Paris saponin VII reverses resistance to PARP inhibitors by regulating ovarian cancer tumor angiogenesis and glycolysis through the RORα/ECM1/VEGFR2 signaling axis.

The emergence of Poly (ADP-ribose) polymerase inhibitors (PARPi) has marked the beginning of a precise targeted therapy era for ovarian cancer. However, an increasing number of patients are experiencing primary or acquired resistance to PARPi, severely limiting its clinical application. Deciphering the underlying mechanisms of PARPi resistance and discovering new therapeutic targets is an urgent and critical issue to address. In this study, we observed a close correlation between glycolysis, tumor angiogenesis, and PARPi resistance in ovarian cancer. Furthermore, we discovered that the natural compound Paris saponin VII (PS VII) partially reversed PARPi resistance in ovarian cancer and demonstrated synergistic therapeutic effects when combined with PARPi. Additionally, we found that PS VII potentially hindered glycolysis and angiogenesis in PARPi-resistant ovarian cancer cells by binding and stabilizing the expression of RORα, thus further inhibiting ECM1 and interfering with the VEGFR2/FAK/AKT/GSK3ß signaling pathway. Our research provides new targeted treatment for clinical ovarian cancer therapy and brings new hope to patients with PARPi-resistant ovarian cancer, effectively expanding the application of PARPi in clinical treatment.

Recent progress in multifunctional, reconfigurable, integrated liquid metal-based stretchable sensors and standalone systems.

Possessing a unique combination of properties that are traditionally contradictory in other natural or synthetical materials, Ga-based liquid metals (LMs) exhibit low mechanical stiffness and flowability like a liquid, with good electrical and thermal conductivity like metal, as well as good biocompatibility and room-temperature phase transformation. These remarkable properties have paved the way for the development of novel reconfigurable or stretchable electronics and devices. Despite these outstanding properties, the easy oxidation, high surface tension, and low rheological viscosity of LMs have presented formidable challenges in high-resolution patterning. To address this challenge, various surface modifications or additives have been employed to tailor the oxidation state, viscosity, and patterning capability of LMs. One effective approach for LM patterning is breaking down LMs into microparticles known as liquid metal particles (LMPs). This facilitates LM patterning using conventional techniques such as stencil, screening, or inkjet printing. Judiciously formulated photo-curable LMP inks or the introduction of an adhesive seed layer combined with a modified lift-off process further provide the micrometer-level LM patterns. Incorporating porous and adhesive substrates in LM-based electronics allows direct interfacing with the skin for robust and long-term monitoring of physiological signals. Combined with self-healing polymers in the form of substrates or composites, LM-based electronics can provide mechanical-robust devices to heal after damage for working in harsh environments. This review provides the latest advances in LM-based composites, fabrication methods, and their novel and unique applications in stretchable or reconfigurable sensors and resulting integrated systems. It is believed that the advancements in LM-based material preparation and high-resolution techniques have opened up opportunities for customized designs of LM-based stretchable sensors, as well as multifunctional, reconfigurable, highly integrated, and even standalone systems.

LADRC-based grid-connected control strategy for single-phase LCL-type inverters.

To ensure that grid-connected currents are of high quality, it is crucial to optimize the dynamic performance of grid-connected inverters and their control. This study suggests using a combination of reduced-order linear active disturbance rejection control (LADRC) and a Proportional-Integral (PI) controller. By applying this control strategy to a single-phase photovoltaic grid-connected system, the system's ability to suppress grid harmonics is significantly improved. The validity and effectiveness of this control approach have been confirmed through simulations and experiments. The results show that the LADRC-based control system is robust and capable of rejecting disturbances, resulting in a significant reduction in the Total Harmonic Distortion (THD) of grid-connected currents. Comparative analysis with traditional control methods demonstrates the superior performance of the proposed approach.

Sleep quality mediates the effect of medical social support on depression symptoms in patients with HIV/AIDS.

