Metagenomic perspectives on antibiotic resistance genes in tap water: The environmental characteristic, potential mobility and health threat.

As an emerging environmental contaminant, antibiotic resistance genes (ARGs) in tap water have attracted great attention. Although studies have provided ARG profiles in tap water, research on their abundance levels, composition characteristics, and potential threat is still insufficient. Here, 9 household tap water samples were collected from the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) in China. Additionally, 75 sets of environmental sample data (9 types) were downloaded from the public database. Metagenomics was then performed to explore the differences in the abundance and composition of ARGs. 221 ARG subtypes consisting of 17 types were detected in tap water. Although the ARG abundance in tap water was not significantly different from that found in drinking water plants and reservoirs, their composition varied. In tap water samples, the three most abundant classes of resistance genes were multidrug, fosfomycin and MLS (macrolide-lincosamide-streptogramin) ARGs, and their corresponding subtypes ompR, fosX and macB were also the most abundant ARG subtypes. Regarding the potential mobility, vanS had the highest abundance on plasmids and viruses, but the absence of key genes rendered resistance to vancomycin ineffective. Generally, the majority of ARGs present in tap water were those that have not been assessed and are currently not listed as high-threat level ARG families based on the World Health Organization Guideline. Although the current potential threat to human health posed by ARGs in tap water is limited, with persistent transfer and accumulation, especially in pathogens, the potential danger to human health posed by ARGs should not be ignored.

Histone modifications and Sp1 promote GPR160 expression in bone cancer pain within rodent models.

Bone cancer pain (BCP) affects ~70% of patients in advanced stages, primarily due to bone metastasis, presenting a substantial therapeutic challenge. Here, we profile orphan G protein-coupled receptors in the dorsal root ganglia (DRG) following tumor infiltration, and observe a notable increase in GPR160 expression. Elevated Gpr160 mRNA and protein levels persist from postoperative day 6 for over 18 days in the affected DRG, predominantly in small-diameter C-fiber type neurons specific to the tibia. Targeted interventions, including DRG microinjection of siRNA or AAV delivery, mitigate mechanical allodynia, cold, and heat hyperalgesia induced by the tumor. Tumor infiltration increases DRG neuron excitability in wild-type mice, but not in Gpr160 gene knockout mice. Tumor infiltration results in reduced H3K27me3 and increased H3K27ac modifications, enhanced binding of the transcription activator Sp1 to the Gpr160 gene promoter region, and induction of GPR160 expression. Modulating histone-modifying enzymes effectively alleviated pain behavior. Our study delineates a novel mechanism wherein elevated Sp1 levels facilitate Gpr160 gene transcription in nociceptive DRG neurons during BCP in rodents.

A Multi-Channel Urine Sensing Detection System Based on Creatinine, Uric Acid, and pH.

Urine analysis represents a crucial diagnostic technique employed in clinical laboratories. Creatinine and uric acid in urine are essential biomarkers in the human body and are widely utilized in clinical analysis. Research has demonstrated a correlation between the normal physiological concentrations of creatinine and uric acid in urine and an increased risk of hypertension, cardiovascular diseases, and kidney disease. Furthermore, the pH of urine indicates the body's metabolic processes and homeostatic balance. In this study, an integrated multi-channel electrochemical sensing system was developed, combining electrochemical analysis techniques, microelectronic design, and nanomaterials. The architecture of an intelligent medical detection system and the production of an interactive interface for smartphones were accomplished. Initially, multi-channel selective electrodes were designed for creatinine, uric acid, and pH detection. The detection range was 10 nM to 100 µM for creatinine, 100 µM to 500 µM for uric acid, and 4 to 9 for pH. Furthermore, interference experiments were also conducted to verify the specificity of the sensors. Subsequently, multi-channel double-sided sensing electrodes and function-integrated hardware were designed, with the standard equations of target analytes stored in the system's read-only memory. Moreover, a WeChat mini-program platform was developed for smartphone interaction, enabling off-body detection and real-time display of target analytes through smartphones. Finally, the aforementioned electrochemical detection electrodes were integrated with the smart sensing system and wirelessly interfaced with smartphones, allowing for intelligent real-time detection in primary healthcare and individual household settings.

