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Abstract Background Achieving complete immune reconstitution (CIR) in people living with human immunodeficiency virus (PLWH) following antiretroviral therapy (ART) is essential for preventing acquired immunodeficiency syndrome (AIDS) progression and improving survival. However, there is a paucity of robust prediction models for determining the likelihood of CIR in PLWH after ART. We aimed to develop and validate a CIR prediction model utilizing baseline data. Methods Baseline data including demographic information, immunological profiles, and routine laboratory test results, were collected from PLWH in Yunnan, China. Baseline referred to the first recorded results after HIV diagnosis but before initiating ART, and these initial measurements served as the baseline data for analysis. The participants were divided into training and validation sets (7:3 ratio). To construct the model and accompanying nomogram, univariable and multivariable Cox regression analyses were performed. The model was evaluated using the C-index, time-dependent receiver operating characteristic (ROC) curves, calibration curves, and clinical decision curves to assess discrimination, calibration, and clinical applicability. Results Five thousand four hundred eight PLWH were included, with a CIR of 38.52%. Cox regression analysis revealed various independent factors associated with CIR, including infection route, baseline CD4+T cell count, baseline CD4/CD8 ratio, interval from HIV diagnosis to ART initiation, and the level of PLT, Glu, Crea, HGB, ALT. A nomogram was formulated to predict the probability of achieving CIR at years 4, 5, and 6. The model demonstrated good performance, as evidenced by an AUC of 0.8 for both sets. Calibration curve analysis demonstrated a high level of agreement, and decision curve analysis revealed a significant positive yield. Conclusions This study successfully developed a prediction model with robust performance. This model has considerable potential to aid clinicians in tailoring treatment strategies, which could enhance outcomes and quality of life for PLWH.

Abstract Breast cancer (BC) is a significant cause of cancer-related deaths among women worldwide. Hypoxia, a common feature of solid tumor, is associated with drug resistance and a poor prognosis in BC. In this study, we present a strategy to overcome hypoxia-induced chemotherapy tolerance in BC. Specifically, we synthesized a hollow gold (Au)-platinum (Pt) bimetallic nanoshell for the first time, which acted as a drug delivery system (DDS) for doxorubicin (DOX). The photothermal effect, induced by the surface plasmon resonance (SPR) from the Au-Pt shell under near infrared-II (NIR-II) laser irradiation, not only directly causes tumor cell death through photothermal therapy (PTT), but also significantly enhances the catalase-like activity between Pt nanoparticles and endogenous H2O2. This, subsequently, results in a heightened yield of O2, which further facilitates the release of DOX. This process alleviates tumor hypoxia and down-regulating hypoxia-inducible factor-1α (HIF-1α), multidrug resistance gene 1 (MDR1), and P-glycoprotein (P-gp), which can reverse drug resistance and achieve more effective DOX chemotherapy effects. Significantly, the increased availability of oxygen further re-polarizes immunosuppressive M2 macrophages into antitumor M1 macrophages. This study presents a novel strategy to tackle tumor proliferation and enhance tumor response to chemotherapy, offering hope for reversing in drug resistance in cancerous lesions. Graphical Abstract

Abstract In the modern healthcare system, the rational allocation of emergency department (ED) resources is crucial for enhancing emergency response efficiency, ensuring patient safety, and improving the quality of medical services. This paper focuses on the issue of ED resource allocation and designs a priority sorting system for ED patients. The system classifies patients into two queues: urgent and routine. Considering different service rates, a multi-server preemptive priority queueing model $$(M/M/c_{1}/K)$$ and a multi-server non-preemptive priority queueing model $$(M/M/c_{2}/\infty )$$ are constructed. Additionally, the number of beds, K, is introduced as the capacity of the urgent queue. By comprehensively considering the costs associated with patient waiting time, the cost of rejecting the most critical patients, and the total costs of beds and servers, a mixed-integer programming model was constructed with the objective of minimizing the total cost. The particle swarm optimization algorithm was applied to determine the optimal number of servers, service rate, and number of beds. Compared with the model proposed by Alipour-Vaezi et al., our model significantly improves patient waiting times and queue lengths using the same data set: the waiting time $$W_{q}^{1}$$ decreased by 74.44%, $$W_{q}^{3}$$ by 5.79%, and $$W_{q}^{4}$$ by 1.13%; the queue length $$L_{q}^{1}$$ decreased by 78% and $$L_{q}^{3}$$ by 3.33%. Our model effectively reduces patient waiting times and queue lengths while controlling costs, identifies the optimal number of beds, and achieves optimized resource allocation. Finally, we conducted a sensitivity analysis and provided some valuable management insights.

Abstract Background Older people living with HIV-1 (PLWH) experience a dual burden from the combined effects of aging and HIV-1 infection, resulting in significant immune dysfunction. Despite receiving HAART, immune reconstitution is not fully optimized. The objective of this study was to investigate the impact of aging and HAART on T cell subsets and function in PLWH across different age groups, thereby providing novel insights into the prognosis of older PLWH. Method This study was conducted at Yunnan AIDS Care Center, China, to explore the immunological responses of old PLWH to HAART and compared with the middle-age and the younger. Blood samples were collected from 146 PLWH to analyze T cell subsets and their functions, with a particular emphasis on markers related to T cell differentiation, activation, exhaustion, inflammation, and cellular function, using multicolor flow cytometry analysis. Results Older age may have a greater effect on long-term CD4+T cell recovery. Compared with young and middle-aged PLWH, older PLWH presented distinct alterations in their immune profile, including a decline in the Naïve CD4+T and CD8+T cell subsets, an expansion of effector memory cells, and other potential immune risk phenotypes, such as activation, exhaustion, and up-regulation of aging markers. In addition, we observed a significant association between the CD4 + EM3 subset and the CD8 + EM2 subset with HIV-1 progression, independent of age, suggesting their potential as reliable markers for assessing immune reconstitution in all PLWH. Conclusion Our study extends previous findings showing that older participants exhibit a wide range of late differentiation, senescence, or exhaustion phenotypes in cells, including all the CD4+T and CD8+T subsets, consistent with an immunosenescent phenotype. This may accelerate poor immune recovery in older PLWH. Identifying new strategies to improve the immune risk phenotypes of older PLWH may help improve their immune reconstitution outcomes. The CD4 + EM3 subset and the CD8 + EM2 subset should be studied as additional markers of late presentation.

