Metagenomic next-generation sequencing for the diagnosis of neurobrucellosis.

Objective: This study investigates the application of metagenomic next-generation sequencing (mNGS) in the diagnosis of neurobrucellosis (NB). Methods: We retrospectively analyzed patients diagnosed with NB who underwent cerebrospinal fluid (CSF) mNGS testing in Xijing Hospital from 2015 to 2021. Results: Among the 20 individuals included in the study, the serum rose bengal test was positive in 11 out of 16 cases, serum agglutination test was positive in 13 out of 16 cases, CSF culture was positive in 6 out of 11 cases, and CSF mNGS tests were positive in 18 out of 20 cases. Conclusion: CSF mNGS demonstrates superior sensitivity; therefore, it is recommended to collect CSF for mNGS testing prior to antibiotic therapy when NB is suspected.

Neurobrucellosis (NB) is a disease of the nervous system caused by a type of bacteria called Brucella. It is rare, serious and manifests inconsistently, making it hard to diagnose. Metagenomic next-generation sequencing (mNGS) is a new way to detect disease-causing bacteria by looking at their genetic material. mNGS is fast, accurate and covers a wide range of disease-causing bacteria. We looked back at patients diagnosed with NB at Xijing Hospital between 2015 and 2021 and tested samples of the fluid surrounding the brain and the spinal cord, called cerebrospinal fluid (CSF), by mNGS. A total of 20 patients were included in the study. Compared with the traditional methods, mNGS of CSF samples showed advantages in diagnosing NB. However, antibiotics may affect the results.

Abnormal Bone Turnover Observed in Obese Children Based on Puberty Stage -Specific Bone Turnover Marker Reference.

CONTEXT: Childhood and adolescence are critical periods for lifelong bone health. The impact of obesity on these phases is controversial, which may be due to the lack of standards for age-, sex-, and puberty-specific Bone turnover markers (BTMs) which could sensitively reflect bone metabolism. OBJECTIVE: To generate age-, sex, and puberty stage-specific BTMs reference curves in children and adolescents and to explore the effect of obesity on bone metabolism in the Chinese population. METHODS: Our study was part of the Evaluation and Monitoring on School-based Nutrition and Growth in Shenzhen study. 800 participants aged 6∼18 years with normal body mass index (BMI) were selected to establish BTM reference curves for boys and girls at different ages under different pubertal development stages. Additionally, 200 participants with obesity (BMI >P95th) were matched with healthy children from the original cohort at a 1:1 ratio. All participants underwent bone mineral density assessment, and serum levels of P1NP and ß-CTX were measured. RESULTS: The BTMs values presented significant age, sex, and puberty stage differences. Analysis of serum BTMs based on the established reference revealed a higher percentage of low-level P1NP in boys with obesity (P=0.005); no significant difference was observed in girls. However, the obese group showed a significantly higher proportion of high ß-CTX levels for girls, not boys (P=0.022). CONCLUSIONS: We provide age-, sex-, and puberty stage-specific P1NP and ß-CTX reference curve. According to these, obesity appeared to be a negative factor for bone formation in boys and for bone resorption in girls.

Spatially ordered NiOOH-ZnS/CdS heterostructures with an efficient photo-carrier transmission channel for markedly improved H2 production.

Spatially-ordered 1D nanocrystal-based semiconductor nanostructures possess distinct merits for photocatalytic reaction, including large surface area, fast carrier separation, and enhanced light scattering and absorption. Nevertheless, establishing a valid photo-carrier transmission channel is still crucial yet challenging for semiconductor heterostructures to realize efficient photocatalysis. In this work, spatially ordered NiOOH-ZnS/CdS heterostructures were constructed by sequential ZnS coating and NiOOH photo-deposition on multi-armed CdS, which consists of {112̄0}-faceted wurtzite nanorods grown epitaxially on {111}-faceted zinc blende core. Intriguingly, the surface photovoltage spectroscopy and PbO2 photo-deposition results suggest that the photogenerated holes of CdS were first transferred to the Zn-vacancy level of ZnS and then to NiOOH, as driven by the built-in electric field between ZnS and CdS and the hole-extracting effect of the NiOOH cocatalyst, leading to the efficient charge separation of NiOOH-ZnS/CdS. With visible-light (λ > 420 nm) irradiation, NiOOH-ZnS/CdS exhibited a distinguished H2-evolution rate of 152.20 mmol g-1 h-1 (apparent quantum efficiency of 40.9% at 420 nm), approximately 18 folds that of 3 wt% Pt-loaded CdS and much higher than that of ZnS/CdS and NiOOH-CdS counterparts as well as the most reported CdS-containing photocatalysts. Moreover, the cycling and long-term H2 generation tests manifested the outstanding photocatalyst stability of NiOOH-ZnS/CdS. The study results presented here may propel the controllable design of highly-active nanomaterials for solar conversion and utilization.

