Isopsoralen Improves Glucocorticoid-induced Osteoporosis by Regulating Purine Metabolism and Promoting cGMP/PKG Pathway-mediated Osteoblast Differentiation.

BACKGROUND: The effects of Isopsoralen (ISO) in promoting osteoblast differentiation and inhibiting osteoclast formation are well-established, but the mechanism underlying ISO's improvement of Glucocorticoid- Induced Osteoporosis (GIOP) by regulating metabolism remains unclear. METHODS: This study aims to elucidate the mechanism of ISO treatment for GIOP through non-targeted metabolomics based on ISO's efficacy in GIOP. Initially, we established a GIOP female mouse model and assessed ISO's therapeutic effects using micro-CT detection, biomechanical testing, serum calcium (Ca), and phosphorus (P) level detection, along with histological analyses using hematoxylin and eosin (HE), Masson, and tartrate-resistant acidic phosphatase (TRAP) staining. Subsequently, non-targeted metabolomics was employed to investigate ISO's impact on serum metabolites in GIOP mice. RT-qPCR and Western blot analyses were conducted to measure the levels of enzymes associated with these metabolites. Building on the metabolomic results, we explored the effects of ISO on the cyclic Guanosine Monophosphate (cGMP)/Protein Kinase G (PKG) pathway and its role in mediating osteoblast differentiation. RESULTS: Our findings demonstrate that ISO intervention effectively enhances the bone microarchitecture and strength of GIOP mice. It mitigates pathological damage, such as structural damage in bone trabeculae, reduced collagen fibers, and increased osteoclasts, while improving serum Ca and P levels in GIOP mice. Non-- targeted metabolomics revealed purine metabolism as a common pathway between the Control and GIOP groups, as well as between the ISO high-dose (ISOH) group and the GIOP group. ISO intervention upregulated inosine and adenosine levels, downregulated guanosine monophosphate levels, increased Adenosine Deaminase (ADA) expression, and decreased cGMP-specific 3',5'-cyclic phosphodiesterase (PDE5) expression. Additionally, ISO intervention elevated serum cGMP levels, upregulated PKGI and PKGII expression in bone tissues, as well as the expression of Runt-related transcription factor 2 (Runx2) and Osterix, and increased serum Alkaline Phosphatase (ALP) activity. CONCLUSION: In summary, ISO was able to enhance the bone microstructure and bone strength of GIOP mice and improve their Ca, P, and ALP levels, which may be related to ISO's regulation of purine metabolism and promotion of osteoblast differentiation mediated by the cGMP/PKG pathway. This suggests that ISO is a potential drug for treating GIOP. However, further research is still needed to explore the specific targets and clinical applications of ISO.

Solid-State Synthesis of Na4Fe3(PO4)2P2O7/C by Ti-Doping with Promoted Structural Reversibility for Long-Cycling Sodium-Ion Batteries.

The cathode material Na4Fe3(PO4)2P2O7 (NFPP) has shown great potential for sodium-ion batteries (SIBs) due to its cost-effectiveness, prolonged cycle life, and high theoretical capacity. However, the practical large-scale production of NFPP is hindered by its poor intrinsic electron conductivity and the presence of a NaFePO4 impurity. In this study, we propose a mutually reinforcing approach involving Ti doping, mechanical nano treatment, and in situ carbon coating to produce Ti-NFPP via the solid-state methods of synthesis. Ti doping strengthens the covalent Fe-O interaction, hence accelerating the electron transfer and the redox reactions Fe2+/Fe3+. In situ carbon coating improves electrical conductivity and allows for accommodating the volumetric variation. Nanosized treatment promotes the uniform progression of solid-state reactions. The synthesized Na4Fe2.98Ti0.01(PO4)2P2O7 material (Ti-NFPP) exhibits promising electrochemical properties with an initial discharge specific capacity of 112.5 mA h g-1 at 0.1 C. A volumetric change of only 2.98% was observed during the de/sodiation process, indicating an enhanced reversibility of the crystal lattice. Moreover, it demonstrates exceptional cycling stability with a capacity retention rate of 97.2 mA h g-1 at 10 C over 5000 cycles. These findings offer a promising pathway for the large-scale production of Ti-NFPP in SIBs.

