Our study indicates that gene expression biomarkers may be used in identifying or differentiating subsets of ME/CFS patients having different levels of disease severity. These gene targets may also represent opportunities for new therapeutic modalities for the treatment of ME/CFS. The use of social media engaged patient recruitment and at-home sample collection represents a novel approach for conducting clinical research which saves cost, time and eliminates travel for office visits.

Activation of ESCRT-mediated cell membrane repair can reduce the extent of tumor cell pyroptosis. Here the authors develop two formulations (an injectable hydrogel and a cell patch) for the sustained release of a Gasdermin-D bacteria-based delivery system and of biodegradable nanoparticles loaded with an ESCRT inhibitor, triggering pyroptosis and antitumor immune responses in preclinical cancer models.

Manipulating the redox chemistry of transition metal dichalcogenides still faces challenges. Here the authors report that tensile-strained MoSe2 can pass on the strain to its sodiated product Mo, and thus regulate the Gibbs free energy in the charging process to enable the reversible sodium storage.

Accurate drug delivery to the lesion has been deliberated for several decades, but one important phenomenon is usually neglected that the immune system can prevent smooth transportation of nanomedicine. Although injection would reduce first-pass effect, macrophages in the blood can still recognize and phagocytose nanomedicine. Here we show that a lubricated nanocontainer, which is prepared based on polyelectrolytes and mesoporous silica nanoparticles, can accurately target muscarinic bioreceptor while escaping from the identification of macrophages. Through in vitro and in vivo studies, this nanocontainer, combining both immune escape and bioreceptor targeting, has greatly improved the drug bioavailability. Additionally, this nanocontainer shows good biocompatibility, and the targeted heart tissues and other important metabolic organs, such as liver and kidney, keep physiological structures and functions without the detection of side effects. Furthermore, the mechanism of immune escape for the developed nanocontainer has been investigated by lubrication test and molecular simulation. We anticipate that our study will establish a new perspective on the achievement of immune escape-based targeted drug delivery, which can provide a fundamental approach for the design of related biomaterials.