The relationship between self-efficacy, health literacy, and quality of life in patients with chronic diseases: a cross-sectional study in China.

Background: Self-efficacy and health literacy are closely related to the quality of life in patients with chronic diseases; however, it remains unclear whether their combined effects on the quality of life (QoL) in these patients operate through mediation, interaction, or a combination of both. Methods: The research occurred in China between July 10 and September 15, 2021. A multi-stage random sampling technique was utilized to gather information on self-efficacy, health literacy, and QoL among individuals with chronic diseases. Linear regression models investigated the relationships between these patients' self-efficacy, health literacy, and QoL. Additionally, the four-way decomposition method was used to decompose the overall effects of self-efficacy and health literacy on the QoL in patients with chronic diseases. Results: Significant correlations were found between self-efficacy, health literacy, and QoL among individuals with chronic diseases (all p < 0.05). In the four-way decomposition results, the results of the European Quality of Life Five Dimension Five Level (EQ-5D-5L) displayed the interaction effects mediated by self-efficacy, and the reference interaction effects were not significant, with small effect sizes observed. The influence of health literacy levels on the QoL in these patients was primarily attributed to the controlled direct effect (CDE), accounting for approximately 86.12% [excess relative risk = 0.00415; 95% CI: 0.00326, 0.00504; p < 0.0001]. The proportion solely attributable to the pure indirect effect (PIE) of self-efficacy was 14.5% [excess relative risk = 0.0007; 95% CI: 0.00031, 0.00109; p < 0.0001]. In the EQ visual analog scale (EQ-VAS) results, the proportion of the controlled direct effect was 84.9% [excess relative risk = 0.62443; 95% CI: 0.52269, 0.72618; p < 0.0001], while the proportion solely attributable to the pure indirect effect of mediation was 14.8% [excess relative risk = 0.10876; 95% CI: 0.06409, 0.15344; p < 0.0001]. Conclusion: Self-efficacy and health literacy primarily influence QoL in patients with chronic diseases through controlled and pure indirect effects. Enhancing patients' health literacy and self-efficacy can contribute to improving their QoL.

A highly elastic, moisturizing, and adhesion conductive hydrogel designed for cuffless blood pressure measurement.

Real-time monitoring of blood pressure in athletes during exercise is of great importance, however, conventional methods pose challenges in achieving portable and instantaneous measurements. While, the electrodes used in emerging wearable blood pressure monitoring instruments still have certain defects. In this study, a novel cuffless blood pressure monitoring system was developed using a self-developed polyacrylamide/trehalose/LiCl (PAM/Trehalose/LiCl) conductive hydrogel as the electrode material. The hydrogel electrode has high tensile (strain: 3568 %) and conductive properties (7.57 S/m), while also exhibiting low toughness, moisture retention, and adhesion. While ensuring the comfort of the monitoring system, it can also accurately detect strain over a wide range of deformations (GF value of up to 6.31 in the strain interval of 2000-3400 %). Finally, this system accurately extracts relevant features of PPG and ECG signals and predicts cuff-less blood pressure using the BP Transformer-XL model. The main control chip, ECG detection module, Bluetooth module, and PPG detection module are integrated, and band-pass filtering and data feature extraction techniques are combined. The study found that the average errors in systolic and diastolic readings were 2.09 mmHg and 1.57 mmHg, respectively, compared to those measured by an electronic sphygmomanometer. Therefore, this study successfully combined hydrogel electrodes with a cuffless blood pressure monitoring system to provide technical support for the development of personalized training programs for future athletes and the guarantee of long-term competitive performance.

A Numerical Study of the Mechanical Behavior of Jointed Soft Rocks under Triaxial Loading Using a Bonded Particle Model.