OBJECTIVES: The purpose of our study is to further understanding of the depression symptoms of HIV/AIDS patients in Guilin, Guangxi via exploring whether there is a mediating effect of sleep quality on medical-social support and depression symptoms and therefore provide a theoretical basis for application of medical-social support to alleviate depression symptoms of HIV/AIDS patients. METHODS: A convenience sampling method was used to select 200 HIV/AIDS patients for the study. Depression symptoms, sleep quality, and medical-social support of the study participants were investigated using The Center for Epidemiological Studies Depression Scale (CES-D), The Pittsburg Sleep Quality Index (PSQI), and The Medical Outcomes Study Social Support Survey (MOS-SSS), respectively. Predictors of depression symptoms were explored by multiple linear regression, and Pearson correlation was used to analyze the relationship between sleep quality, medical-social support, and depression symptoms. Mediating effect analysis was performed by nonparametric Bootstrap test. RESULTS: In this study, the incidence of depression symptoms was 54.4%. Multiple linear regression analysis showed that leanness (ß = 0.161, P = 0.008), obesity (ß = 0.186, P = 0.002), sleep quality score > 7 (ß = 0.331, P < 0.001), and medical-social support score > 56 (ß = -0.247, P < 0.001) could influence depression symptoms of HIV and Pearson's correlation analysis demonstrated that there was a two-way correlation between sleep quality, medical social support and depression symptoms (P < 0.05). In addition, Bootstrap tests showed that medical-social support might affect depression symptoms not only directly but also indirectly through the mediating effect of sleep quality with the direct and mediating effects accounting for 77.25% and 22.75% of the total effect, respectively. CONCLUSION: The prevalence of depression symptoms is high among HIV/AIDS patients in Guilin City. The depressive symptoms of PLWHs(people living with HIV) are related to their sleep quality and medical-social support, and sleep quality partially mediates the relationship between medical-social support and depression symptoms. Therefore, interventions to improve sleep quality and medical-social support have the potential to allay the depression symptoms of HIV/AIDS patients.

P62 promotes FSH-induced antral follicle formation by directing degradation of ubiquitinated WT1.

In females, the pathophysiological mechanism of poor ovarian response (POR) is not fully understood. Considering the expression level of p62 was significantly reduced in the granulosa cells (GCs) of POR patients, this study focused on identifying the role of the selective autophagy receptor p62 in conducting the effect of follicle-stimulating hormone (FSH) on antral follicles (AFs) formation in female mice. The results showed that p62 in GCs was FSH responsive and that its level increased to a peak and then decreased time-dependently either in ovaries or in GCs after gonadotropin induction in vivo. GC-specific deletion of p62 resulted in subfertility, a significantly reduced number of AFs and irregular estrous cycles, which were same as pathophysiological symptom of POR. By conducting mass spectrum analysis, we found the ubiquitination of proteins was decreased, and autophagic flux was blocked in GCs. Specifically, the level of nonubiquitinated Wilms tumor 1 homolog (WT1), a transcription factor and negative controller of GC differentiation, increased steadily. Co-IP results showed that p62 deletion increased the level of ubiquitin-specific peptidase 5 (USP5), which blocked the ubiquitination of WT1. Furthermore, a joint analysis of RNA-seq and the spatial transcriptome sequencing data showed the expression of steroid metabolic genes and FSH receptors pivotal for GCs differentiation decreased unanimously. Accordingly, the accumulation of WT1 in GCs deficient of p62 decreased steroid hormone levels and reduced FSH responsiveness, while the availability of p62 in GCs simultaneously ensured the degradation of WT1 through the ubiquitin‒proteasome system and autophagolysosomal system. Therefore, p62 in GCs participates in GC differentiation and AF formation in FSH induction by dynamically controlling the degradation of WT1. The findings of the study contributes to further study the pathology of POR.

Multicomponent Synthesis of Imidazole-Based Ionizable Lipids for Highly Efficient and Spleen-Selective Messenger RNA Delivery.

The spleen emerges as a pivotal target for mRNA delivery, prompting a continual quest for specialized and efficient lipid nanoparticles (LNPs) designed to enhance spleen-selective transfection efficiency. Here we report imidazole-containing ionizable lipids (IMILs) that demonstrate a pronounced preference for mRNA delivery into the spleen with exceptional transfection efficiency. We optimized IMIL structures by constructing and screening a multidimensional IMIL library containing multiple heads, tails, and linkers to perform a structure-activity correlation analysis. Following high-throughput in vivo screening, we identified A3B7C2 as a top-performing IMIL in spleen-specific mRNA delivery via the formulated LNPs, achieving a remarkable 98% proportion of splenic transfection. Moreover, A3B7C2-based LNPs are particularly potent in splenic dendritic cell transfection. Comparative analyses revealed that A3B7C2-based LNPs achieved a notable 2.8-fold and 12.9-fold increase in splenic mRNA transfection compared to SM102 and DLin-MC3-DMA lipid formulations, respectively. Additionally, our approach yielded an 18.3-fold enhancement in splenic mRNA expression compared to the SORT method without introducing additional anionic lipids. Collectively, these IMILs highlight promising avenues for further research in spleen-selective mRNA delivery. This work offers valuable insights for the swift discovery and rational design of ionizable lipid candidates tailored for spleen-selective transfection, thereby facilitating the application of mRNA therapeutics in spleen-related interventions.

