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Abstract This study aimed to develop and validate prediction models to estimate the risk of death and intensive care unit admission in COVID-19 inpatients. All RT-PCR-confirmed adult COVID-19 inpatients admitted to Fujian Provincial Hospital from October 2022 to April 2023 were considered. Elastic Net Regression was used to derive the risk prediction models. Potential risk factors were considered, which included demographic characteristics, clinical symptoms, comorbidities, laboratory results, treatment process, prognosis. A total of 1906 inpatients were included finally by inclusion/exclusion criteria and were divided into derivation and test cohorts in a ratio of 8:2, where 1526 (80%) samples were used to develop prediction models under a repeated cross-validation framework and the remaining 380 (20%) samples were used for performance evaluation. Overall performance, discrimination and calibration were evaluated in the validation set and test cohort and quantified by accuracy, scaled Brier score (SbrS), the area under the ROC curve (AUROC), and Spiegelhalter-Z statistics. The models performed well, with high levels of discrimination (AUROCICU [95%CI]: 0.858 [0.803,0.899]; AUROCdeath [95%CI]: 0.906 [0.850,0.948]); and good calibrations (Spiegelhalter-Z ICU : − 0.821 (p-value: 0.412); Spiegelhalter-Z death : 0.173) in the test set. We developed and validated prediction models to help clinicians identify high risk patients for death and ICU admission after COVID-19 infection.

Intracerebral hemorrhage (ICH) is the second most common subtype of stroke, characterized by high mortality and a poor prognosis. Despite various treatment methods, there has been limited improvement in the prognosis of ICH over the past decades. Therefore, it is imperative to identify a feasible treatment strategy for ICH. Mitochondria are organelles present in most eukaryotic cells and serve as the primary sites for aerobic respiration and energy production. Under unfavorable cellular conditions, mitochondria can induce changes in permeability through the opening of the mitochondrial permeability transition pore (mPTP), ultimately leading to mitochondrial dysfunction and contributing to various diseases. Recent studies have demonstrated that mPTP plays a role in the pathological processes associated with several neurodegenerative diseases including Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, ischemic stroke and ischemia-reperfusion injury, among others. However, there is limited research on mPTP involvement specifically in ICH. Therefore, this study comprehensively examines the pathological processes associated with mPTP in terms of oxidative stress, apoptosis, necrosis, autophagy, ferroptosis, and other related mechanisms to elucidate the potential mechanism underlying mPTP involvement in ICH. This research aims to provide novel insights for the treatment of secondary injury after ICH.

Abstract Butyric acid is a volatile saturated monocarboxylic acid, which is widely used in the chemical, food, pharmaceutical, energy, and animal feed industries. This study focuses on producing butyric acid from pre-treated rape straw using simultaneous enzymatic hydrolysis semi-solid fermentation (SEHSF). Clostridium beijerinckii BRM001 screened from pit mud of Chinese nongxiangxing baijiu was used. The genome of C. beijerinckii BRM001 was sequenced and annotated. Using rape straw as the sole carbon source, fermentation optimization was carried out based on the genomic analysis of BRM001. The optimized butyric acid yield was as high as 13.86 ± 0.77 g/L, which was 2.1 times higher than that of the initial screening. Furthermore, under optimal conditions, non-sterile SEHSF was carried out, and the yield of butyric acid was 13.42 ± 0.83 g/L in a 2.5-L fermentor. This study provides a new approach for butyric acid production which eliminates the need for detoxification of straw hydrolysate and makes full use of the value of fermentation waste residue without secondary pollution, making the whole process greener and more economical, which has a certain industrial potential. Graphical Abstract