In order to master the strength and deformation characteristics, including the macro-micro failure mechanism of soft rock samples with penetrating joints under triaxial loading, a series of numerical triaxial tests have been carried out. The strength and deformation characteristics, failure modes, crack propagation, distribution of force chains, and the influences of joint dip angles and confining pressures have been analyzed and compared with the laboratory test results. The results show that (1) the residual strength ratio of jointed rock samples generally increases first and then decreases with the increase in joint dip angles under the same confining pressure and reaches the maximum value around 23-24°. Poisson's ratio increases with the increase in the confining pressure or the joint dip angle. The elastic modulus increases with the increase in the confining pressure and decreases with the increase in the joint dip angle. (2) The jointed rock samples with different joint dip angles compact with relatively small volumetric strains and then dilate up to failure with relatively large volume expansions. Lower confining pressure and smaller dip angles will lead to a more pronounced dilation phenomenon and less obvious volume shrinkage rules. (3) The low-angle jointed rock samples all exhibit the X-type shear failure. The jointed rock samples with a joint dip angle of 45° exhibit hybrid failure with both slippage and shearing, which are controlled by both the matrix and the joint. (4) The change in the number of cracks includes three stages: the slow crack initiation stage, rapid growth stage, and crack coalescence stage. The total number of shear or tensile cracks all decrease with an increase in the joint dip angles, with the number of tensile cracks being approximately twice that of shear cracks. The tension cracks are mostly horizontal, and the shear cracks are mostly vertical. (5) The number of force chains shows a decreasing trend after the cracks begin to grow. The jointed rock samples for the intact, 15° and 30° cases all form a main force chain during the failure process, while there is no main force chain for the 45° case.

The congruence between the preferred and actual places of death among terminal cancer patients in China.

Background: Dying in a preferred place is important for a good death. Currently, no study has evaluated the extent to which the preferences for the place of death (PoD) are met among terminal cancer patients in China. This study examined the congruence between the preferred and actual PoD and its predictors among terminal cancer patients in China. Methods: Between 2015 and 2023, 845 terminal cancer patients from four tertiary hospitals in Wuhan, China, were enrolled and followed till death. Face-to-face surveys at baseline and telephone-based interviews in the last month of patients' lives were combined to learn patients' preferred PoD. Data on patients' actual PoD were collected from families within 1 month after patients' death. Results: Of the 410 patients who died, 62.7% of them died in hospitals. The agreement between patients' preferred and actual PoD was fair (κ = 0.221). The congruence between patients' preferred and actual PoD was 63.0, 36.6%, and 0 for hospital death, home death, and hospice facility/nursing home death separately. Patients were more likely to die in their preferred places if their preferred place and family caregivers' belief of patients' preferred PoD was congruent (odds ratio [OR] = 6.464, p = 0.001), or if caregivers had a medically related occupation (OR = 4.577, p = 0.003); if patients were hospitalized at least twice in the last month of life (OR = 0.422, p = 0.000), or the quality of care received by patients in the last 48 h was rated good by the families (OR = 0.373, p = 0.011), patients were less likely to die in their preferred places. Conclusion: The congruence between patients' preferred and actual PoD was fair. Advance care planning (ACP) needs to be popularized in China, and the quality of care in hospice facilities and nursing homes should be improved. The necessary policy support for hospice care should be made to respect cancer patients' end-of-life (EoL) care preferences in China.

An intelligent fluorescence sensing platform based on entropy-driven toehold-mediated strand displacement cycle reaction for point-of-care testing of miRNA.