Secular trends of dental caries and association with nutritional status: a retrospective analysis of 16,199 Chinese students from three successive national surveys from 2010 to 2019.

Introduction: The prevalence of dental caries (DC) among students in developing countries has increased at an alarming rate, and nutritional status has been shown to be associated with DC in children and adolescents with inconsistent conclusions. We aimed to understand the trends of DC prevalence in students aged 7, 9, 12, and 14 years and to explore the relationship between DC prevalence and nutritional status. Methods: We recruited 16,199 students aged 7, 9, 12, and 14 years in China by multi-stage, stratified, random sampling methods from 2010 to 2019. Permanent caries were measured using the Decay, Loss, and Filling (DMF) index and prevalence rate. Deciduous caries were measured using the decay, loss, and filling (dmf) index and prevalence rate. Nutritional status was assessed using body mass index (BMI) and hemoglobin levels. Logistic regression analysis was used to assess the association between nutritional status and the DC prevalence in children and adolescents, incorporating information concerning family-related factors. Results: The results indicated that DC prevalence increased from 39.75% in 2010 to 53.21% in 2019 in Henan province, with deciduous teeth and permanent teeth being 45.96 and 27.18%, respectively, in 2019. The total caries rate decreased with age (p < 0.05), and the caries rate of girls was higher than that of boys in 2019 (55.75% vs. 50.67%) (p < 0.001). The prevalence of dental caries among primary and secondary school students in areas with medium economic aggregate was the highest, followed by cities with the best economic development level, and cities with low economic levels have a lower prevalence of dental caries. The dental caries prevalence was negatively correlated with body mass index. In the fully adjusted model, underweight children had a higher caries prevalence (OR = 1.10, 95%CI: 0.86-1.41). Children with anemia had a higher prevalence of dental caries (OR = 1.18, 95%CI: 0.98-1.42). Conclusion: The DC prevalence of students in Henan Province was high, with a tendency to increase. Females, young individuals, and those with a higher economic level showed a positive correlation with the prevalence of caries. In the process of economic development, particular attention should be paid to early childhood caries prevention. Nutritional status should be taken seriously among children and adolescents, and the oral health system should be improved to keep pace with economic development.

Heterostructured MnSe/FeSe nanorods encapsulated by carbon with enhanced Na+ diffusion as anode materials for sodium-ion batteries.

The natural abundance of sodium has fostered the development of sodium-ion batteries for large-scale energy storage. However, the low capacity of the anodes hinders their future application. Herein, carbon-encapsulated MnSe-FeSe nanorods (MnSe-FeSe@C) have been fabricated by the in-situ transformation from polydopamine-coated MnO(OH)-Fe2O3. The heterostructure constructed by MnSe and FeSe nanocrystals induces the formation of built-in electric fields, accelerating electron transfer and ion diffusion, thereby improving reaction kinetics. In addition, carbon enclosure can buffer the volumetric stress and enhance the electrical conductivity. These aspects cooperatively endow the anode with superior cycling stability and distinguished rate performance. Specifically, the discharge capacity of MnSe-FeSe@C reaches 414.3 mA h g-1 at 0.1 A g-1 and 388.8 mA h g-1 even at a high current density of 5.0 A g-1. In addition, it still retains a high reversible capacity of 449.2 mA h g-1 after 700 long cycles at 1.0 A g-1. Further, the ab initio calculation has been employed to authenticate the existence of the built-in electric field by Bader charge, indicating that 0.24 electrons in MnSe were transferred to FeSe. The in-situ XRD has been used to evaluate the phase transition during the charging/discharging process, revealing the sodium ion storage mechanism. The construction of heterostructure material paves a new way to design performance-enhanced anode materials for sodium-ion batteries.

Toxic effects and mechanisms of chronic cadmium exposure on Litopenaeus vannamei growth performance based on combined microbiome and metabolome analysis.