Abstract Background Secondary immunodeficiency can arise from various clinical conditions that include HIV infection, chronic diseases, malignancy and long-term use of immunosuppressives, which makes the suffering patients susceptible to all types of pathogenic infections. Other than HIV infection, the possible pathogen profiles in other aetiology-induced secondary immunodeficiency are largely unknown. Methods Medical records of the patients with secondary immunodeficiency caused by various aetiologies were collected from the First Affiliated Hospital of Nanchang University, China. Based on these records, models were developed with the machine learning method to predict the potential infectious pathogens that may inflict the patients with secondary immunodeficiency caused by various disease conditions other than HIV infection. Results Several metrics were used to evaluate the models’ performance. A consistent conclusion can be drawn from all the metrics that Gradient Boosting Machine had the best performance with the highest accuracy at 91.01%, exceeding other models by 13.48, 7.14, and 4.49% respectively. Conclusions The models developed in our study enable the prediction of potential infectious pathogens that may affect the patients with secondary immunodeficiency caused by various aetiologies except for HIV infection, which will help clinicians make a timely decision on antibiotic use before microorganism culture results return.

Abstract Background (Pro)renin receptor (PRR) is highly expressed in renal tubules, which is involved in physiological and pathological processes. However, the role of PRR, expressed in renal tubular epithelial cells, in diabetic kidney disease (DKD) remain largely unknown. Methods In this study, kidney biopsies, urine samples, and public RNA-seq data from DKD patients were used to assess PRR expression and cell pyroptosis in tubular epithelial cells. The regulation of tubular epithelial cell pyroptosis by PRR was investigated by in situ renal injection of adeno-associated virus9 (AAV9)-shRNA into db/db mice, and knockdown or overexpression of PRR in HK-2 cells. To reveal the underlined mechanism, the interaction of PRR with potential binding proteins was explored by using BioGrid database. Furthermore, the direct binding of PRR to dipeptidyl peptidase 4 (DPP4), a pleiotropic serine peptidase which increases blood glucose by degrading incretins under diabetic conditions, was confirmed by co-immunoprecipitation assay and immunostaining. Results Higher expression of PRR was found in renal tubules and positively correlated with kidney injuries of DKD patients, in parallel with tubular epithelial cells pyroptosis. Knockdown of PRR in kidneys significantly blunted db/db mice to kidney injury by alleviating renal tubular epithelial cells pyroptosis and the resultant interstitial inflammation. Moreover, silencing of PRR blocked high glucose-induced HK-2 pyroptosis, whereas overexpression of PRR enhanced pyroptotic cell death of HK-2 cells. Mechanistically, PRR selectively bound to cysteine-enrich region of C-terminal of DPP4 and augmented the protein abundance of DPP4, leading to the downstream activation of JNK signaling and suppression of SIRT3 signaling and FGFR1 signaling, and then subsequently mediated pyroptotic cell death. Conclusions This study identified the significant role of PRR in the pathogenesis of DKD; specifically, PRR promoted tubular epithelial cell pyroptosis via DPP4 mediated signaling, highlighting that PRR could be a promising therapeutic target in DKD.

Abstract Background With the arrival of the era of large-scale production, sharing and application of data, digital use has gradually changed people’s daily entertainment, consumption, social interaction, learning and other behaviors in its efficient form. This paper mainly discusses whether this fast and convenient behavior leads Chinese older adults to adopt healthier lifestyles. Methods Using the most recent information from the Chinese Family Panel Studies (CFPS) in 2020, this paper conducted a descriptive statistical analysis on the basic situation of digital use and lifestyles among Chinese older adults and used a structural equation model to analyse the influence of frequency and types of digital use in a variety of different aspects of the real life of Chinese older adults. Results Research revealed that the quality of life of Chinese older adults improved significantly as a result of their use of digital technology. The frequency of digital use (FDU) significantly improved Chinese older adults’ diet, sleep, exercise, smoking and drinking, and relieved their depression. The types of digital use (TDU) had a significant positive correlation with the lifestyle of Chinese older adults, especially in the influence of digital entertainment (DE), digital consumption (DC) and digital social interaction (DI) on the lifestyle of Chinese older adults. Conclusions Digital use can improve the health of Chinese older adults by promoting a healthy lifestyle through various means. The findings of this study have a substantial positive impact on bridging the digital divide that Chinese older adults face, as well as fostering the integration of digital use into their healthy lifestyles.