Critical bloodstream infection caused by Chromobacterium violaceum: a case report in a 15-year-old male with sepsis-induced cardiogenic shock and purpura fulminans.

Chromobacterium violaceum (C. violaceum) is a gram-negative bacillus that is widespread in tropical and subtropical areas. Although C. violaceum rarely infects humans, it can cause critical illness with a mortality rate above 50%. Here, we report the successful treatment of a 15-year-old male who presented with bloodstream infection of C. violaceum along with sepsis, specific skin lesions, and liver abscesses. Cardiogenic shock induced by sepsis was reversed by venoarterial extracorporeal membrane oxygenation (VA ECMO). Moreover, C. violaceum-related purpura fulminans, which is reported herein for the first time, was ameliorated after treatment. This case report demonstrates the virulence of C. violaceum with the aim of raising clinical awareness of this disease.

Joint trajectories of loneliness, social isolation and sarcopenia and associations with adverse outcomes: A prospective cohort study.

This study aimed to examine joint trajectories of loneliness, social isolation and sarcopenia and their associations with adverse outcomes. A total of 4701 participants aged ≥60 years who had a baseline and at least one follow-up assessment of loneliness, social isolation and sarcopenia across 2011, 2013 and 2015 waves in China Health and Retirement Longitudinal Study. Adverse outcomes were obtained in 2018 wave. Joint trajectories were fit using the parallel process latent class growth analysis, and their associations with adverse outcomes were evaluated using modified Poisson regression. Joint trajectory patterns for social relationship and sarcopenia did not vary by the assessment for sarcopenia, but did vary by the assessment for social relationship. Older adults exhibit distinct joint trajectories and those with persistent combination of loneliness or social isolation and sarcopenia experience greatest risk of adverse outcomes. These findings implicate integration of health care and social care for community-dwelling older adults.

Cryo-EM Structure of human HCN3 channel and its regulation by cAMP.

HCN channels are important for regulating heart rhythm and nerve activity and have been studied as potential drug targets for treating depression, arrhythmia, nerve pain and epilepsy.Despite possessing unique pharmacological properties, HCN channels share common characteristics in that they are activated by hyperpolarization and modulated by cAMP and other membrane lipids. However, the mechanisms of how these ligands bind and modulate HCN channels are unclear. In this study, we solved structures of full-length human HCN3 using cryo-EM and captured two different states, including a state without any ligand bound and a state with cAMP bound. Our structures reveal the novel binding sites for cholesteryl hemisuccinate in apo-state and show how cholesteryl hemisuccinate and cAMP binding cause conformational changes in different states. These findings explain how these small modulators are sensed in mammals at the molecular level.The results of our study could help design more potent and specific compounds to influence HCN channel activity and offer new therapeutic possibilities for diseases that lack effective treatment.

Evaluating the efficacy of standardized pressure ulcer management protocols in the prevention of pressure injuries among patients undergoing neurosurgical procedures.