Cadmium (Cd) pollution seriously affects marine organisms' health and poses a threat to food safety. Although Cd pollution has attracted widespread attention in aquaculture, little is known about the toxic mechanisms of chronic Cd exposure on shrimp growth performance. The study investigated the combined effects of chronic exposure to Cd of different concentrations including 0, 75, 150, and 300 µg/L for 30 days on the growth performance, tissue bioaccumulation, intestinal microbiology, and metabolic responses of Litopenaeus vannamei. The results revealed that the growth was significantly inhibited under exposure to 150 and 300 µg/L Cd2+. The bioaccumulation in gills and intestines respectively showed an increasing and inverted "U" shaped trend with increasing Cd2+ concentration. Chronic Cd altered the intestinal microflora with a significant decrease in microbial richness and increasing trends in the abundances of the potentially pathogenic bacteria Vibrio and Maribacter at exposure to 75 and 150 µg/L Cd2+, and Maribacter at 300 µg/L. In addition, chronic Cd interfered with intestinal metabolic processes. The expressions of certain metabolites associated with growth promotion and enhanced antioxidant power, including N-methyl-D-aspartic acid, L-malic acid, guanidoacetic acid, betaine, and gluconic acid were significantly down-regulated, especially at exposure to 150 and 300 µg/L Cd2+, and were negatively correlated with Vibrio and Maribacter abundance levels. In summary, chronic Cd exposure resulted in severe growth inhibition and increased Cd accumulation in shrimp tissues. Increased levels of intestinal pathogenic bacteria and decreased levels of growth-promoting metabolites may be the key causes of growth inhibition. Harmful bacteria Vibrio and Maribacter may be associated with the inhibition of growth-promoting metabolite expression and may be involved in disrupting intestinal metabolic functions, ultimately impairing shrimp growth potential. This study sheds light on the potential toxicological mechanisms of chronic Cd inhibition on shrimp growth performance, offering new insights into Cd toxicity studies in aquaculture.

Pd/NHC catalyzed reduction and coupling of nitroaromatics for the synthesis of diarylamines.

Herein, we report a one-pot approach to diarylamines through the reductive homocoupling of nitroaromatics, employing triethylsilane as the reducing agent and Pd/NHC as the catalyst. This method enables nitroaromatics to serve both as electrophilic reagents and as precursors of nucleophilic reagents, allowing for the direct preparation of diarylamines without the need to isolate aromatic primary amines.

Physical frailty, genetic predisposition, and incident dementia: a large prospective cohort study.

Physical frailty and genetic factors are both risk factors for increased dementia; nevertheless, the joint effect remains unclear. This study aimed to investigated the long-term relationship between physical frailty, genetic risk, and dementia incidence. A total of 274,194 participants from the UK Biobank were included. We applied Cox proportional hazards regression models to estimate the association between physical frailty and genetic and dementia risks. Among the participants (146,574 females [53.45%]; mean age, 57.24 years), 3,353 (1.22%) new-onset dementia events were recorded. Compared to non-frailty, the hazard ratio (HR) for dementia incidence in prefrailty and frailty was 1.396 (95% confidence interval [CI], 1.294-1.506, P < 0.001) and 2.304 (95% CI, 2.030-2.616, P < 0.001), respectively. Compared to non-frailty and low polygenic risk score (PRS), the HR for dementia risk was 3.908 (95% CI, 3.051-5.006, P < 0.001) for frailty and high PRS. Furthermore, among the participants, slow walking speed (HR, 1.817; 95% CI, 1.640-2.014, P < 0.001), low physical activity (HR, 1.719; 95% CI, 1.545-1.912, P < 0.001), exhaustion (HR, 1.670; 95% CI, 1.502-1.856, P < 0.001), low grip strength (HR, 1.606; 95% CI, 1.479-1.744, P < 0.001), and weight loss (HR, 1.464; 95% CI, 1.328-1.615, P < 0.001) were independently associated with dementia risk compared to non-frailty. Particularly, precise modulation for different dementia genetic risk populations can also be identified due to differences in dementia risk resulting from the constitutive pattern of frailty in different genetic risk populations. In conclusion, both physical frailty and high genetic risk are significantly associated with higher dementia risk. Early intervention to modify frailty is beneficial for achieving primary and precise prevention of dementia, especially in those at high genetic risk.

Using an ER-specific optogenetic mechanostimulator to understand the mechanosensitivity of the endoplasmic reticulum.