BACKGROUND: MicroRNA (miRNA) has gradually become an emerging biomarker for early diagnosis and prognosis of various diseases due to its specific gene expression and high stability. With the development of molecular diagnosis and point-of-care testing (POCT) technology, developing simple, fast, sensitive, efficient, and low-cost miRNA sensors is of great significance for clinical applications and emergency rapid diagnosis. At present, entropy-driven toehold mediated chain displacement reaction, as a promising enzyme free isothermal amplification technique, is an important tool for ultra-sensitive biosensing applications. RESULTS: In this study, we used gold nanoparticles (AuNPs) as carriers and quenchers, modified them using self-assembled triple chain composite substrates AuNPs@A@B1/B2, and used dual reporter molecules for cascade cyclic amplification to amplify fluorescence signals, which proposed a fluorescent biosensor based on this reaction and build an intelligent fluorescence sensing platform for rapid detection of miRNA. We designed a highly specific self-programmable sensor using the acute ischemic stroke (AIS) biomarker miRNA-125a-5p as a sample, and achieved sensitive detection of miRNA in the range of 0.01 µM∼10 µ M under optimal conditions. It broke through the traditional detection limitations of weak signals and liberated the fluorescence detection environment. SIGNIFICANCE: In summary, this creative miRNA biosensor combined with POCT has demonstrated extraordinary detection potential, broad application prospects in the early diagnosis and prognosis monitoring of AIS, provides a novel miRNA universal detection strategy for the fields of biological and life sciences.

Mutating a flexible region of the RSV F protein can stabilize the prefusion conformation.

The respiratory syncytial virus (RSV) fusion (F) glycoprotein is highly immunogenic in its prefusion (pre-F) conformation. However, the protein is unstable, and its conformation must be stabilized for it to function effectively as an immunogen in vaccines. We present a mutagenesis strategy to arrest the RSV F protein in its pre-F state by blocking localized changes in protein structure that accompany large-scale conformational rearrangements. We generated a series of mutants and screened them in vitro to assess their potential for forming a stable pre-F. In animals, the immunogenicity of a representative mutant F protein, with a conformation confirmed by cryo-electron microscopy, elicited levels of neutralizing antibodies and protection against RSV-induced lung damage that were comparable to those of DS-Cav1, a pre-F used in a licensed vaccine.

The clinical value of ultrasound-guided sacral anesthesia in Intracavitary and/or interstitial brachytherapy for cervical Cancer.

OBJECTIVE: To explore the effectiveness and safety of ultrasound-guided sacral anesthesia in intracavitary and/or interstitial brachytherapy for cervical cancer patients. METHOD: A retrospective analysis was conducted on a total of 1039 intracavitary and/or interstitial brachytherapy involving 220 patients in our department from December 7, 2020 to March 21, 2024. The study assessed the satisfaction with anesthesia, changes in vital signs, onset time of anesthesia, dosage of anesthetic drugs, duration of anesthesia, and incidence of adverse reactions. RESULT: The rate of satisfaction with anesthesia was 73.8 %. There were no significant differences in patients' heart rate (HR), mean arterial pressure (MAP), systolic blood pressure (SBP), or oxygen saturation (SaO2) before and after anesthesia (P > 0.05). The onset time of anesthesia ranged from 20 to 35 min, the average dosage of anesthetic was 20 ml, and the duration of anesthesia lasted from 30 to 120 min. Serious adverse reactions included 2 cases of post-anesthesia syncope (associated with sacral cysts). The incidence of nausea was 2.2 %, and the total incidence of other adverse reactions, such as vomiting, urinary retention, bradycardia, anal discomfort, and dizziness, was less than 1 %. CONCLUSION: Ultrasound guided sacral anesthesia demonstrates significant advantages, including effective anesthesia, minimal impact on vital signs, rapid onset, prolonged maintenance, and a low incidence of adverse reactions. It is recommended for widespread application in intracavitary and/or interstitial brachytherapy for cervical cancer patients.

Recovery From Severe Mental Illnesses: The Influence of Personal and Psychosocial Factors in Community Settings.