Pressure injuries are a significant concern for patients undergoing neurosurgical procedures due to prolonged immobility and the complexity of care. This study evaluates the efficacy of standardized pressure ulcer management protocols in preventing pressure injuries and enhancing patient care in a neurosurgical context. A comprehensive retrospective analysis was conducted at a single institution from December 2020 to December 2023, comparing 50 patients who received standardized pressure ulcer management (intervention group) with 50 patients who received conventional care (control group). The study assessed the incidence of pressure ulcers, patient comfort levels using the Kolcaba Comfort Scale and sleep quality using the Richards-Campbell Sleep Questionnaire (RCSQ). Statistical analysis was performed using SPSS software, version 27.0, applying t-tests and chi-square tests as appropriate. The intervention group exhibited a significantly lower incidence of pressure ulcers at all measured time points post-surgery compared to the control group. Patient comfort levels in the intervention group were consistently higher across psychological, environmental, physiological and socio-cultural domains. Sleep quality metrics, including sleep depth, latency to sleep onset and overall sleep quality, were significantly improved in the intervention group. The implementation of standardized pressure ulcer management protocols in neurosurgical care significantly reduces the incidence of pressure injuries, enhances patient comfort and improves sleep quality. These findings highlight the importance of adopting structured care protocols to improve postoperative outcomes and patient well-being in neurosurgical settings.

A new generation of structural biologists in China.

We have asked young scientists who spoke at our recent Cell Symposium "Structural biology from the nanoscale to cellular mesoscale" in Huangshan, China to tell us more about themselves and their exciting research in this collection of Voices.

Solvent-Induced Bright Emission in Lead-Free Organic-Inorganic Antimony Bromides with Reversible Transformation.

Lead-free low-dimensional organic-inorganic metal halides have gained increasing attention in a wide range of applications due to their low toxicity, outstanding optical performance, and structural tunability. In this work, a general method of incorporating organic molecule into sodium antimony bromides is introduced. The 1D Na3SbBr6(C2H6OS)6 and Na3SbBr6(C4H8OS)6 single crystals exhibit bright yellow and orange emission with PL peaks at 610 and 664 nm, and high photoluminescence quantum yields (PLQYs) of 85% and 60%, respectively. These two compounds can be reversibly converted into each other by the removal and addition of the organic components. Their exceptional luminescent performance enables them to be used as solid-state phosphors for the fabrication of yellow and orange down-conversion LEDs. A white LED with a high color rendering index (CRI) of 95 is also fabricated by using Na3SbBr6(C2H6OS)6 as the yellow phosphor. The universality of this method is demonstrated by synthesizing other members of this family with diverse A-groups, including methylammonium (MA) and formamidinium (FA). This work provides an effective strategy for the development of diverse lead-free and high-performance organic-inorganic hybrid materials and indicates these organic-inorganic hybrid compounds are promising luminescent materials for lighting or displays.

Expression and Clinical Significance of NUDCD1, PI3K/AKT/mTOR Signaling Pathway-Related Molecules and Immune Infiltration in Breast Cancer.

BACKGROUND: NUDCD1 (NudC Domain Containing 1) performs an essential function in biological processes such as cell progression, migration, cell cycle, and intracellular material transport. Many solid tumors express it highly, which is a prospective biomarker and therapeutic approach. However, the expression and clinical importance of NUDCD1 across breast cancer is unclear. METHODS: The expressions of NUDCD1 in breast cancers and normal breast tissues were studied utilizing the TIMER database and immunohistochemical analysis. Subsequently, we validate the association between the expression of NUDCD1 and clinicopathologic features and prognosis of breast cancer. The immunohistochemical experiments of pathway-related molecules were done on 214 breast cancer tissue microarrays. The investigation of correlation between NUDCD1 expression and tumor immune infiltration was subsequently conducted. RESULTS: Through the utilization of bioinformatics analysis and immunohistochemical experiments, it was determined that NUDCD1 exhibited upregulation within breast cancer. Furthermore, it was discovered that an elevated expression of NUDCD1 may potentially be linked to a worse prognosis in breast cancer. Our study reveals that the PI3K/AKT/mTOR signaling pathway may perform a function in NUDCD1 regulating breast cancer progression via enrichment analysis. Furthermore, the expression of NUDCD1 may be associated with the degree of immunological infiltration. CONCLUSION: The expression of NUDCD1 was explored to be elevated in breast cancer and was observed to be correlated with a poorer prognosis. p-AKT, PI3K, AKT, mTOR, and p-mTOR expression levels underwent significant elevation in breast cancer. The function of NUDCD1 within breast cancer might be associated with the PI3K/AKT/mTOR signaling pathway.