Abstract Background The best open side for unilateral open-door laminoplasty (UODL) to treat inconsistent cervical ossification of the posterior longitudinal ligament (OPLL) needs to be identified. Methods Thirty-one individuals with inconsistent OPLL who underwent UODL between January 2016 and December 2018 were retrospectively divided into two groups: when the side of the open door was consistent with the side of the larger ossification occupancy area, patients were placed in the Consistent group; when the side of the open door was contralateral to the side of the larger ossification occupancy area, patients were placed in the Contralateral group. The following parameters were evaluated: neck disability index (NDI) score, Japanese Orthopaedic Association (JOA) score, visual analog scale (VAS) score, postoperative laminoplasty opening width and angle, and spinal cord diameter ratio. Spinal cord shifts were also evaluated to compare the clinical results between the two groups. Results Patient demographics and major problems did not differ significantly between the groups. Transient pain in the deltoid region was more frequent in the Consistent treatment group. The spinal cord diameter ratio, VAS and NDI scores, opening width, and angle in postoperative laminoplasty did not differ significantly between the two groups. The JOA scores improved in the Consistent group. The spinal cord diameter ratio and spinal cord shift were more significantly improved in the Consistent group. Conclusions For inconsistent cervical OPLL, the open-door side that was consistent with a larger ossification occupancy area was preferred in UODL.

Abstract Ammonia volatilized from penguin excreta is a significant nitrogen source in Antarctic ecosystems, influencing climate through new particle formation (NPF). Freeze-thaw events can trigger ammonia emissions, but their impact on penguin-derived ammonia is understudied and overlooked in models. Here we investigate the contribution of penguins to ammonia and their climatic impacts using cruise observations and GEOS-Chem-APM simulations. High ammonia concentrations, with a maximum exceeding 7000 ng/m3, were observed over the Southern Ocean and Prydz Bay, driven by air masses from penguin colonies. Simulations showed that incorporating freeze-thaw impact improves model performance, with penguin-derived ammonia emissions enhanced by up to 20-fold and reaching a total of 49 Gg across Antarctica in November. Elevated ammonia increased simulated secondary particle number concentrations by 30−300% through NPF, enhancing simulated cloud droplet number concentrations by 10−20% and altering cloud properties. This study underscores the importance of incorporating penguin emissions into models, particularly during freeze-thaw events.

177Lu- prostate specific membrane antigen (PSMA) radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China. Based on domestic clinical practice and experimental data and referred to international experience and viewpoints, the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Abstract The diverse and dynamic population of microorganisms present in the gut microbiota may affect host health. There are evidences to support the role of gut microbiota as a key player in reproductive development. Unfortunately, the relationship between reproductive disorders caused by aging and gut microbiota remains largely unknown. Here, it is shown for the first time that gut microorganism Bacteroides fragilis (BF) transplantation ameliorates ovarian aging by transporting extracellular vesicles (EVs) through the gut‐ovary axis. Mechanistically, miR‐1246 is enriched in EVs derived from BF‐treated intestinal cells, and these miR‐1246‐enriched EVs are transferred to ovaries, thereby effectively improving reproductive senescence by reducing oxidative stress in the ovaries. Specifically, miR‐1246 reduces the ubiquitination of p62 and stabilizes the protein level of p62 by targeting E3 ligase SKP2. Then Keap1‐Nrf2 complex is dissociated and Keap1 is recruited to form the p62‐Keap1 complex. With the dissociation of Keap1‐Nrf2 complex, Nrf2 is released and activated, thus promoting the transcription of antioxidant enzymes and relieving reproductive senescence. Collectively, the data indicates that intestinal cell‐derived EVs serve as natural information carriers in the crosstalk between the gut and the ovary, and intestinal microorganism transplantation is a promising approach for the treatment of ovarian dysfunction diseases.

Bipolar disorder (BD) is a prevalent mood disorder characterized by alternating episodes of depression and mania, often accompanied by varying degrees of cognitive impairment. Cognitive impairments often serve as indicators of a bleak prognosis or the likelihood of progressing to dementia. Additionally, some studies suggest that individuals diagnosed with BD may undergo a decline in hippocampal volume. However, the potential for reversibility of these changes, particularly in adolescents, remains unclear. We present an intriguing case involving an 18-year-old male student who experiences concurrent occurrences of both BD and mild cognitive impairment (MCI), accompanied by a subtle reduction in hippocampal volume. Initially, the individual exhibited impaired general cognitive function, as indicated by an IQ score of 80 on the Standard Raven’s Progressive Matrices test, and demonstrated slightly reduced bilateral hippocampal volume compared to the normative reference, as determined through quantitative structural magnetic resonance imaging (qsMRI). The deposition profiles of amyloid beta (Aβ) peptide in the brain were not identified with 18F-AV45 PET/MRI. Following six months of combined psychopharmacological treatment and cognitive behavioral therapy, the individual’s psychopathological symptoms improved significantly, leading to a restoration of his IQ score to 116 and normalization of hippocampal volume. This case suggests that the hippocampal volume reduction and cognitive impairment seen in some adolescents with BD may demonstrate greater plasticity compared to neurodegenerative conditions such as Alzheimer’s disease (AD). These findings highlight the potential importance of early intervention in young BD patients with cognitive impairments.