ObjectiveThere is currently a lack of evidence in evidence-based medicine regarding acupuncture treatment for experimental intracerebral hemorrhage (ICH). The aim of this study was to systematically evaluate the efficacy of acupuncture treatment for experimental ICH based on neurological function scores and brain water content (BWC).MethodsEight mainstream Chinese and English databases were searched. Outcome measures included neurological function scores and BWC, and subgroup analysis was conducted based on study characteristics.ResultsA total of 32 studies were included. Meta-analysis results indicated that compared to the control group, the acupuncture group showed significant reductions in mNSS (MD = −3.16, p

Establishing robust correspondences between two images is important for computer version tasks. However, in the real scene incorrect correspondences are inevitable no matter what kind of correspondence matching algorithms are adopted due to some complex factors, such as illumination, occlusion, and so on. To reduce the number of incorrect correspondences, an algorithm with the same object and same position constraints (SOSPC), is proposed to remove wrong correspondences from the given putative correspondences in this paper. The algorithm is based on the fact that in the given image pairs correct correspondences locate at the same position on the same objects. To select the correspondences on the same objects, an object matching method based on the correspondences selected by GMS is proposed. To select the correspondences on the correct positions, an iterative fundamental matrix estimation method based on clustering is presented. The experimental results have validated the effectiveness of the same object and the same position constraints, and the method achieves the state-of-art performance on five datasets.

Based on the unique insulator-metal phase transition property of vanadium dioxide (VO2), we propose an integrated metasurface with a switchable mechanism between ultra-broadband absorption and polarization conversion, operating in the terahertz (THz) frequency range. The designed metasurface device is constructed using a stacked structure composed of VO2 quadruple rings, a dielectric layer, copper stripes, VO2 film, a dielectric layer, and a copper reflection layer. Our numerical simulations demonstrate that our proposed design, at high temperatures (above 358 K), exhibits an ultra-broadband absorption ranging from 4.95 to 18.39 THz, maintaining an absorptivity greater than 90%, and achieves a relative absorption bandwidth of up to 115%, significantly exceeding previous research records. At room temperature (298 K), leveraging VO2’s insulating state, our proposed structure transitions into an effective polarization converter, without any alteration to its geometry. It enables efficient conversion between orthogonal linear polarizations across 3.51 to 10.26 THz, with cross-polarized reflection exceeding 90% and a polarization conversion ratio over 97%. More importantly, its relative bandwidth reaches up to 98%. These features highlight its wide-angle, extensive bandwidth, and high-efficiency advantages for both switching functionalities. Such an ultra-broadband convertible design offers potential applications in optical switching, temperature dependent optical sensors, and other tunable THz devices in various fields.

With the aging of the population, the health of the elderly has become increasingly important. Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients following general anesthesia or surgery. It is characterized by cognitive decline that may persist for weeks, months, or even longer. Electroacupuncture (EA), a novel therapy that combines physical nerve stimulation with acupuncture treatment from traditional Chinese medicine, holds potential as a therapeutic intervention for preventing and treating POCD, particularly in elderly patients. Although the beneficial effects of EA on POCD have been explored in preclinical and clinical studies, the reliability of EA is limited by methodological shortcomings, and the underlying mechanisms remain largely unexplored. Therefore, we have synthesized existing evidence and proposed potential biological mechanisms underlying the effects of EA on neuroinflammation, oxidative stress, autophagy, the microbiota-gut-brain axis, and epigenetic modification. This review summarizes recent advances in EA and POCD, provides a theoretical foundation, explores potential molecular mechanisms for the prevention and treatment of POCD, and offers a basis for conducting relevant clinical trials.