Severe mental illnesses (SMIs) represent a significant public health challenge with substantial personal, economic and societal burdens. Despite treatment advances, recovery outcomes for SMI patients remain variable. This study aimed to investigate the influence of personal and psychosocial factors on recovery among SMI patients in community health settings. This cross-sectional study was conducted in 23 community health service centres in Nanjing, China. We recruited 924 participants diagnosed with SMIs, using a random sampling method. The relationships between individual, psychosocial factors and patients' recovery status were analysed by multiple linear regression. The mediation effect of medication adherence was further tested by the Sobel test with bootstrapping. The mean score of the Morningside Rehabilitation Status Scale (MRSS) of 924 patients with SMIs was 49.82 ± 41.52. The main influencing personal factors of recovery status were age, marital status, education, average annual income and duration of illness. Patients who were accepted by their families tended to have better recovery outcomes, while stigma and social impairment may hinder recovery. Medication adherence played a mediating role between psychosocial factors and recovery status. This study highlights the crucial role of psychosocial factors in the treatment and recovery of SMI patients. Furthermore, medication adherence emerged as a mediating factor. Implementing targeted interventions and policies addressing identified psychosocial barriers can offer promising avenues for improving recovery outcomes for SMI patients in community settings.

Comprehensive analysis of benzothiazoles (BTHs), benzotriazoles (BTRs), and benzotriazole ultraviolet absorbers (BUVs) in the western South China Sea: Spatial distributions, migration tendencies and ecotoxicological relevance.

Benzothiazoles (BTHs), benzotriazoles (BTRs), and benzotriazole ultraviolet absorbers (BUVs) have garnered significant attention owing to their persistent nature in the environment and adverse impacts on aquatic organisms. However, there remains a dearth of investigations and studies conducted in tropical marine environments. In this study, we undertook the inaugural distributional survey and ecotoxicological relevance of BTHs, BTRs, and BUVs in seawater and sediments of the western South China Sea (WSCS). Elevated concentrations of BTHs, BTRs, and BUVs in the seawater and suspended particulate matter (SPM) were primarily observed in the Pearl River Estuary (PRE) and the western region of the WSCS, attributed to terrestrial runoff and hydrodynamic processes. Moreover, the transport of these compounds at the seawater-SPM interface was influenced by both the intrinsic properties of the contaminants and temperature variations. Spatially, concentrations of BTHs, BTRs, and BUVs in surface sediments exhibited a diminishing trend with increasing distance from the coast to offshore areas, reflecting notable anthropogenic impacts. Concentration profiles of these compounds in sediment cores displayed a bottom-up increasing trend, with total organic carbon (TOC) identified as the primary determinant governing their accumulation within sediment cores in the WSCS. Terrestrial runoff inputs and atmospheric deposition as major contributors to the occurrence of BTHs, BTRs, and BUVs in the WSCS. Simultaneously, the study underscores the non-negligible moderate mixture risk quotient associated with BTHs, BTRs, and BUVs in the sediments.

A Nomogram of Predicting Healthcare-Associated Infections in Burned Children.

BACKGROUND: Healthcare-associated infections (HAIs) are a common clinical concern associated with adverse prognosis and mortality in burned children. This study aimed to construct a predictive nomogram of the risk of HAIs in burned children. METHODS: Children admitted to the burn unit of Wuhan Third Hospital between 2020 and 2022 were included. The univariate and multivariate logistic regression analyses were adopted to ascertain predictors of HAIs. A nomogram was developed to predict the HAI risk of each patient, with receiver operating characteristic curves and calibration curves being generated to assess its predictive ability. Furthermore, decision and impact curves were used to assess the clinical utility. RESULTS: Of 1122 burned children, 61 (5.5%) patients experienced HAIs. The multivariate analysis indicated that total burn surface area, length of stay, surgery, central venous catheter use and urinary catheter use were the independent risk factors of HAIs. Using these variables, we developed a predictive nomogram of the occurrence of HAIs in burned children, and the internal validation results demonstrated good discrimination and calibration of the nomogram. The area under the curve values of the nomogram was 0.926 (95% CI, 0.896-0.957). The calibration curve showed high consistency between the actual and predicted HAIs. The decision and impact curve indicated that the nomogram was of good clinical utility and more credible net clinical benefits in predicting HAIs. CONCLUSIONS: The present study constructed a nomogram for predicting the risk of HAIs in burned children. This nomogram may strengthen the effective screening of patients at high risk of HAIs.