ObjectiveThis study systematically evaluated the efficacy of programmed death 1 (PD-1) inhibitors combined with chemotherapy for advanced esophageal cancer (EC).MethodsPubMed, Embase, Web of Science, Scopus, and Cochrane Library were searched to identify related randomized controlled trials (RCTs).ResultsSeven RCTs involving 4,363 participants were included. The results of the direct comparison showed that, compared with chemotherapy alone, PD-1 inhibitors combined with chemotherapy significantly improved overall survival (OS) (HR = 0.69, 95%CI = 0.63–0.74), progression-free survival (PFS) (HR = 0.63, 95%CI = 0.58–0.67), objective response rate (ORR) (RR = 1.41, 95%CI = 1.28–1.57), but were associated with a slight increase in treatment-related adverse events (AEs) (RR = 1.08, 95%CI = 1.03–1.14). The results of the network meta-analysis showed that toripalimab, sintilimab or camrelizumab, and nivolumab combined with chemotherapy were the best in OS, PFS, and ORR, respectively, with camrelizumab showing the lowest incidence of AEs.ConclusionThese results suggest that PD-1 inhibitors combined with chemotherapy provide superior clinical benefits over chemotherapy alone, albeit with a moderate increase in AEs. However, further verification through multi-center, high-quality RCTs with larger sample sizes is needed to confirm these findings.Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024627485.

Objective To explore the relationship between serum Krüppel-like factor 5(KLF5) and actinin-4 with prognosis of hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization (TACE). Methods From March 2015 to March 2020, 130 HCC patients admitted into the Second Affiliated Hospital were collected as study subjects and divided into HCC group and 86 patients with liver cirrhosis were collected as control group. After 3 years of postoperative follow-up, HCC patients were sub-divided into survival group (n=38) and mortality group (n=92) based on their survival outcomes. ELISA was applied to detect the level of serum KLF5 and actinin-4 in each group and analyzed the correlation between serum KLF5 and actinin-4 levels. Cox regression was applied to analyze the risk factors affecting the prognostic mortality of HCC patients; Receiver operating characteristic curve(ROC) was plotted to evaluate the predictive value of serum KLF5 and actinin-4 levels for the prognostic mortality of HCC patients. Results The serum level of KLF5 and actinin-4 in the mortality group was significantly higher than those in the survival group(P＜0.05); There was a positive correlation between serum level of KLF5 and actinin-4 in HCC patients(P＜0.001); Low differentiation, staging (CNLC) stage IIIa of China liver cancer staging (CNLC), vascular invasion and elevated level of KLF5 and actinin-4 were risk factors for prognostic mortality in HCC patients(P＜0.05); The area under the curve (AUC) of serum KLF5 and actinin-4 alone and in combination for predicting mortality in HCC patients was 0.835, 0.866, and 0.936, respectively, showing a high level of combined predicting function (Zcombination-KLF5=2.792, P=0.005, Zcombination-actinin-4=2.014, P=0.044). Conclusions Serum level of KLF5 and actinin-4 l found in HCC patients has a high predictive value for prognosis.

The reasonable design of hole spacing for buried heat exchangers is the first issue to be solved when developing shallow geothermal energy in the Nanjing erosion and accumulation plain area. In order to obtain the hole spacing for design reference and ensure ground-source heat pump system to operate long and stably, based on the ground-source heat pump test project at No. 102 Shimenkan, Qinhuai District of Nanjing, the hole spacing of ground heat exchanger and time effect of 10-year operation with ground-source heat pump system have been studied with the temperature monitoring system and numerical simulation method, and the hole spacing of ground heat exchanger and the operation mode have been obtained. The results show that : (1) during the complete operation cycle of summer, post summer recovery, winter and post winter recovery working conditions of ground-source heat pump system, formation temperature undergoes periodic change of heating, cooling, slow cooling and basic recovery. (2) The economical and reasonable hole spacing of ground heat exchanger is 4.0 meters suitable for the erosion accumulation plain of Nanjing. (3) In order to eliminate the heat accumulation during the summer working condition and promote the service life of ground-source heat pump system, the operation mode of equal cooling time in the summer and heating time in the winter is suggested, and the post summer recovery working condition is extended as much as possible. This study can provide scientific basis for the design of buried pipes and shallow geothermal energy engineering research in the Nanjing area.

Purpose: To investigate the correlations of spherical equivalent (SE), axial length (AL), and AL to corneal curvature radius ratio (AL/CR) with anterior segment biometrics in candidates for myopic refractive surgery. Methods: Anterior segment biometrics of 2,478 myopic refractive surgery candidates measured by Pentacam were collected retrospectively. The anterior segment biometrics included anterior corneal curvature (ACC), posterior corneal curvature (PCC), white-to-white corneal diameter (WTW), central corneal thickness (CCT), corneal volume at 3 mm (CV), anterior corneal astigmatism (ACA), posterior corneal astigmatism (PCA), anterior corneal eccentricity (ACE), posterior corneal eccentricity (PCE), anterior corneal asphericity (ACAP), posterior corneal asphericity (PCAP), anterior chamber depth (ACD), and anterior chamber volume (ACV). The eyes were divided into four groups according to the AL: group 1, AL≤24 mm; group 2, 24mm

Background: The value of pretreatment baseline 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET)/computed tomography (CT) as a prognostic factor for survival of patients with non-small-cell lung cancer (NSCLC) receiving immunotherapy remained uncertain. Objectives: To investigate the prognostic ability of baseline 18 F-FDG PET/CT in patients with NSCLC receiving immunotherapy. Design: A systematic review and meta-analysis. Data sources and methods: We searched the PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases until May 7, 2024, and extracted data related to patient characteristics, semiquantitative parameters of 18 F-FDG PET/CT, and survival. We pooled hazard ratios (HRs) to evaluate the prognostic value of the maximum standardized uptake value (SUV max ), mean standardized uptake value (SUV mean ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for overall survival (OS) and progression-free survival (PFS). Results: A total of 22 studies (1363 patients, average age range 30–88 years) were included. Baseline 18 F-FDG PET/CT-derived MTV was significantly associated with both OS (HR: 1.124, 95% confidence interval (CI) 1.058–1.195, I 2 = 81.70%) and PFS (HR: 1.069, 95% CI: 1.016–1.124, I 2 = 71.80%). Other baseline 18 F-FDG PET/CT-derived parameters, including SUV max (OS: HR: 0.930, 95% CI: 0.718–1.230; PFS: HR: 0.979, 95% CI: 0.759–1.262), SUV mean (OS: HR: 0.801, 95% CI: 0.549–1.170; PFS: HR: 0.688, 95% CI: 0.464–1.020), and TLG (OS: HR: 0.999, 95% CI: 0.980–1.018; PFS: HR: 0.995, 95% CI: 0.980–1.010), were not associated with survival. Sensitivity analyses by removing one study at a time did not significantly alter the association between MTV and PFS or between MTV and OS. There was no evidence of publication bias. Conclusion: Pretreatment baseline 18 F-FDG PET/CT-derived MTV might be a prognostic biomarker in NSCLC patients receiving immunotherapy. Further studies are needed to support routine use.