Skiing economy and kinematic during a field double poling roller skiing among novice and experienced cross-country skiers.

To assess the skiing economy (SE) and kinematics during double poling (DP) roller skiing between two groups of skiers in a field setting. Five experienced and five novice male skiers performed a SEDP test at 16 km∙h-1 on an outdoor athletics track. Gas exchange parameters were measured to determine SEDP. A two-dimensional video was filmed to measure the kinematics variables. Experienced skiers exhibited a 21% lower oxygen cost than novice skiers (p = 0.016) in DP, indicating a strong association between SEDP, cycle length and cycle rate (p < 0.001). Additionally, before the poling phase, experienced skiers manifested significantly greater maximum hip and knee extension angles than novice skiers (p < 0.001). During the poling phase, experienced skiers with a greater pole plant angle (p = 0.001), longer flexion time (p < 0.001) and higher flexion angular velocity in the elbow joint (p < 0.05) demonstrated better SEDP. There was an interaction effect of the one-repetition maximum bench press × group in SEDP (b = - 0.656, SE = 0.097, t = - 6.78, p = 0.001). Therefore, experienced skiers with better SEDP demonstrated more efficient cycles, potentially accomplished using dynamic full-body DP motion to ascertain effective propulsion. Combined upper body strength and ski-specific skill training may enhance SEDP in novice skiers.

Specific lineage transition of tumor-associated macrophages elicits immune evasion of ascitic tumor cells in gastric cancer with peritoneal metastasis.

BACKGROUND: Gastric cancer with peritoneal metastasis (PM-GC), recognized as one of the deadliest cancers. However, whether and how the tumor cell-extrinsic tumor microenvironment (TME) is involved in the therapeutic failure remains unknown. Thus, this study systematically assessed the immunosuppressive tumor microenvironment in ascites from patients with PM-GC, and its contribution to dissemination and immune evasion of ascites-disseminated tumor cells (aDTCs). METHODS: Sixty-three ascites and 43 peripheral blood (PB) samples from 51 patients with PM-GC were included in this study. aDTCs in ascites and circulating tumor cells (CTCs) in paired PB were immunophenotypically profiled. Using single-cell RNA transcriptional sequencing (scRNA-seq), crosstalk between aDTCs and the TME features of ascites was inspected. Further studies on the mechanism underlying aDTCs-immune cells crosstalk were performed on in vitro cultured aDTCs. RESULTS: Immune cells in ascites interact with aDTCs, prompting their immune evasion. Specifically, we found that the tumor-associated macrophages (TAMs) in ascites underwent a continuum lineage transition from cathepsinhigh (CTShigh) to complement 1qhigh (C1Qhigh) TAM. CTShigh TAM initially attracted the metastatic tumor cells to ascites, thereafter, transitioning terminally to C1Qhigh TAM to trigger overproliferation and immune escape of aDTCs. Mechanistically, we demonstrated that C1Qhigh TAMs significantly enhanced the expression of PD-L1 and NECTIN2 on aDTCs, which was driven by the activation of the C1q-mediated complement pathway. CONCLUSIONS: For the first time, we identified an immunosuppressive macrophage transition from CTShigh to C1Qhigh TAM in ascites from patients with PM-GC. This may contribute to developing potential TAM-targeted immunotherapies for PM-GC.

Investigations of the prognostic value of RUNX1 mutation in acute myeloid leukemia patients: Data from a real-world study.