Intracerebral hemorrhagic stroke, characterized by acute hemorrhage in the brain, has a significant clinical prevalence and poses a substantial threat to individuals’ well-being and productivity. Recent research has elucidated the role of gut microorganisms and their metabolites in influencing brain function through the microbiota-gut-brain axis (MGBA). This article provides a comprehensive review of the current literature on the common metabolites, short-chain fatty acids (SCFAs) and trimethylamine-N-oxide (TMAO), produced by gut microbiota. These metabolites have demonstrated the potential to traverse the blood–brain barrier (BBB) and directly impact brain tissue. Additionally, these compounds have the potential to modulate the parasympathetic nervous system, thereby facilitating the release of pertinent substances, impeding the buildup of inflammatory agents within the brain, and manifesting anti-inflammatory properties. Furthermore, this scholarly analysis delves into the existing dearth of investigations concerning the influence of gut microorganisms and their metabolites on cerebral functions, while also highlighting prospective avenues for future research.

Intracerebral hemorrhage (ICH) manifests precipitously and profoundly impairs the neurological function in patients who are affected. The etiology of subsequent injury post-ICH is multifaceted, characterized by the intricate interplay of various factors, rendering therapeutic interventions challenging. Astrocytes, a distinct class of glial cells, interact with neurons and microglia, and are implicated in a series of pathophysiological alterations following ICH. A comprehensive examination of the functions and mechanisms associated with astrocytic proteins may shed light on the role of astrocytes in ICH pathology and proffer innovative therapeutic avenues for ICH management.

BackgroundPost-stroke depression is a common complication of stroke, with a high incidence rate and low recognition rate. Many patients do not receive effective intervention at the onset, which affects subsequent treatment outcomes. Post-stroke depression not only impacts the patient's mental well-being but also increases the risk of stroke recurrence and poor prognosis. Therefore, it has become a significant public health concern. Acupuncture has gained significant popularity in the treatment of post-stroke depression. However, there are inconsistent clinical research results regarding its efficacy and safety. This systematic review aims to gather and critically assess all available evidence regarding the effectiveness and safety of acupuncture in the treatment of post-stroke depression in patients.MethodsWe will conduct thorough searches for relevant studies in multiple electronic databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP Database, Wan-fang Data and China Biomedical Database). Our search scope will encompass studies published from the inception of each database until September 2023. To evaluate the potential bias in all the included studies, we will adhere to the guidelines offered in the Cochrane Handbook. The total effective rate will be the primary outcome. To conduct a systematic review, we will employ RevMan 5.4 software.ResultsThis study will obtain efficacy and safety of acupuncture for the treatment of post-stroke depression.ConclusionsThe conclusions of this study will provide evidence-based perspectives that can guide clinical decision-making regarding the practicality and recommended timing of using acupuncture to treat post-stroke depression. Furthermore, this study will help advance the clinical application of acupuncture treatment for post-stroke depression and enhance its efficacy while ensuring patient safety.

ObjectiveInflammation participates in the pathology and progression of secondary brain injury after intracerebral hemorrhage (ICH). This meta-analysis intended to explore the prognostic role of inflammatory indexes, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), white blood cell (WBC), and C-reactive protein (CRP) in ICH patients.MethodsEmbase, PubMed, Web of Science, and Cochrane Library were searched until June 2023. Two outcomes, including poor outcome and mortality were extracted and measured. Odds ratio (OR) and 95% confidence interval (CI) were presented for outcome assessment.ResultsForty-six studies with 25,928 patients were included in this meta-analysis. The high level of NLR [OR (95% CI): 1.20 (1.13–1.27), p