Objective: This study aims to assess the risk of neonatal susceptibility to COVID-19 among pregnant women. Methods: We conducted a retrospective cohort study involving 1089 pregnant women ≥28 weeks of gestational age, who were categorized into infected and uninfected groups. Data for all participants were collected through a comprehensive review of electronic medical records and follow-up phone calls. The primary outcome was neonatal infection with SARS-CoV-2, while secondary outcomes included delivery patterns and gestational age at delivery. Results: Maternal vaccination (OR 95%CI:0.63[0.46, 0.85]) and maternal infection with SARS-CoV-2 (OR 95%CI: 0.45[0.34, 0.60]) were found to be associated with a decreased risk of neonatal infection. The infected group exhibited a lower neonatal SARS-CoV-2 infection rate (25.93%) compared to the uninfected group (45.15%). Logistic regression analysis identified several risk factors associated with an increased risk of neonatal infection, including pregnancy BMI (OR 95%CI: 1.04[1.01, 1.08]), age at first pregnancy (OR 95%CI: 1.05[1.01, 1.10]), age at menarche (OR 95%CI: 1.13[1.02, 1.26]), and parturition (Yes vs. No) (OR 95%CI:1.4 [1.04,1.88]). Conclusion: Maternal vaccination and perinatal infection with SARS-CoV-2 play a protective role in preventing neonatal SARS-CoV-2 infection.

Abstract Objective Sodium glucose cotransporter 2 (SGLT2) inhibitors significantly improve cardiovascular outcomes in diabetic patients; however, the mechanism is unclear. We hypothesized that dapagliflozin improves cardiac outcomes via beneficial effects on systemic and cardiac inflammation and cardiac fibrosis. Research and design methods This randomized placebo-controlled clinical trial enrolled 62 adult patients (mean age 62, 17% female) with type 2 diabetes (T2D) without known heart failure. Subjects were randomized to 12 months of daily 10 mg dapagliflozin or placebo. For all patients, blood/plasma samples and cardiac magnetic resonance imaging (CMRI) were obtained at time of randomization and at the end of 12 months. Systemic inflammation was assessed by plasma IL-1B, TNFα, IL-6 and ketone levels and PBMC mitochondrial respiration, an emerging marker of sterile inflammation. Global myocardial strain was assessed by feature tracking; cardiac fibrosis was assessed by T1 mapping to calculate extracellular volume fraction (ECV); and cardiac tissue inflammation was assessed by T2 mapping. Results Between the baseline and 12-month time point, plasma IL-1B was reduced (− 1.8 pg/mL, P = 0.003) while ketones were increased (0.26 mM, P = 0.0001) in patients randomized to dapagliflozin. PBMC maximal oxygen consumption rate (OCR) decreased over the 12-month period in the placebo group but did not change in patients receiving dapagliflozin (− 158.9 pmole/min/106 cells, P = 0.0497 vs. − 5.2 pmole/min/106 cells, P = 0.41), a finding consistent with an anti-inflammatory effect of SGLT2i. Global myocardial strain, ECV and T2 relaxation time did not change in both study groups. Clinical Trial.gov Registration NCT03782259.

Abstract Background Wheat is one of the important grain crops in the world. The formation of lesion spots related to cell death is involved in disease resistance, whereas the regulatory pathway of lesion spot production and resistance mechanism to pathogens in wheat is largely unknown. Results In this study, a pair of NILs (NIL-Lm5 W and NIL-Lm5 M) was constructed from the BC1F4 population by the wheat lesion mimic mutant MC21 and its wild genotype Chuannong 16. The formation of lesion spots in NIL-Lm5 M significantly increased its resistance to stripe rust, and NIL-Lm5 M showed superiour agronomic traits than NIL-Lm5 W under stripe rust infection.Whereafter, the NILs were subjected to transcriptomic (stage N: no spots; stage S, only a few spots; and stage M, numerous spots), metabolomic (stage N and S), and hormone analysis (stage S), with samples taken from normal plants in the field. Transcriptomic analysis showed that the differentially expressed genes were enriched in plant-pathogen interaction, and defense-related genes were significantly upregulated following the formation of lesion spots. Metabolomic analysis showed that the differentially accumulated metabolites were enriched in energy metabolism, including amino acid metabolism, carbohydrate metabolism, and lipid metabolism. Correlation network diagrams of transcriptomic and metabolomic showed that they were both enriched in energy metabolism. Additionally, the contents of gibberellin A7, cis-Zeatin, and abscisic acid were decreased in leaves upon lesion spot formation, whereas the lesion spots in NIL-Lm5 M leaves were restrained by spaying GA and cytokinin (CTK, trans-zeatin) in the field. Conclusion The formation of lesion spots can result in cell death and enhance strip rust resistance by protein degradation pathway and defense-related genes overexpression in wheat. Besides, the formation of lesion spots was significantly affected by GA and CTK. Altogether, these results may contribute to the understanding of lesion spot formation in wheat and laid a foundation for regulating the resistance mechanism to stripe rust.