RUNX1 is one of the recurrent mutated genes in newly diagnosed acute myeloid leukemia (AML). Although historically recognized as a provisional distinct entity, the AML subtype with RUNX1 mutations (AML-RUNX1mut) was eliminated from the 2022 WHO classification system. To gain more insight into the characteristics of AML-RUNX1mut, we retrospectively analyzed 1065 newly diagnosed adult AML patients from the First Affiliated Hospital of Soochow University between January 2017 and December 2021. RUNX1 mutations were identified in 112 patients (10.5%). The presence of RUNX1 mutation (RUNX1mut) conferred a lower composite complete remission (CRc) rate (40.2% vs. 58.4%, P＜0.001), but no significant difference was observed in the 5-year overall survival (OS) rate (50.2% vs. 53.9%; HR=1.293; P=0.115) and event-free survival (EFS) rate (51.5% vs. 49.4%; HR=1.487, P=0.089), even within the same risk stratification. Multivariate analysis showed that RUNX1mut was not an independent prognostic factor for OS (HR=1.352, P=0.068) or EFS (HR=1.129, P=0.513). When patients were stratified according to induction regimen, RUNX1mut was an unfavorable factor for CRc both on univariate and multivariate analysis in patients receiving conventional chemotherapy, and higher risk stratification predicted worse OS. In those who received venetoclax plus hypomethylating agents, RUNX1mut was not predictive of CRc and comparable OS and EFS were seen between intermediate-risk and adverse-risk groups. The results of this study revealed that the impact of RUNX1mut is limited. Its prognostic value depended more on treatment and co-occurrent abnormalities. VEN-HMA may abrogate the prognostic impact of RUNX1, which merits a larger prospective cohort to illustrate.

Large exchange-driven intrinsic circular dichroism of a chiral 2D hybrid perovskite.

In two-dimensional chiral metal-halide perovskites, chiral organic spacers endow structural and optical chirality to the metal-halide sublattice, enabling exquisite control of light, charge, and electron spin. The chiroptical properties of metal-halide perovskites have been measured by transmissive circular dichroism spectroscopy, which necessitates thin-film samples. Here, by developing a reflection-based approach, we characterize the intrinsic, circular polarization-dependent complex refractive index for a prototypical two-dimensional chiral lead-bromide perovskite and report large circular dichroism for single crystals. Comparison with ab initio theory reveals the large circular dichroism arises from the inorganic sublattice rather than the chiral ligand and is an excitonic phenomenon driven by electron-hole exchange interactions, which breaks the degeneracy of transitions between Rashba-Dresselhaus-split bands, resulting in a Cotton effect. Our study suggests that previous data for spin-coated films largely underestimate the optical chirality and provides quantitative insights into the intrinsic optical properties of chiral perovskites for chiroptical and spintronic applications.

Excess iron accumulation mediated senescence in diabetic kidney injury.

Cellular senescence and iron accumulation were separately observed in diabetic nephropathy (DN). Limited evidence supports that iron was significantly accumulated in senescent cells. We aimed to explore whether iron is involved in the pathogenesis role of senescence in DN. Renal cells were treated with high glucose (HG, 35 mM) for 10 or 15 days, and DN mice were induced by high-fat diet and streptozotocin. Gene ontology enrichment, gene set enrichment analysis analysis, ß-galactosidase staining, 5-ethynyl-2-deoxyuridine staining, and western blot depicted the upregulated senescence pathway in vitro and in vivo of DN. Lactate dehydrogenase (LDH) release was increased by HG and reversed by p16/p21 knockdown, and the supernatant of HG-treated cells caused increased LDH release from normal cells. Iron metabolism-related protein expression was disordered after HG exposure concomitant with senescence. Ferric ammonium citrate (50 µM) upregulated gamma-H2A.X variant histone and increased the senescence markers in HG-treated cells. The treatment of deferoxamine (0.5 µM) had the opposite effect. Compared to the non-DN individual, increased ferritin and senescence markers were verified in DN mice and patients, and the co-localization of ferritin and senescence markers was observed by immunofluorescence. These results suggested that accumulated iron was correlated with aggravated DNA damage and accelerated senescence, and revealed the role of iron in the cellular senescence of diseases.

Stigma and self-esteem in facial burn patients: A correlation study.