The bone is one of the most commonly affected organs in sickle cell disease (SCD). Repeated ischemia, oxidative stress and inflammation within the bone is largely responsible for promoting bone pain. As more individuals with SCD survive into adulthood, they are likely to experience a synergistic impact of both aging and SCD on their bone health. As bone health deteriorates, bone pain will likely exacerbate. Recent mechanistic and observational studies emphasize an intricate relationship between bone remodeling and the peripheral nervous system. Under pathological conditions, abnormal bone remodeling plays a key role in the propagation of bone pain. In this review, we first summarize mechanisms and burden of select bone complications in SCD. We then discuss processes that contribute to pathological bone pain that have been described in both SCD as well as non-sickle cell animal models. We emphasize the role of bone-nervous system interactions and pitfalls when designing new therapies especially for the sickle cell population. Lastly, we also discuss future basic and translational research in addressing questions about the complex role of stress erythropoiesis and inflammation in the development of SCD bone complications, which may lead to promising therapies and reduce morbidity in this vulnerable population.

In this paper, experimental and numerical studies were conducted to differentiate solvent exsolution and liberation processes from different heavy oil–solvent systems in bulk phases and porous media. Experimentally, two series of constant-composition-expansion (CCE) tests in a PVT cell and differential fluid production (DFP) tests in a sandpacked model were performed and compared in the heavy oil–CO2, heavy oil–CH4, and heavy oil–C3H8 systems. The experimental results showed that the solvent exsolution from each heavy oil–solvent system in the porous media occurred at a higher pressure. The measured bubble-nucleation pressures (Pn) of the heavy oil–CO2 system, heavy oil–CH4 system, and heavy oil–C3H8 system in the porous media were 0.24 MPa, 0.90 MPa, and 0.02 MPa higher than those in the bulk phases, respectively. In addition, the nucleation of CH4 bubbles was found to be more instantaneous than that of CO2 or C3H8 bubbles. Numerically, a robust kinetic reaction model in the commercial CMG-STARS module was utilized to simulate the gas exsolution and liberation processes of the CCE and DFP tests. The respective reaction frequency factors for gas exsolution (rffe) and liberation (rffl) were obtained in the numerical simulations. Higher values of rffe were found for the tests in the porous media in comparison with those in the bulk phases, suggesting that the presence of the porous media facilitated the gas exsolution. The magnitudes of rffe for the three different heavy oil–solvent systems followed the order of CO2 > CH4 > C3H8 in the bulk phases and CH4 > CO2 > C3H8 in the porous media. Hence, CO2 was exsolved from the heavy oil most readily in the bulk phases, whereas CH4 was exsolved from the heavy oil most easily in the porous media. Among the three solvents, CH4 was also found most difficult to be liberated from the heavy oil in the DFP test with the lowest rffl of 0.00019 min−1. This study indicates that foamy-oil evolution processes in the heavy oil reservoirs are rather different from those observed from the bulk-phase tests, such as the PVT tests.

In this study, we conducted an extensive investigation into broadband near-infrared luminescence of Cr3+-doped Ca3Y2Ge3O12 garnet, employing first-principles calculations within the density functional theory framework. Our initial focus involved determining the site occupancy of Cr3+ activator ions, which revealed a pronounced preference for the Y3+ sites over the Ca2+ and Ge4+ sites, as evidenced by the formation energy calculations. Subsequently, the geometric structures of the excited states 2E and 4T2, along with their optical transition energies relative to the ground state 4A2 in Ca3Y2Ge3O12:Cr3+, were successfully modeled using the ΔSCF method. Calculation convergence challenges were effectively addressed through the proposed fractional particle occupancy schemes. The constructed host-referred binding energy diagram provided a clear description of the luminescence kinetics process in the garnet, which explained the high quantum efficiency of emission. Furthermore, the accurate prediction of thermal excitation energy yielded insights into the thermal stability of the compound, as illustrated in the calculated configuration coordinate diagram. More importantly, all calculated data were consistently aligned with the experimental results. This research not only advances our understanding of the intricate interplay between geometric and electronic structures, optical properties, and thermal behavior in Cr3+-doped garnets but also lays the groundwork for future breakthroughs in the high-throughput design and optimization of luminescent performance and thermal stability in Cr3+-doped phosphors.