Phosphoric acid is commonly used to react with carbonates to generate carbon dioxide for determining the carbon and oxygen isotopes of carbonates by using online reaction device, for example, GasBench coupled to an isotope ratio mass spectrometer (IRMS). During the measurement, oxygen isotope fractionation will arise due to various factors, which can result differences between the measured oxygen isotope values and the actual ones. In this study, a series of carbonate standard materials (international standard materials IAEA-603, NBS18, and national standard materials GBW04416 and GBW04405) and modern marine planktonic foraminiferal samples were determined to explore the contribution of acid fractionation on the oxygen isotope values under different conditions. The effects of acid fractionation on the oxygen isotope values for each standard material, and the underlying mechanism were investigated and discussed. The results showed that: 1) The acid fractionation effect is mainly caused by the exchange of oxygen isotopes between the sample CO2 gas and the evaporated gas phase water in the headspace bottle (at high temperatures) or by the liquid water in the acid (at low temperatures); 2) The acid fractionation coefficients of oxygen isotope in carbonate reference materials with different characteristics show significant differences and are related to their oxygen isotope compositions; 3) The degree of deviation of oxygen isotopes is related to the factors such as reaction temperature, sample quantity, water content of phosphoric acid, and the difference between the oxygen isotope composition of liquid and gaseous water in the acid and the oxygen isotope composition of the samples; 4) The acid fractionation effect on oxygen isotopes is significantly correlated with signal intensity. It is recommended to effectively correct the oxygen isotope fractionation of acid by accurately weighing reference materials and samples, following the principle of peak intensity matching and adopting linear correction method for determination of oxygen isotopes in carbonates. Besides, a lower reaction temperature (25 ℃) generates slighter degree of oxygen isotope fractionation. This study provides a useful reference for the accurate determination of carbon and oxygen isotope composition in carbonates, and is of great significance for improving analysis accuracy.

Abstract Background Although papillary thyroid cancer (PTC) patients are known to have an excellent prognosis, up to 30% of patients experience disease recurrence after initial treatment. Accurately predicting disease prognosis remains a challenge given that the predictive value of several predictors remains controversial. Thus, we investigated whether machine learning (ML) approaches based on comprehensive predictors can predict the risk of structural recurrence for PTC patients. Methods A total of 2244 patients treated with thyroid surgery and radioiodine were included. Twenty-nine perioperative variables consisting of four dimensions (demographic characteristics and comorbidities, tumor-related variables, lymph node (LN)-related variables, and metabolic and inflammatory markers) were analyzed. We applied five ML algorithms—logistic regression (LR), support vector machine (SVM), extreme gradient boosting (XGBoost), random forest (RF), and neural network (NN)—to develop the models. The area under the receiver operating characteristic (AUC-ROC) curve, calibration curve, and variable importance were used to evaluate the models’ performance. Results During a median follow-up of 45.5 months, 179 patients (8.0%) experienced structural recurrence. The non-stimulated thyroglobulin, LN dissection, number of LNs dissected, lymph node metastasis ratio, N stage, comorbidity of hypertension, comorbidity of diabetes, body mass index, and low-density lipoprotein were used to develop the models. All models showed a greater AUC (AUC = 0.738 to 0.767) than did the ATA risk stratification (AUC = 0.620, DeLong test: P

Ionospheric plasma density disturbances significantly affect radio wave propagation, impacting communication and planetary exploration. At Earth, sporadic E layers (Es) are commonly observed. They are characterized by thin, high-density plasma structures in the E-region ionosphere, primarily formed by electromagnetic forces induced by horizontal wind shears. Similar sharp vertical electron density changes have also been observed in the topside of the Martian ionosphere by missions like Mars Global Surveyor, Mars Express, and Mars Atmosphere and Volatile EvolutioN. Recent studies suggest that such structures observed on Mars can be attributed to a sporadic E-like mechanism induced by magnetic shear, which can be referred to as Es-like structures. While wind shear theoretically contributes to such events, no observational evidence currently reports wind shear as an explanation for these density gradients on Mars. In this study, we report a novel observation of an Es-like topside layer in the Martian ionosphere, characterized by both density layer and rift (an abrupt depletion in density), where wind and magnetic shear are simultaneously observed. Statistical analysis of 305 orbits with wind speed observations revealed wind shear is observed in nine Es-like events, primarily occurring in strong crustal magnetic field regions. Simulations suggest that the observed rift and layer can be explained either by “wind shear” or by “wind and magnetic shear” under strong crustal magnetic field. This study provides new observations of Es-like events on Mars and serves as a credible candidate for the contribution of wind shear to the formation of an Es-like topside layer.

Objective To explore the prognostic value of serum levels of miR-155 and Smad5 in hemodialysis (HD) patients with acute renal failure (ARF). Methods From August 2018 to July 2019, 120 ARF patients on HD were selected as study group while another 116 healthy subjects as control group; the serum expressions of miR-155 and Smad5 mRNA were detected by quantitative reverse transcriptase-mediated polymerase chain reaction (qRT-PCR). Pearson’s method was utilized for examining the correlation between serum expression levels of miR-155 and Smad5 mRNA and the levels of creatinine and blood urea nitrogen (BUN); Kaplan-Meier method was employed for examining the survival of HD patients with ARF; COX regression for analyzing the prognostic factors; receiver operating characteristic curve (ROC) curve for assessing the predictive value of serum miR-155 and Smad5 mRNA levels. Results The levels of serum miR-155, creatinine and BUN were obviously higher in study group than those in control group (P

Abstract The production of safe and high-quality silage has always been the main concern. This experiment aimed to investigate the impact of waste dried soybean curd residue (SR) and Lactobacillus plantarum CCZZ1 on the fermentation quality and microbial community of total mixed ration (TMR) silage based on Napier grass (Pennisetum purpureum). Napier grass was made into TMR, and SR at 3%, 6% or 9% on dry material basis was included, which replaced the equivalent amount of corn meal, then they were inoculated without or with Lactobacillus plantarum CCZZ1 (105 cfu g−1; LP). The research results showed that incorporating SR even at 3% resulted in significant reduction in ammonia nitrogen content (87.3 g kg−1 total nitrogen vs. 109.7 g kg−1 total nitrogen), increased lactic acid content (34.4 g kg−1 DM vs. 25.5 g kg−1 DM), and higher relative abundance of Lactobacillus (94.5% vs. 32.2%). Additionally, it led to decreased relative abundances of pathogenic microorganisms such as Escherichia coli (