The ability of cells to perceive and respond to mechanical cues is essential for numerous biological activities. Emerging evidence indicates important contributions of organelles to cellular mechanosensitivity and mechanotransduction. However, whether and how the endoplasmic reticulum (ER) senses and reacts to mechanical forces remains elusive. To fill the knowledge gap, after developing a light-inducible ER-specific mechanostimulator (LIMER), we identify that mechanostimulation of ER elicits a transient, rapid efflux of Ca2+ from ER in monkey kidney COS-7 cells, which is dependent on the cation channels transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and polycystin-2 (PKD2) in an additive manner. This ER Ca2+ release can be repeatedly stimulated and tuned by varying the intensity and duration of force application. Moreover, ER-specific mechanostimulation inhibits ER-to-Golgi trafficking. Sustained mechanostimuli increase the levels of binding-immunoglobulin protein (BiP) expression and phosphorylated eIF2α, two markers for ER stress. Our results provide direct evidence for ER mechanosensitivity and tight mechanoregulation of ER functions, placing ER as an important player on the intricate map of cellular mechanotransduction.

Exosomal miRNA-92a derived from cancer-associated fibroblasts promote invasion and metastasis in breast cancer by regulating G3BP2.

Cancer-associated Fibroblasts (CAFs) exert a tumor-promoting effect in various cancers, including breast cancer. CAFs secrete exosomes containing miRNA and proteins, influencing the tumor microenvironment. In this study, we identified CAF-derived exosomes that transport functional miR-92a from CAFs to tumor cells, thereby intensifying the aggressiveness of breast cancer. CAFs downregulate the expression of G3BP2 in breast cancer cells, and a significant elevation in miR-92a levels in CAF-derived exosomes was observed. Both in vitro and in vivo experiments demonstrate that miR-92a enhances breast cancer cell migration and invasion by directly targeting G3BP2, functioning as a tumor-promoting miRNA. We validated that the RNA-binding proteins SNRPA facilitate the transfer of CAF-derived exosomal miR-92a to breast cancer cells. The reduction of G3BP2 protein by CAF-derived exosomes releases TWIST1 into the nucleus, promoting epithelial-mesenchymal transition (EMT) and further exacerbating breast cancer progression. Moreover, CAF-derived exosomal miR-92a induces tumor invasion and metastasis in mice. Overall, our study reveals that CAF-derived exosomal miR-92a serves as a promoter in the migration and invasion of breast cancer cells by reducing G3BP2 and may represent a potential novel tumor marker for breast cancer.

GATA3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in breast cancer.

BACKGROUND: Inadequate DNA damage repair promotes aberrant differentiation of mammary epithelial cells. Mammary luminal cell fate is mainly determined by a few transcription factors including GATA3. We previously reported that GATA3 functions downstream of BRCA1 to suppress aberrant differentiation in breast cancer. How GATA3 impacts DNA damage repair preventing aberrant cell differentiation in breast cancer remains elusive. We previously demonstrated that loss of p18, a cell cycle inhibitor, in mice induces luminal-type mammary tumors, whereas depletion of either Brca1 or Gata3 in p18 null mice leads to basal-like breast cancers (BLBCs) with activation of epithelial-mesenchymal transition (EMT). We took advantage of these mutant mice to examine the role of Gata3 as well as the interaction of Gata3 and Brca1 in DNA damage repair in mammary tumorigenesis. RESULTS: Depletion of Gata3, like that of Brca1, promoted DNA damage accumulation in breast cancer cells in vitro and in basal-like breast cancers in vivo. Reconstitution of Gata3 improved DNA damage repair in Brca1-deficient mammary tumorigenesis. Overexpression of GATA3 promoted homologous recombination (HR)-mediated DNA damage repair and restored HR efficiency of BRCA1-deficient cells. Depletion of Gata3 sensitized tumor cells to PARP inhibitor (PARPi), and reconstitution of Gata3 enhanced resistance of Brca1-deficient tumor cells to PARP inhibitor. CONCLUSIONS: These results demonstrate that Gata3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in mammary tumorigenesis and progression. Our findings suggest that PARP inhibitors are effective for the treatment of GATA3-deficient BLBCs.