The pulse-width modulation (PWM) variable spray system is the most widely used variable spray system in the world at present, which has the characteristics of a fast response, large flow adjustment range, and good atomization. Recently, the pressure fluctuation and droplet deposition uniformity of the PWM variable spray system caused by the intermittent spray mode of the nozzle have attracted more and more attention. In this study, a method for eliminating the inhomogeneity of ground deposition in low-frequency PWM variable sprays based on a staggered-phase drive mode was proposed, and a PWM variable spray system was built. The experimental results indicated that the pressure fluctuation amplitude upstream of the nozzle of the PWM variable spray system with the staggered-phase drive was reduced by 40.91%, and the dispersion rate of the pressure fluctuation was reduced by 62.78% (the initial pressure was 0.3 MPa, solenoid valve frequency was 5 Hz, and duty cycle was 50%). The PWM control parameters had a significant effect on the upstream pressure fluctuation (initial pressure > duty cycle > frequency). The droplet spectrum relative span of the staggered phased PWM variable spray system decreased by 24.83%, the coefficient of variation of the droplet particle size decreased by 4.40%, the particle size was more uniform, and the atomization effect was improved. The average deposition of droplets in the forward direction driven by the staggered phase was 4.87% greater than that in the same phase, and the variation rate decreased by 20.87%. The average deposition amount increased, and the deposition became more uniform. Staggered-phase spray control could effectively reduce the inhomogeneity of deposition in low-frequency PWM intermittent spraying. This research provides strong technical support for a precision variable spraying effect and droplet drift prevention.

Benzene, a known toxic, carcinogenic, and pervasively present environmental pollutant, necessitates effective monitoring strategies to assess human exposure. S-Phenylmercapturic acid (S-PMA) is a specific biomarker for benzene exposure. This study presents a point-of-care testing (POCT) assay for the detection of S-PMA in human urine, integrating salt-induced phase separation (SIPS) with surface-enhanced Raman spectroscopy (SERS). S-PMA in human urine was first effectively separated using SIPS and then detected using a portable Raman spectrometer employing Au colloids as the SERS substrate. The POCT assay exhibited a clear correlation between the signal intensity and logarithmic concentration of S-PMA (0-5 ppm), demonstrating satisfactory recovery and reproducibility. Moreover, high-throughput fingerprint identification and quantitative analysis of S-PMA in urine were achieved within 10 min, with a detection limit as low as 1.06 ppb, by performing SIPS-SERS on 96-well plates. This POCT method holds promise for personal exposure assessment and may potentially aid in the prevention of benzene-induced diseases. [ABSTRACT FROM AUTHOR]

A gel based on polyacrylamide, exhibiting delayed crosslinking characteristics, emerges as the preferred solution for mitigating degradation under conditions of high temperature and extended shear in ultralong wellbores. High viscosity/viscoelasticity of the fracturing fluid was required to maintain excellent proppant suspension properties before gelling. Taking into account both the cost and the potential damage to reservoirs, polymers with lower concentrations and molecular weights are generally preferred. In this work, the supramolecular action was integrated into the polymer, resulting in significant increases in the viscosity and viscoelasticity of the synthesized supramolecular polymer system. The double network gel, which is formed by the combination of the supramolecular polymer system and a small quantity of Zr-crosslinker, effectively resists temperature while minimizing permeability damage to the reservoir. The results indicate that the supramolecular polymer system with a molecular weight of (268-380) ×104 g/mol can achieve the same viscosity and viscoelasticity at 0.4 wt% due to the supramolecular interaction between polymers, compared to the 0.6 wt% traditional polymer (hydrolyzed polyacrylamide, molecular weight of 1078 ×104 g/mol). The supramolecular polymer system possessed excellent proppant suspension properties with a 0.55 cm/min sedimentation rate at 0.4 wt%, whereas the 0.6 wt% traditional polymer had a rate of 0.57 cm/min. In comparison to the traditional gel with a Zrcrosslinker concentration of 0.6 wt% and an elastic modulus of 7.77 Pa, the double network gel with a higher elastic modulus (9.00 Pa) could be formed only at 0.1 wt% Zr-crosslinker, which greatly reduced the amount of residue of the fluid after gel-breaking. The viscosity of the double network gel was 66 mPa s after 2 h shearing, whereas the traditional gel only reached 27 mPa s. [ABSTRACT FROM AUTHOR]