Human immunodeficiency virus-1 (HIV-1) infection can cause chronic activation, exhaustion, and anergy of the immune system. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is an immune checkpoint molecule, which plays an important role in immune homeostasis and disease. CTLA-4 expression is elevated in HIV-1-infected patients and is associated with disease progression. However, the mechanism controlling expression of CTLA-4 in HIV-1 infection is poorly characterized. In this study, we used a SIV-infected Chinese rhesus macaque (ChRM) model to explore CTLA-4 expression in SIV infection. Results showed that SIV infection significantly increased CTLA-4 expression in all T cell subsets, especially central memory T cells. CTLA-4+CD4+ T cell frequency was significantly associated with disease progression markers. Activation of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway regulated CTLA-4 expression in CD4+T cells, as confirmed by stimulation with dibutyryl cyclic adenosine monophosphate, forskolin, and 3-isobutyl-1-methylxanthine, and inhibition with H-89 ex vivo. Simultaneously, cAMP concentration in PBMCs and PKA activity in both PBMCs and CD4+ T cells were increased in acute SIV-infected ChRMs, accompanied by an increase in adenylate cyclase 6 expression and a decrease in cAMP-phosphodiesterase 3A (PDE3A), PDE4B, and PDE5A expression in PBMCs. In addition, selective inhibition of PDE4B and PDE5A activity enhanced CTLA-4 expression in CD4+ T cells. These results suggest that SIV infection alters cAMP metabolism and increases cAMP-PKA signaling pathway activation, which up-regulates the expression of CTLA-4 in acute SIVmac239-infected ChRMs. Thus, regulation of the cAMP-PKA signaling pathway may be a potential strategy for the restoration of T cell function and therapy for AIDS.

Currently, the incidence of prostate cancer is increasing, and it has become a great threat to men’s health. The detection, staging, and follow-up of prostate cancer patients are inseparable from morphology or magnetic resonance imaging (MRI). However, these do not fully meet the needs of diagnosis and patient management. In particular, owing to the late diagnosis, metastatic castration-resistant prostate cancer (mCRPC) patients usually have poor survival and few options for further effective treatment. Prostate-specific membrane antigen (PSMA), because of its overexpression on prostate cancer cells, has gained interest due to its application in the imaging and theranostics field. Several PSMA radioligands have been developed for imaging and treating prostate cancer. Many clinical trials have assessed the efficacy and safety profiles of these radionuclide agents and show promise in patients who have exhausted other standard treatment options. To date, several small compounds for targeting PSMA have been developed, and 68Ga-PSMA-11 and 18F-DCFPyL have been approved by the United States (US) Food and Drug Administration (FDA) for imaging of prostate cancer. 111In- or 99mTc-labeled PSMA-ligand can guide surgeons searching for radioactive metastatic lymph nodes, and 177Lu- or 225Ac-labeled PSMA-ligand can be used for internal radiotherapy. Moreover, some molecules for therapeutic application are undergoing different stages of clinical trials. In this review, we present current perspectives on the use of PSMA-targeted imaging and theranostics in prostate cancer. As PSMA-targeted imaging and therapeutics are becoming the standard of care for prostate cancer patients, we emphasize the importance of integrating nuclear medicine physicians into multidisciplinary oncology teams.

Background: Molecular markers are involved in atopic dermatitis (AD) pathogenesis. The estrogen receptor (ESR)-1 gene, encoding ERα, is reported to express aberrantly in AD patients.Objective: To detect the biological functions of ESR1 in 2,4 dinitrochlorobenzene (DNCB)-treated mice.Methods: The DNCB-treated mice received a topical application of emulsion containing the 1,3-bis(4 hydroxyphenyl)-4-methyl-5-[4-(2-piperidinyl ethoxy) phenol]-1H-pyrazole dihydrochloride (MPP; an ESR1-selective antagonist) to dorsal skins and ears. Then the dermatitis scores, histopathological changes, and cytokine levels were evaluated.Results: MPP specifically downregulated ESR1 expression in DNCB-applied mice. Functionally, application of MPP abolished the DNCB-induced promotion in dermatitis score. Additionally, MPP administration protected against DNCB-induced dermatitis severity, suppressed mast cell infiltration and reduced production of immunoglobulin E (IgE) and thymus and activation-regulated chemokine (TARC). Moreover, MPP treatment inhibited DNCB- induced production of Th2 cytokines and infiltration of CD4+ T cells.Conclusion: ESR1 facilitates Th2-immune response and enhances Th2 cytokines in AD mice.

Abstract Background Filling silos generally takes much time in practice, which may negatively affect silage fermentation and feed intake. To clarify the effects of inoculating time, lactic acid bacteria (LAB) strains and filling time on the silage fermentation and microbes of stylo (Stylosanthes guianensis) and its silage, ensiling was quickly performed (quickly filling, QF) with or without LAB (Lactobacillus plantarum SXC48, Lb. plantarum CCZZ1 and Enterococcus faecalis XC124), and was performed after stylo inoculated with or without LAB was placed for 1 day (delayed filling, DF1) and 2 days (DF2). Results Delayed filling significantly increased pH, buffering capacity, microbial counts and lactic acid, acetic acid and NH3–N contents of stylo prior to ensiling. Inoculating Lb. plantarum SXC48 and CCZZ1 improved the fermentation quality of QF silage, indicated by more lactic acid, as well as lower pH and butyric acid content. Inoculating time significantly affected the pH and lactic acid content of silages. For the DF2 silages, inoculating SXC48 at filling was better than at chopping, while inoculating CCZZ1 had good fermentation quality, regardless of inoculating time. The results of 16S rRNA sequencing indicated that delayed filling enhanced the bacterial diversity of materials and silage, and inoculating significantly changed the composition of silage microbes. Kosakonia, Pseudomonas and Pantoea jointly dominated the fresh material, while Pantoea and Lelliottia jointly dominated the DF2 material. For the QF silages, inoculating SXC48 and CCZZ1 increased the relative abundance of Lactobacillus from 16.4% in the control silage to 76.5% and 82.0%, respectively. Pantoea and Lelliottia jointly dominated the DF silages. Inoculating SXC48 and CCZZ1 also increased the relative abundance of Lactobacillus in the DF stylo silages. Conclusions Under the present research conditions, delayed filling increased the lactic acid content and reduced the acetic acid, propionic acid and NH3–N contents of stylo silage, however, increased the bacterial diversity and relative abundance of undesirable bacteria, such as Pantoea and Lelliottia. The inoculating effectiveness varied with the LAB strains and inoculating time. Inoculating strian SXC48 at filling was better than at chopping, while inoculating strian CCZZ1 at both chopping and filling obtained the similar benefit. Graphical Abstract

We identified a novel circovirus (human-associated circovirus 2 [HuCV2]) from the blood of 2 intravenous drug users in China who were infected with HIV-1, hepatitis C virus, or both. HuCV2 is most closely related to porcine circovirus 3. Our findings underscore the risk for HuCV2 and other emerging viruses among this population.