A predictive model for L-T4 dose in postoperative DTC after RAI therapy and its clinical validation in two institutions.

Purpose: To develop a predictive model using machine learning for levothyroxine (L-T4) dose selection in patients with differentiated thyroid cancer (DTC) after resection and radioactive iodine (RAI) therapy and to prospectively validate the accuracy of the model in two institutions. Methods: A total of 266 DTC patients who received RAI therapy after thyroidectomy and achieved target thyroid stimulating hormone (TSH) level were included in this retrospective study. Sixteen clinical and biochemical characteristics that could potentially influence the L-T4 dose were collected; Significant features correlated with L-T4 dose were selected using machine learning random forest method, and a total of eight regression models were established to assess their performance in prediction of L-T4 dose after RAI therapy; The optimal model was validated through a two-center prospective study (n=263). Results: Six significant clinical and biochemical features were selected, including body surface area (BSA), weight, hemoglobin (HB), height, body mass index (BMI), and age. Cross-validation showed that the support vector regression (SVR) model was with the highest accuracy (53.4%) for prediction of L-T4 dose among the established eight models. In the two-center prospective validation study, a total of 263 patients were included. The TSH targeting rate based on constructed SVR model were dramatically higher than that based on empirical administration (Rate 1 (first rate): 52.09% (137/263) vs 10.53% (28/266); Rate 2 (cumulative rate): 85.55% (225/263) vs 53.38% (142/266)). Furthermore, the model significantly shortens the time (days) to achieve target TSH level (62.61 ± 58.78 vs 115.50 ± 71.40). Conclusions: The constructed SVR model can effectively predict the L-T4 dose for postoperative DTC after RAI therapy, thus shortening the time to achieve TSH target level and improving the quality of life for DTC patients.

Petroleum hydrocarbons and colored dissolved organic matter shape marine oil-degrading microbiota in different patterns.

Both petroleum hydrocarbons (PHCs) from oil pollution and colored dissolved organic matter (CDOM) have great influences on the marine microbial community as carbon source factors. However, their combined effects and the specific influence patterns have been kept unclear. This study selected the northeastern South China Sea (NSCS), a typical oil contaminated area, and investigated the characteristics of oil-degrading microbiota in the seawaters by high-throughput sequencing and the relationships with PHCs and CDOM as well as other environmental factors. The results showed the oil pollution had induced the enrichment of oil-degrading bacteria and oil-degrading functional genes, resulting in the core function of oil-degrading microbiota for shaping the microbial community. The Mantel test indicated carbon source factors played the dominant role in shaping the oil-degrading microbiota, compared with geographical distance and other non­carbon source factors. The influence patterns and strength of PHCs and CDOM on oil-degrading microbiota were further comprehensively analyzed. PHCs played a driving role in the differentiation of oil-degrading microbiota, while CDOM played a stabilizing role for the community similarity. The constructed structural equation model confirmed their distinct influence patterns and also explored the mediating effects of bulk organic carbon. This work not only revealed the important impact of oil pollution on marine microbial communities, but also made people realize the self-regulation ability of the marine environment through the endogenous organic matter.