N6022 attenuates cerebral ischemia/reperfusion injury-induced microglia ferroptosis by promoting Nrf2 nuclear translocation and inhibiting the GSNOR/GSTP1 axis.

Stroke poses a significant risk of mortality, particularly among the elderly population. The pathophysiological process of ischemic stroke is complex, and it is crucial to elucidate its molecular mechanisms and explore potential protective drugs. Ferroptosis, a newly recognized form of programmed cell death distinct from necrosis, apoptosis, and autophagy, is closely associated with the pathophysiology of ischemic stroke. N6022, a selective inhibitor of S-nitrosoglutathione reductase (GSNOR), is a "first-in-class" drug for asthma with potential therapeutic applications. However, it remains unclear whether N6022 exerts protective effects in ischemic stroke, and the precise mechanisms of its action are unknown. This study aimed to investigate whether N6022 mitigates cerebral ischemia/reperfusion (I/R) injury by reducing ferroptosis and to elucidate the underlying mechanisms. Accordingly, we established an oxygen-glucose deprivation/reperfusion (OGD/R) cell model and a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to mimic cerebral I/R injury. Our data, both in vitro and in vivo, demonstrated that N6022 effectively protected against I/R-induced brain damage and neurological deficits in mice, as well as OGD/R-induced BV2 cell damage. Mechanistically, N6022 promoted Nrf2 nuclear translocation, enhancing intracellular antioxidant capacity of SLC7A11-GPX4 system. Furthermore, N6022 interfered with the interaction of GSNOR with GSTP1, thereby boosting the antioxidant capacity of GSTP1 and attenuating ferroptosis. These findings provide novel insights, showing that N6022 attenuates microglial ferroptosis induced by cerebral I/R injury through the promotion of Nrf2 nuclear translocation and inhibition of the GSNOR/GSTP1 axis.

Electrical feedback system for enhancing the RF power of photodetector.

In this paper, we propose a system for enhancing the RF output power of the photodetector, especially the power of fundamental tune and second-order harmonic, by feeding back part of the RF signal through an electrical feedback circuit. As a result of bias modulation and opto-electric mixing, the RF output power can be effectively enhanced. The structure of uni-traveling carrier photodetector (UTC-PD) is employed in this work. With the RF enhancement system, the power of fundamental tune and second-order harmonic improve by 6.4 dB and 9.9 dB respectively, under the condition of 26 dBm input optical power, 3 V bias voltage, and 14 GHz input optical signal. Further, it was observed that third-order harmonic appeared under the influence of this system.

Cerebral Palsy Heterogeneity: Clinical Characteristics and Diagnostic Significance from a Large-Sample Analysis.

INTRODUCTION: Cerebral palsy (CP) is a nonprogressive movement disorder resulting from a prenatal or perinatal brain injury that benefits from early diagnosis and intervention. The timing of early CP diagnosis remains controversial, necessitating analysis of clinical features in a substantial cohort. METHODS: We retrospectively reviewed medical records from a university hospital, focusing on children aged ≥24 months or followed up for ≥24 months and adhering to the International Classification of Diseases-10 for diagnosis and subtyping. RESULTS: Among the 2012 confirmed CP cases, 68.84% were male and 51.44% had spastic diplegia. Based on the Gross Motor Function Classification System (GMFCS), 62.38% were in levels I and II and 19.88% were in levels IV and V. Hemiplegic and diplegic subtypes predominantly fell into levels I and II, while quadriplegic and mixed types were mainly levels IV and V. White matter injuries appeared in 46.58% of cranial MRI findings, while maldevelopment was rare (7.05%). Intellectual disability co-occurred in 43.44% of the CP cases, with hemiplegia having the lowest co-occurrence (20.28%, 58/286) and mixed types having the highest co-occurrence (73.85%, 48/65). Additionally, 51.67% (697/1,349) of the children with CP aged ≥48 months had comorbidities. CONCLUSIONS: This study underscores white matter injury as the primary CP pathology and identifies intellectual disability as a common comorbidity. Although CP can be identified in infants under 1 year old, precision in diagnosis improves with development. These insights inform early detection and tailored interventions, emphasizing their crucial role in CP management.