Developing highly efficient and low-cost photoelectrocatalyst for H2 evolution under visible-light irradiation is a key topic in the areas of energy and environment. In this work, we designed and deposited p-type semiconductor Cu3N onto 1D n-type rutile TiO2 nanorod array by the magnetron sputtering method. The formed TiO2/Cu3N p-n heterojunction not only exhibits a narrowed band gap from 3.09 eV for TiO2 to 2.01 eV for TiO2/Cu3N but also expands the light-response from UV to visiblelight region. In addition, the lifetime, separation and transfer of the photogenerated electron-hole pairs are efficiently prolonged and improved due to the build-in electric field at the interface of the TiO2/Cu3N p-n heterojunction. As a result, the photocurrent density under 4420 nm visible-light irradiation is enhanced for about 14.12 times, from 0.33 mA cm2 for TiO2 to 4.66 mA cm2 for TiO2/Cu3N at 0.97 V vs. RHE (reversible hydrogen electrode). Furthermore, the constructed TiO2/Cu3N heterojunction shows stable PEC H2 evolution performance, with the H2 production rate reaching 6.98 mmol cm2 h1 under 4420 nm visible-light irradiation. Our results suggest that the construction of nontoxic p-n heterojunction with suitable band gap should be a promising strategy to improve the photoelectrocatalytic performance of TiO2 and should be applied in other photoelectrocatalysts. [ABSTRACT FROM AUTHOR]

The bone is one of the most commonly affected organs in sickle cell disease (SCD). Repeated ischemia, oxidative stress and inflammation within the bone is largely responsible for promoting bone pain. As more individuals with SCD survive into adulthood, they are likely to experience a synergistic impact of both aging and SCD on their bone health. As bone health deteriorates, bone pain will likely exacerbate. Recent mechanistic and observational studies emphasize an intricate relationship between bone remodeling and the peripheral nervous system. Under pathological conditions, abnormal bone remodeling plays a key role in the propagation of bone pain. In this review, we first summarize mechanisms and burden of select bone complications in SCD. We then discuss processes that contribute to pathological bone pain that have been described in both SCD as well as non-sickle cell animal models. We emphasize the role of bone-nervous system interactions and pitfalls when designing new therapies especially for the sickle cell population. Lastly, we also discuss future basic and translational research in addressing questions about the complex role of stress erythropoiesis and inflammation in the development of SCD bone complications, which may lead to promising therapies and reduce morbidity in this vulnerable population. [ABSTRACT FROM AUTHOR]

Compared to either HIV or hepatitis B virus (HBV) monoinfected individuals, HIV/HBV-coinfected individuals have a decreased probability of spontaneous HBV clearance and a greater risk of developing chronic liver damage and a faster progression to cirrhosis and hepatocellular carcinoma. This manuscript attempts to provide a comprehensive review of the landscape of current HIV/HBV coinfection research with a focus on the intricate interactions between these two viruses. Our review will help understand the disease dynamics of HIV/HBV coinfection and has important implications for designing public health strategies. [ABSTRACT FROM AUTHOR]