Monocyte-to-Albumin Ratio Is Associated With Hematoma Expansion in Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Hematoma expansion (HE) after spontaneous intracerebral hemorrhage (ICH) is a severe complication that independently predicts poor prognosis. In this study, we aimed to investigate whether monocyte-to-albumin ratio (MAR), a novel marker of systemic inflammation, could predict HE in patients with ICH. METHODS: We retrospectively assessed the data of patients with ICH. The clinical, imaging, and laboratory test data including, the MAR on admission, were analyzed. A multivariate logistic regression analysis was carried out to explore the relationship between MAR and hematoma growth. The receiver operating characteristic (ROC) curve was employed to investigate the predictive value of MAR for HE after ICH. RESULTS: A total of 246 patients were included in the present study. Multivariate logistic regression analysis demonstrated that the MAR was associated with HE (odds ratio [OR] = 1.179; 95% confidence interval, 1.093-1.272; p = 0.000). ROC curve analysis showed that MAR could predict HE, with an area under the curve of 0.802 (95% CI: 0.744-0.859, p < 0.001). The optimal predictive cutoff value of MAR for HE was 10.01 (sensitivity: 72.43%, specificity: 77.05%). CONCLUSIONS: Our results suggested that a high MAR on admission was associated with an increased risk of HE in ICH patients, and MAR can become an independent predictor of HE in ICH patients.

Graphene Oxide/Black Phosphorus Functionalized Collagen Scaffolds with Enhanced Near-Infrared Controlled In Situ Biomineralization for Promoting Infectious Bone Defect Repair through PI3K/Akt Pathway.

Infectious bone defects resulting from surgery, infection, or trauma are a prevalent clinical issue. Current treatments commonly used include systemic antibiotics and autografts or allografts. Nevertheless, therapies come with various disadvantages, including multidrug-resistant bacteria, complications arising from the donor site, and immune rejection, which makes artificial implants desirable. However, artificial implants can fail due to bacterial infections and inadequate bone fusion after implantation. Thus, the development of multifunctional bone substitutes that are biocompatible, antibacterial, osteoconductive, and osteoinductive would be of great clinical importance. This study designs and prepares 2D graphene oxide (GO) and black phosphorus (BP) reinforced porous collagen (Col) scaffolds as a viable strategy for treating infectious bone defects. The fabricated Col-GO@BP scaffold exhibited an efficient photothermal antibacterial effect under near-infrared (NIR) irradiation. A further benefit of the NIR-controlled degradation of BP was to promote biomineralization by phosphorus-driven and calcium-extracted phosphorus in situ. The abundant functional groups in GO could synergistically capture the ions and enhance the in situ biomineralization. The Col-GO@BP scaffold facilitated osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSC) by leveraging its mild photothermal effect and biomineralization process, which upregulated heat shock proteins (HSPs) and activated PI3K/Akt pathways. Additionally, systematic in vivo experiments demonstrated that the Col-GO@BP scaffold obviously promotes infectious bone repair through admirable photothermal antibacterial performance and enhanced vascularization. As a result of this study, we provide new insights into the photothermal activity of GO@BP nanosheets, their degradation, and a new biological application for them.

A survival nomogram involving nutritional-inflammatory indicators for cervical cancer patients receiving adjuvant radiotherapy.

Objective: The combined impact of nutritional and inflammatory status on survival of cervical cancer patients remained unclear. This study aimed to construct a survival nomogram involving both nutritional and inflammatory indicators and evaluate their potential correlation. Methods: This retrospective study included 325 cervical cancer patients who received adjuvant radiotherapy between September 2010 and September 2020. Baseline nutritional indicators such as body mass index (BMI), controlling nutritional status (CONUT) and serum albumin were assessed. Inflammatory indicators of platelet/lymphocyte ratio (PLR), neutrophil/lymphocyte ratio (NLR), systemic immune inflammation index (SII) and system inflammation response index (SIRI) were evaluated respectively. The LASSO regression and Cox regression models were applied for variable selection and nomogram building. The predictive accuracy and superiority of prognostic model were assessed by area under curve (AUC), C-index, decision curve analysis (DCA), integrated discrimination improvement (IDI) and net reclassification improvement (NRI). Results: Patients with high inflammatory indicators (PLR, NLR and SII) and poor nutritional status (CONUT scores > 2) suffered poorer prognosis compared to these with well nutritional status and lower inflammation levels. Our study unveiled a positive correlation between malnutrition and hyperinflammation. Even after accounting for baseline inflammatory level, malnutrition remained a significant risk factor for patients. Notably, the inflammatory level and nutritional status were further modulated by the clinical features of patients. Patients with poorer nutritional status exhibited higher levels of PLR, NLR, SII and SIRI, particularly for those in advanced clinical stages and with non-squamous cell carcinoma. In addition, our study found elevated levels of circulating basophil and serum carbohydrate antigen 125 (CA125) were associated with the poor prognosis. The prognostic nomogram which incorporated the nutritional-inflammatory indicators of PLR and CONUT showed a favorable performance with the AUC value of 0.76 at 5-year survival prediction. The DCA, IDI and NRI consistently demonstrated the favorable superiority of the model. Moreover, the nomogram-based risk stratification system could effectively classify patients into three mortality risks subgroups. Conclusions: Poorer nutritional and high inflammatory status collectively contributed to the poorer prognosis. The prognostic nomogram which incorporated nutritional-inflammatory indicators significantly improved the prediction of long-term outcomes of cervical cancer patients undergoing adjuvant radiotherapy.