CNPY2 governs PDGF­BB­treated vascular smooth muscle cell proliferation, migration and phenotypic transformation via the Akt/mTOR/GSK­3ß signaling pathway.

Phenotype switching of vascular smooth muscle cells (VSMCs) is a pathological process in various vascular diseases. Canopy FGF signaling regulator 2 (CNPY2) has previously been found to be abnormally expressed in ApoE-/- mice and aortic endothelial cells, indicating it may have an important role in vascular diseases. The present study aimed to determine the role and mechanism of CNPY2 in VSMC phenotype switching. Following stimulation with platelet-derived growth factor type BB (PDGF-BB), the expression of CNPY2 in VSMCs was detected using reverse transcription-quantitative PCR and western blot analysis. Subsequently, to explore the regulatory effects of CNPY2 on VSMCs, CNPY2 expression was knocked down by transfection with short hairpin RNA and cell viability, proliferation, migration and phenotypic transformation indicators were detected. Western blot analysis was also used to detect the phosphorylation of Akt/mTOR/GSK-3ß pathway-associated proteins downstream of CNPY2. In addition, pretreatment with the Akt pathway activator SC79 was performed to further explore the regulatory mechanisms of CNPY2. The results revealed that CNPY2 expression was upregulated in PDGF-BB-stimulated VSMCs. In addition, the knockdown of CNPY2 inhibited PDGF-BB-induced VSMC hyperproliferation, cell cycle arrest, migration and phenotypic transformation, as well the activation of Akt/mTOR/GSK-3ß pathway-associated proteins. Pretreatment with SC79 significantly reversed the inhibitory effects of CNPY2 knockdown on the proliferation, cell cycle arrest, migration and phenotypic transformation of the model cells. In summary, the present study indicates that CNPY2 regulates the abnormal proliferation, migration and phenotypic transformation of PDGF-BB-stimulated VSMCs via activation of the Akt/mTOR/GSK-3ß signaling pathway.

Correlation between lesion location and dysphagia characteristics in post-stroke patients.

OBJECTIVE: To assess the correlation between lesion location and swallowing function characteristics in post-stroke dysphagia (PSD) patients. MATERIALS AND METHODS: We enrolled 133 PSD. The patients were divided into supratentorial and infratentorial stroke groups. We compared the measurements in the videofluoroscopic swallowing study (VFSS) with 3ml and 5 ml of diluted and thickened barium liquid data between supratentorial and brainstem stroke groups. We further compared the difference of VFSS measurements between patients with left hemispheric or right hemispheric lesions (further divided into unilateral hemispheric cortical and subcortical subgroups) and brianstem leison stroke group.To explore the lesion location's effect on different bolus volume, the VFSS measurements of 3ml and 5ml in each subgroups were compared respectively. The measurements of VFSS included the oral transit time, soft palate elevation duration, hyoid bone movement duration (HMD), UES opening duration, pharyngeal transit duration (PTD), stage of ansition duration, and laryngeal closure duration (LCD), the upper esophageal sphincter opening (UESO), hyoid bone superior horizontal displacement, and hyoid bone anterior horizontal displacement. General swallowing function was assessed using the Penetration Aspiration Scale (PAS) and Functional Oral Intake Scale (FOIS). We performed the paired t-test, Spearman's correlation, and Kruskal-Wallis test analysis to characterize the parameters among the groups. RESULTS: Fifty-eight patients were assessed in the final analysis. The HMD (p = 0.019), PTD (p = 0.048) and LCD (p = 0.013) were significantly different between the supratentorial and brainstem lesion groups in 5ml volume. The HMD was significantly different (p = 0.045) between the left cortical and brainstem lesion groups. Significant differences in the HMD (p = 0.037) and LCD (p = 0.032) between the left subcortical and brainstem lesion groups were found in 5ml volume bolus. There was no group different when taking the 3ml volume bolus. Regarding the relationship between food bolus volume and swallowing functions, only the UESO demonstrated a significant difference in the subcortical lesion of the right hemisphere (p = 0.0032) compared the 3 ml and 5 ml volume bolus. The PTD demonstrated a moderate correlation with the PAS scores (r = 0.38, p = 0.0044). The HMD (r = 0.32, p = 0.018) and LCD (r = 0.29, p = 0.039) demonstrated weak correlations with the PAS scores. We did not identify any correlation between the VFSS parameters and FOIS scores in each subgroup level. CONCLUSION: The PSD with brainstem lesion shows more sever dysfunction in the pharyngeal phases. The left hemisphere was engaged in both the oral and pharyngeal phases. Lesions in the bilateral cortical, subcortical, and brainstem regions may impair sensory input.