BACKGROUND: A considerable number of burn patients have greater psychological stress due to the special trauma site. In clinical practice, it is found that medical staff pay more attention to the rehabilitation of physical function, while the mental health status of patients is greatly neglected. In contact with patients, we found that attention should be paid to the levels of stigma and self-esteem. However, there are few studies on stigma and self-esteem in patients with facial burns. Therefore, this study aimed to describe the stigma and self-esteem levels of facial burns, investigate the relationship between these two variables, and explore the influencing factors of stigma in patients with facial burns, in order to provide evidence for follow-up interventions to improve this population. METHODS: From August 2020 to June 2021, we recruited patients with facial burns who met the inclusion criteria in one burn specialist clinic and three burn units of a tertiary A hospital in Guangzhou, China. The survey tools of this study include sociodemographic and disease-related information questionnaires, the Chinese version of the Social Impact Scale, and the self-esteem scale (these scales were validated). SPSS 25.0 software was used for data analysis through t test, analysis of variance, correlation analysis, multiple linear regression method for data statistics. RESULTS: The total stigma score of facial burn patients was (58.01 ± 7.57), which was at a medium level; the self-esteem score was (19.72 ± 2.43), which was at a low level. Correlation analysis showed that there was a positive correlation between the self-esteem score and the total score of stigma (r = 0.286, P < 0.01). The family per capita monthly income, education level, way of medical expenses expenditure, and self-esteem of facial burn patients were the influencing factors of their stigma, and these factors explained 33.7% of the variation in stigma (F=8.659, P＜0.01). CONCLUSIONS: Patients with facial burns have low levels of stigma and self-esteem, which requires our efforts. In particular, there is a positive correlation between stigma and self-esteem, and self-esteem is an independent risk factor affecting stigma. Our findings suggest that interventions aimed at enhancing self-esteem have the potential to positively impact the reduction of stigma in this patient population.

Dataset on the effects of psychological care on depression and suicide ideation in underrepresented children.

Massive increases in the risks of depressive disorders and the ensuing suicide have become the overarching menace for children/adolescents. Despite global consensus to instigate psychological healthcare policy for these children/adolescents, their effects remain largely unclear neither from a small amount of official data nor from small-scale scientific studies. More importantly, in underprivileged children/adolescents in lower-middle-economic-status countries/areas, the data collection may not be as equally accessible as in developed countries/areas, thus resulting in underrepresented observations. To address these challenges, we released a large-scale and multi-center cohort dataset (n = 249,772) showing the effects of primary psychological healthcare on decreasing depression and suicidal ideation in these children/adolescents who were underrepresented in previous studies or current healthcare systems, including unattended children/adolescents, orphans, children/adolescents in especially difficult circumstances, and "left-behind" and "single-parenting" children/adolescents. We provided all individual data recording the depressive symptoms and suicide ideation that had been collected at baseline (Oct 2022) and half-year follow-up (May 2023) from practicing this psychological healthcare system.

Stretchable and Sweat-Wicking Patch for Skin-Attached Colorimetric Analysis of Sweat Biomarkers.

Stretchable sweat sensors are promising technology that can acquire biomolecular insights for health and fitness monitoring by intimate integration with the body. However, current sensors often require microfabricated microfluidic channels to control sweat flow during lab-on-body analysis, which makes effective and affordable sweat sampling a significant practical challenge. Here, we present stretchable and sweat-wicking patches that utilize bioinspired smart wettable membranes for the on-demand manipulation of sweat flow. In a scalable process, the membrane is created by stacking hydrophobic elastomer nanofibers onto soft microfoams with predefined two-dimensional superhydrophobic and superhydrophilic patterns. The engineered heterogeneous wettability distribution allows these porous membranes to achieve enhanced extraction and selective collection of sweat in embedded assays. Despite the simplified architecture, the color reactions between sweat and chemical indicators are inhibited from directly contacting the skin to achieve a largely improved operation safety. The sensing patches can simultaneously quantify pH, urea, and calcium in sweat through digital colorimetric analysis with smartphone images. The construction with all compliant materials renders these patches soft and stretchy to achieve conformal attachment to the skin. Successfully analyzing sweat compositions after physical exercises illustrates the practical suitability of these skin-attachable sensors for health tracking and point-of-care diagnosis.