Abstract Background Cardiopulmonary bypass (CPB) results in brain injury, which is primarily caused by inflammation. Ac2-26 protects against ischemic or hemorrhage brain injury. The present study was to explore the effect and mechanism of Ac2-26 on brain injury in CPB rats. Methods Forty-eight rats were randomized into sham, CPB, Ac, Ac/AKT1, Ac/GSK3βi and Ac/AKT1/GSK3βa groups. Rats in sham group only received anesthesia and in the other groups received standard CPB surgery. Rats in the sham and CPB groups received saline, and rats in the Ac, Ac/AKT1, Ac/GSK3βi and Ac/AKT1/GSK3βa groups received Ac2-26 immediately after CPB. Rats in the Ac/AKT1, Ac/GSK3βi and Ac/AKT1/GSK3βa groups were injected with shRNA, inhibitor and agonist of GSK3β respectively. The neurological function score, brain edema and histological score were evaluated. The neuronal survival and hippocampal pyroptosis were assessed. The cytokines, activity of NF-κB, S100 calcium-binding protein β(S100β) and neuron-specific enolase (NSE), and oxidative were tested. The NLRP3, cleaved-caspase-1 and cleaved-gadermin D (GSDMD) in the brain were also detected. Results Compared to the sham group, all indicators were aggravated in rats that underwent CPB. Compared to the CPB group, Ac2-26 significantly improved neurological scores and brain edema and ameliorated pathological injury. Ac2-26 reduced the local and systemic inflammation, oxidative stress response and promoted neuronal survival. Ac2-26 reduced hippocampal pyroptosis and decreased pyroptotic proteins in brain tissue. The protection of Ac2-26 was notably lessened by shRNA and inhibitor of GSK3β. The agonist of GSK3β recovered the protection of Ac2-26 in presence of shRNA. Conclusions Ac2-26 significantly improved neurological function, reduced brain injury via regulating inflammation, oxidative stress response and pyroptosis after CPB. The protective effect of Ac2-26 primarily depended on AKT1/ GSK3β pathway.

Background: No single risk factor is decisive in shaping an individual's healthy development. This study aimed to analyze the relationship between depressive symptoms and a cumulative risk index comprising individual, family, and social variables among nursing students. Methods: We enrolled 1716 Chinese nursing students from three universities in a paperless survey that assessed a range of individual, family, and social risk factors associated with depressive symptoms. Multiple risk analysis was conducted to create a composite risk score for each individual. A test for trend was employed to assess the relationship between the multiple risk classification and depressive symptoms individually. Additionally, a 2-step cluster analysis and χ2 tests were used to examine the relationship between the different clusters and the level of depressive symptoms. Results: The mean scores of depressive symptoms increased significantly as the number of risk factors increased, regardless of their combination. As the number of risk factors increased, the proportion of nursing students in the normal group decreased, while the proportion in the group with depressive symptoms of varying severity tended to increase (P

Zika virus (ZIKV) and Japanese encephalitis virus (JEV) are antigenically related flaviviruses that co-circulate in many countries/territories. The interaction between the two viruses needs to be determined. Recent findings by ourselves and other labs showed that JEV-elicited antibodies (Abs) and CD8+ T cells exacerbate and protect against subsequent ZIKV infection, respectively. However, the impact of JEV envelope (E) protein domain III (EDIII)-induced immune responses on ZIKV infection is unclear. We show here that sera from JEV-EDIII-vaccinated mice cross-react with ZIKV-EDIII in vitro, and transfer of the same sera to mice significantly decreases death upon lethal ZIKV infection at a dose-dependent manner. Maternally acquired anti-JEV-EDIII Abs also significantly reduce the mortality of neonatal mice born to JEV-EDIII-immune mothers post ZIKV challenge. Similarly, transfer of ZIKV-EDIII-reactive IgG purified from JEV-vaccinated humans increases the survival of ZIKV-infected mice. Notably, transfer of an extremely low volume of JEV-EDIII-immune sera or ZIKV-EDIII-reactive IgG does not mediate the Ab-mediated enhancement (ADE) of ZIKV infection. Similarly, transfer of JEV-EDIII-elicited CD8+ T cells protects recipient mice against ZIKV challenge. These results demonstrate that JEV-EDIII-induced immune components including Abs and T cells have protective roles in ZIKV infection, suggesting EDIII is a promising immunogen for developing effective and safety JEV vaccine.