Abstract Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2. Here we report that nelfinavir, an FDA approved drug for the treatment of HIV infection, is effective against SARS-CoV-2 and COVID-19. Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2 (IC50 = 8.26 μM), while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93 μM (EC50). In comparison with vehicle-treated animals, rhesus macaque prophylactically treated with nelfinavir had significantly lower temperature and significantly reduced virus loads in the nasal and anal swabs of the animals. At necropsy, nelfinavir-treated animals had a significant reduction of the viral replication in the lungs by nearly three orders of magnitude. A prospective clinic study with 37 enrolled treatment-naive patients at Shanghai Public Health Clinical Center, which were randomized (1:1) to nelfinavir and control groups, showed that the nelfinavir treatment could shorten the duration of viral shedding by 5.5 days (9.0 vs. 14.5 days, P = 0.055) and the duration of fever time by 3.8 days (2.8 vs. 6.6 days, P = 0.014) in mild/moderate COVID-19 patients. The antiviral efficiency and clinical benefits in rhesus macaque model and in COVID-19 patients, together with its well-established good safety profile in almost all ages and during pregnancy, indicated that nelfinavir is a highly promising medication with the potential of preventative effect for the treatment of COVID-19.

Abstract In this study, a powerful and rapid aqueous two-phase system (ATPS) method was used to extract polysaccharides from Codonopsis pilosula. The ATPS process was investigated with response surface methodology (RSM). At an ammonium sulfate concentration of 17%, ethanol concentration of 30%, and extraction temperature of 40 °C at pH 6, the total extraction yield of polysaccharides reached (31.57 ± 1.28)%. After separation and purification, a homogenized polysaccharide CPP 2–4 with molecular weight of 3.9 × 104 kDa was obtained from the bottom phase. The physicochemical properties and structural features confirmed that CPP 2–4 was an α-1,6-glucan. Activity studies showed that the IC50 of CPP 2–4 for DPPH radical scavenging was 0.105 mg/mL. The FRAP and ABTS assays showed that CPP 2–4 had strong antioxidant activity in a dose-dependent manner. Furthermore, CPP 2–4 inhibited NO release in RAW264.7 cells induced by lipopolysaccharide, which indicated a certain anti-inflammatory effect. This study improved the extraction rate of polysaccharides from C. pilosula and identified a glucan for the first time, that can contribute to a better understanding of the composition and structure of polysaccharides from C. pilosula and provide data support for the medicine and food homology of C. pilosula.

BackgroundMost instances of small cell carcinoma originate from the lungs, while the gastrointestinal tract serves as a secondary site. Only a minuscule proportion of cases manifest within the urogenital system. Prostate small cell carcinoma (SCCP) represents an exceedingly uncommon pathological subtype within the realm of prostate cancer, displaying significant rarity in clinical settings. This scarcity has resulted in a paucity of adequate foundational and clinical research for SCCP treatment. While investigations have unveiled a certain therapeutic efficacy of radiotherapy and chemotherapy for SCCP, clinical practice has revealed suboptimal treatment outcomes. We hereby present a case report detailing the utilization of 177Lu-DOTA-TATE in the treatment of SCCP, aiming to investigate the therapeutic efficacy of 177Lu-DOTA-TATE for SCCP.Case presentationA male patient in his 80s presented with elevated prostate-specific antigen (PSA) levels and underwent a biopsy that revealed prostate adenocarcinoma. The patient received CAB (bicalutamide + goserelin) therapy. One year later, disease progression was detected, and a second biopsy confirmed the presence of prostate small cell carcinoma. Following the diagnosis of prostate small cell carcinoma, the patient underwent two cycles of 177Lu-DOTA-TATE treatment. Subsequent to the treatment, the original lesions showed shrinkage, metastatic lesions disappeared, and there was significant improvement, approaching complete remission.ConclusionSCCP exhibits a high degree of malignancy and aggressive invasiveness, currently lacking effective therapeutic modalities. The treatment course of this patient serves as compelling evidence for the efficacy of 177Lu-DOTA-TATE in managing SCCP, thereby opening new avenues for future SCCP treatments.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV) and with a high fatality rate. Thrombocytopenia is a major clinical manifestation observed in SFTS patients, but the underlying mechanism remains largely unclear. Here, we explored the effects of SFTSV infection on platelet function in vivo in severely infected SFTSV IFNar−/− mice and on mouse and human platelet function in vitro. Results showed that SFTSV-induced platelet clearance acceleration may be the main reason for thrombocytopenia. SFTSV-potentiated platelet activation and apoptosis were also observed in infected mice. Further investigation showed that SFTSV infection induced platelet reactive oxygen species (ROS) production and mitochondrial dysfunction. In vitro experiments revealed that administration of SFTSV or SFTSV glycoprotein (Gn) increased activation, apoptosis, ROS production, and mitochondrial dysfunction in separated mouse platelets, which could be effectively ameliorated by the application of antioxidants (NAC (N-acetyl-l-cysteine), SKQ1 (10-(6′-plastoquinonyl) decyltriphenylphosphonium) and resveratrol). In vivo experiments showed that the antioxidants partially rescued SFTSV infection-induced thrombocytopenia by improving excessive ROS production and mitochondrial dysfunction and down-regulating platelet apoptosis and activation. Furthermore, while SFTSV and Gn directly potentiated human platelet activation, it was completely abolished by antioxidants. This study revealed that SFTSV and Gn can directly trigger platelet activation and apoptosis in an ROS-MAPK-dependent manner, which may contribute to thrombocytopenia and hemorrhage during infection, but can be abolished by antioxidants.