Dynamic monitoring of neutrophil/lymphocyte ratio, APACHE II score, and SOFA score predict prognosis and drug resistance in patients with Acinetobacter baumannii-calcoaceticus complex bloodstream infection: a single-center retrospective study.

Objective: This study aimed to evaluate the clinical value of dynamic monitoring of neutrophil/lymphocyte ratio (NLR), APACHE II (Acute Physiology and Chronic Health Evaluation II) score, and Sequential Organ Failure Assessment (SOFA) score in predicting 28-day prognosis and drug resistance in patients with bloodstream infection with Acinetobacter baumannii-calcoaceticus complex (Abc complex). Patients and methods: In this research, individuals admitted to Tianjin Medical University General Hospital from January 2017 to March 2023 with bloodstream infections and a minimum of one Abc complex positive blood culture were chosen. The risk factors for the 28-day prognosis and drug resistance were analyzed using logistic regression. The NLR, APACHE II score, and SOFA score were evaluated for predicting 28-day prognosis and drug resistance using an ROC curve analysis. The data were analyzed using R Studio to find correlations and conduct survival analysis with the Kaplan-Meier method. Results: The final statistical analysis included a total of 129 patients with bloodstream infections caused by Abc complex. Independent risk factors predicting mortality within 28 days were identified as follows: the SOFA score and APACHE II scores at 24 h, and APACHE II scores at 72 h after the onset of blood infection (p < 0.05). NLR, SOFA score, and APACHE II score did not predict drug resistance. Patients with Carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (CRAB) had shorter survival times than those with carbapenem-sensitive strains (40.77 days vs. 47.65 days, respectively, p = 0.0032). Conclusion: The prognosis of Abc complex bloodstream infection is affected by both SOFA and APACHE II scores. Both scoring systems have similar prognostic values at different time points after infection, but for computational convenience, it is recommended to use the SOFA score. NLR exhibits limited effectiveness in predicting mortality within 28 days. Carbapenem-resistant individuals with Abc complex experience significantly reduced survival time. None of the three factors-SOFA score, APACHE II score, and NLR-can early predict the occurrence of CRAB infections effectively.

The relationship between cancer associated fibroblasts biomarkers and prognosis of breast cancer: a systematic review and meta-analysis.

Background: To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting treatment. Methodology: PubMed, Web of Science, Cochrane, and Embase databases were searched for CAFs-related studies of breast cancer patients from their inception to September, 2023. Meta-analysis was performed using R 4.2.2 software. Sensitivity analyses were performed to explore the sources of heterogeneity. Funnel plot and Egger's test were used to assess the publication bias. Results: Twenty-seven studies including 6,830 patients were selected. Univariate analysis showed that high expression of platelet-derived growth factor receptor-ß (PDGFR-ß) (P = 0.0055), tissue inhibitor of metalloproteinase-2 (TIMP-2) (P < 0.0001), matrix metalloproteinase (MMP) 9 (P < 0.0001), MMP 11 (P < 0.0001) and MMP 13 (P = 0.0009) in CAFs were correlated with reduced recurrence-free survival (RFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/event-free survival (EFS) respectively. Multivariate analysis showed that high expression of α-smooth muscle actin (α-SMA) (P = 0.0002), podoplanin (PDPN) (P = 0.0008), and PDGFR-ß (P = 0.0470) in CAFs was associated with reduced RFS/DFS/MFS/EFS respectively. Furthermore, PDPN and PDGFR-ß expression in CAFs of poorly differentiated breast cancer patients were higher than that of patients with relatively better differentiated breast cancer. In addition, there is a positive correlation between the expression of PDPN and human epidermal growth factor receptor-2 (HER-2). Conclusions: The high expression of α-SMA, PDPN, PDGFR-ß in CAFs leads to worse clinical outcomes in breast cancer, indicating their roles as prognostic biomarkers and potential therapeutic targets.