Catalytic divergence of O-methyltransferases shapes the chemo-diversity of polymethoxylated bibenzyls in Dendrobium catenatum.

Erianin, crepidatin, and chrysotobibenzyl are typical medicinal polymethoxylated bibenzyls (PMBs) that are commercially produced in Dendrobium species. PMBs' chemo-diversity is mediated by the manifold combinations of O-methylation and hydroxylation in a definite order, which remains unsolved. To unequivocally elucidate the methylation mechanism of PMBs, 15 possible intermediates in the biosynthetic pathway of PMBs were chemically synthesized. DcOMT1-5 were highly expressed in tissues where PMBs were biosynthesized, and their expression patterns were well-correlated with the accumulation profiles of PMBs. Moreover, cell-free orthogonal tests based on the synthesized intermediates further confirmed that DcOMT1-5 exhibited distinct substrate preferences and displayed hydroxyl-group regiospecificity during the sequential methylation process. The stepwise methylation of PMBs was discovered from SAM to dihydro-piceatannol (P) in the following order: P → 3-MeP → 4-OH-3-MeP → 4-OH-3,5-diMeP → 3,3'(4'),5-triMeP → 3,4,4',5-tetraMeP (erianin) or 3,3',4,5-tetraMeP (crepidatin) → 3,3',4,4',5-pentaMeP (chrysotobibenzyl). Furthermore, the regioselectivities of DcOMTs were investigated by ligand docking analyses which corresponded precisely with the catalytic activities. In summary, the findings shed light on the sequential catalytic mechanisms of PMB biosynthesis and provide a comprehensive PMB biosynthetic network in D. catenatum. The knowledge gained from this study may also contribute to the development of plant-based medicinal applications and the production of high-value PMBs.

Identification and characterization of new Siberian subtype of tick-borne encephalitis virus isolates revealed genetic variations of the Chinese strains.

Tick-borne encephalitis virus (TBEV) is a pathogen that causes febrile infectious diseases and neurological damage to humans. TBEVs are prevalent from Europe to Far Eastern Asia, including Northeastern China. The understanding of TBEV phylogeny in China has been limited owing to insufficient genomic data on Chinese TBEV strains. Here, six TBEV strains were isolated from ticks collected in Inner Mongolia. The transmission electron microscopy revealed spherical particles with an enveloped structure of 50-60 nm in diameter. Phylogenetic analysis showed that, two strains were classified as the Siberian subtype, while the remaining four were identified as the Far Eastern subtype. Migration analyses based on TBEV ORF and envelope (E) protein sequences revealed that Chinese TBEV strains were migrated from Russia and/or Kazakhstan into China. Hulun Buir and Mudanjiang, the northeastern region of China, are considered hotspots with multiple import and export routes of Chinese TBEV strains. These results promote the understanding of TBEV genetic variations and phylogeny in China and suggest the importance of improving investigation of TBEV prevalence, which would instrumental for vaccine design strategies and better preparation for controlling TBEV infection in humans.