BackgroundNurses in Ophthalmology Department (OD) had a high risk of infection during the novel coronavirus disease 2019 (COVID-19) pandemic. This study examined the prevalence, correlates, and network structure of depression, and explored its association with quality of life (QOL) in Chinese OD nurses.MethodsBased on a cross-sectional survey, demographic and clinical data were collected. Depression was measured with the 9-item Self-reported Patient Health Questionnaire (PHQ-9), and QOL was measured using the World Health Organization Quality of Life Questionnaire-brief version (WHOQOL-BREF). Univariate analyses, multivariate logistic regression analyses, and network analyses were performed.ResultsAltogether, 2,155 OD nurses were included. The overall prevalence of depression among OD nurses was 32.71% (95%CI: 30.73–34.70%). Multiple logistic regression analysis revealed that having family or friends or colleagues who were infected (OR = 1.760, p = 0.003) was significantly associated with higher risk of depression. After controlling for covariates, nurses with depression reported lower QOL (F(1, 2,155) = 596.784, p

Breast cancer (BC) is a significant cause of cancer-related deaths among women worldwide. Hypoxia, a common feature of solid tumor, is associated with drug resistance and a poor prognosis in BC. In this study, we present a strategy to overcome hypoxia-induced chemotherapy tolerance in BC. Specifically, we synthesized a hollow gold (Au)-platinum (Pt) bimetallic nanoshell for the first time, which acted as a drug delivery system (DDS) for doxorubicin (DOX). The photothermal effect, induced by the surface plasmon resonance (SPR) from the Au-Pt shell under near infrared-II (NIR-II) laser irradiation, not only directly causes tumor cell death through photothermal therapy (PTT), but also significantly enhances the catalase-like activity between Pt nanoparticles and endogenous H2O2. This, subsequently, results in a heightened yield of O2, which further facilitates the release of DOX. This process alleviates tumor hypoxia and down-regulating hypoxia-inducible factor-1α (HIF-1α), multidrug resistance gene 1 (MDR1), and P-glycoprotein (P-gp), which can reverse drug resistance and achieve more effective DOX chemotherapy effects. Significantly, the increased availability of oxygen further re-polarizes immunosuppressive M2 macrophages into antitumor M1 macrophages. This study presents a novel strategy to tackle tumor proliferation and enhance tumor response to chemotherapy, offering hope for reversing in drug resistance in cancerous lesions. [ABSTRACT FROM AUTHOR]

For the demand for long-range and high-resolution target reconstruction of slow-moving small underwater targets, research on single-photon lidar target reconstruction technology is being carried out. This paper reports the sequential multimodal underwater single-photon lidar adaptive target reconstruction algorithm based on spatiotemporal sequence fusion, which has strong information extraction and noise filtering ability and can reconstruct the target depth and reflective intensity information from complex echo photon time counts and spatial pixel relationships. The method consists of three steps: data preprocessing, sequence-optimized extreme value inference filtering, and collaborative variation strategy for image optimization to achieve high-quality target reconstruction in complex underwater environments. Simulation and test results show that the target reconstruction method outperforms the current imaging algorithms, and the built single-photon lidar system achieves underwater lateral and distance resolution of 5 mm and 2.5cm@6AL, respectively. This indicates that the method has a great advantage in sparse photon counting imaging and possesses the capability of underwater target imaging under the background of strong light noise. It also provides a good solution for underwater target imaging of small slow-moving targets with long-distance and high-resolution. [ABSTRACT FROM AUTHOR]

NAD+ boosting via nicotinamide riboside (NR) confers anti-inflammatory effects. However, its underlying mechanisms and therapeutic potential remain incompletely defined. Here, we showed that NR increased the expression of CC-chemokine receptor 7 (CCR7) in human M1 macrophages by flow cytometric analysis of cell surface receptors. Consequently, chemokine ligand 19 (CCL19, ligand for CCR7)-induced macrophage migration was enhanced following NR administration. Metabolomics analysis revealed that prostaglandin E2 (PGE2) was increased by NR in human monocytes and in human serum following in vivo NR supplementation. Furthermore, NR-mediated upregulation of macrophage migration through CCL19/CCR7 was dependent on PGE2 synthesis. We also demonstrated that NR upregulated PGE2 synthesis through SIRT3-dependent post-transcriptional regulation of cyclooxygenase 2 (COX-2). The NR/SIRT3/migration axis was further validated using the scratch-test model where NR and SIRT3 promoted more robust migration across a uniformly disrupted macrophage monolayer. Thus, NR-mediated metabolic regulation of macrophage migration and wound healing may have therapeutic potential for the topical management of chronic wound healing.

Abstract A multifunctional nanoplatform with core–shell structure was constructed in one-pot for the synergistic photothermal, photodynamic, and chemotherapy against breast cancer. In the presence of gambogic acid (GA) as the heat-shock protein 90 (HSP90) inhibitor and the gold nanostars (AuNS) as the photothermal reagent, the assembly of Zr4+ with tetrakis (4-carboxyphenyl) porphyrin (TCPP) gave rise to the nanocomposite AuNS@ZrTCPP-GA (AZG), which in turn, further coated with PEGylated liposome (LP) to enhance the stability and biocompatibility, and consequently the antitumor effect of the particle. Upon cellular uptake, the nanoscale metal − organic framework (NMOF) of ZrTCPP in the resulted AuNS@ZrTCPP-GA@LP (AZGL) could be slowly degraded in the weak acidic tumor microenvironment to release AuNS, Zr4+, TCPP, and GA to exert the synergistic treatment of tumors via the combination of AuNS-mediated mild photothermal therapy (PTT) and TCPP-mediated photodynamic therapy (PDT). The introduction of GA serves to reduce the thermal resistance of the cell to re-sensitize PTT and the constructed nanoplatform demonstrated remarkable anti-tumor activity in vitro and in vivo. Our work highlights a facile strategy to prepare a pH-dissociable nanoplatform for the effective synergistic treatment of breast cancer. Graphical Abstract