Global research trends in tongue cancer from 2000 to 2022: bibliometric and visualized analysis.

OBJECTIVES: This study conducts a systematic bibliometric analysis of tongue cancer publications to identify key topics, hotspots, and research distribution. METHODS: We analyzed tongue cancer publications in the Web of Science core collection database, assessing their quantity and quality. We investigated contributors, including countries, affiliations, journals, authors, and categories, within collaborative networks. Additionally, we synthesized key research findings using various analytical techniques, such as alluvial flow, burstness analysis, cluster analysis, co-occurrence network of associations, and network layer overlay. RESULTS: From 2000 to 2022, this bibliometric study covers 2205 articles and reviews across 617 journals, involving 72 countries, 2233 institutions, and 11,266 authors. It shows consistent growth, particularly in 2016. Key contributors include China (499 publications), Karolinska Institute (84 publications), Oral Oncology (144 publications), and Tuula Salo (47 publications). Other notable contributors are the USA (16,747 citations), the National Cancer Institute (NCI) (2597 citations), and the Memorial Sloan-Kettering Cancer Center (MSK) (2231 citations). Additionally, there are significant teams led by Tuula Salo and Dalianis. We have identified six primary clusters: #0 apoptosis, #1 depth of invasion, #2 radiotherapy, #3 hpv, #4 tongue cancer, #5 oral cancer. The top ten highly cited documents primarily pertain to epidemiology, prognostic indicators in early-stage oral tongue cancer, and HPV. Additionally, we observed 16 reference clusters, with depth of invasion (#3), young patients (#4), and tumor budding (#6) gaining prominence since 2012, indicating sustained research interests. CONCLUSIONS: This analysis emphasizes the increasing scholarly interest in tongue cancer research. The bibliometric evaluation highlights pivotal recent research themes such as HPV, depth of invasion, tumor budding, and surgical margins. CLINICAL RELEVANCE: The bibliometric analysis highlights the key topics and studies which have shaped the understanding and management of tongue cancer.

Global freshwater fish invasion linked to the presence of closely related species.

In the Anthropocene, non-native freshwater fish introductions and translocations have occurred extensively worldwide. However, their global distribution patterns and the factors influencing their establishment remain poorly understood. We analyze a comprehensive database of 14953 freshwater fish species across 3119 river basins and identify global hotspots for exotic and translocated non-native fishes. We show that both types of non-native fishes are more likely to occur when closely related to native fishes. This finding is consistent across measures of phylogenetic relatedness, biogeographical realms, and highly invaded countries, even after accounting for the influence of native diversity. This contradicts Darwin's naturalization hypothesis, suggesting that the presence of close relatives more often signifies suitable habitats than intensified competition, predicting the establishment of non-native fish species. Our study provides a comprehensive assessment of global non-native freshwater fish patterns and their phylogenetic correlates, laying the groundwork for understanding and predicting future fish invasions in freshwater ecosystems.

Therapeutic strategies targeting the NLRP3­mediated inflammatory response and pyroptosis in cerebral ischemia/reperfusion injury (Review).

Ischemic stroke poses a major threat to human health. Therefore, the molecular mechanisms of cerebral ischemia/reperfusion injury (CIRI) need to be further clarified, and the associated treatment approaches require exploration. The NOD­like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome serves an important role in causing CIRI, and its activation exacerbates the underlying injury. Activation of the NLRP3 inflammasome triggers the maturation and production of the inflammatory molecules IL­1ß and IL­18, as well as gasdermin­D­mediated pyroptosis and CIRI damage. Thus, the NLRP3 inflammasome may be a viable target for the treatment of CIRI. In the present review, the mechanisms of the NLRP3 inflammasome in the intense inflammatory response and pyroptosis induced by CIRI are discussed, and the therapeutic strategies that target the NLRP3­mediated inflammatory response and pyroptosis in CIRI are summarized. At present, certain drugs have already been studied, highlighting future therapeutic perspectives.