Pan-cancer transcriptional atlas of minimal residual disease links DUSP1 to chemotherapy persistence.

Chemotherapy is a commonly effective treatment for most types of cancer. However, many patients experience a relapse due to minimal residual disease (MRD) after chemotherapy. Previous studies have analyzed the changes induced by chemotherapy for specific types of cancer, but our study is the first to comprehensively analyze MRD across various types of cancer. We included both bulk and single-cell RNA sequencing datasets. We compared the expression of the entire genome and calculated scores for canonical pathway signatures and immune infiltrates before and after chemotherapy across different types of cancer. Our findings revealed that DUSP1 was the most significantly and widely enriched gene in pan-cancer MRD. DUSP1 was found to be essential for MRD formation and played a role in T cell-fibroblast communications and the cytotoxic function of CD4 + T cells. Overall, our analysis provides a comprehensive understanding of the changes caused by chemotherapy and identifies potential targets for preventing and eliminating MRD, which could lead to long-term survival benefits for patients.

Bayesian estimation of dissipation and sound speed in tube measurements using a transfer-function model.

This study discusses acoustic dissipation, which contributes to inaccuracies in impedance tube measurements. To improve the accuracy of these measurements, this paper introduces a transfer function model that integrates diverse dissipation prediction models. Bayesian inference is used to estimate the important parameters included in these models, describing dissipation originating from various mechanisms, sound speed, and microphone positions. By using experimental measurements and considering a hypothetical air layer in front of a rigid termination as the material under test, Bayesian parameter estimation allows a substantial enhancement in characterization accuracy by incorporating the dissipation and sound speed estimates. This approach effectively minimizes residual absorption coefficients attributed to both boundary-layer effects and air medium relaxation. The incorporation of dissipation models leads to a substantial reduction (to 1%) in residual absorption coefficients. Moreover, the use of accurately estimated parameters further enhances the accuracy of actual tube measurements of materials using the two-microphone transfer function method.

Tea-Derived Polyphenols Enhance Drought Resistance of Tea Plants (Camellia sinensis) by Alleviating Jasmonate-Isoleucine Pathway and Flavonoid Metabolism Flow.

Extreme drought weather has occurred frequently in recent years, resulting in serious yield loss in tea plantations. The study of drought in tea plantations is becoming more and more intensive, but there are fewer studies on drought-resistant measures applied in actual production. Therefore, in this study, we investigated the effect of exogenous tea polyphenols on the drought resistance of tea plant by pouring 100 mg·L-1 of exogenous tea polyphenols into the root under drought. The exogenous tea polyphenols were able to promote the closure of stomata and reduce water loss from leaves under drought stress. Drought-induced malondialdehyde (MDA) accumulation in tea leaves and roots was also significantly reduced by exogenous tea polyphenols. Combined transcriptomic and metabolomic analyses showed that exogenous tea polyphenols regulated the abnormal responses of photosynthetic and energy metabolism in leaves under drought conditions and alleviated sphingolipid metabolism, arginine metabolism, and glutathione metabolism in the root system, which enhanced the drought resistance of tea seedlings. Exogenous tea polyphenols induced jasmonic acid-isoleucine (JA-ILE) accumulation in the root system, and the jasmonic acid-isoleucine synthetase gene (TEA028623), jasmonic acid ZIM structural domain proteins (JAMs) synthesis genes (novel.22237, TEA001821), and the transcription factor MYC2 (TEA014288, TEA005840) were significantly up-regulated. Meanwhile, the flavonoid metabolic flow was significantly altered in the root; for example, the content of EGCG, ECG, and EGC was significantly increased. Thus, exogenous tea polyphenols enhance the drought resistance of tea plants through multiple pathways.

Polycomb repressive complex 1 modulates granulosa cell proliferation in early folliculogenesis to support female reproduction.

Rationale: Premature ovarian insufficiency (POI) is an accelerated reduction in ovarian function inducing infertility. Folliculogenesis defects have been reported to trigger POI as a consequence of ovulation failure. However, the underlying mechanisms remain unclear due to the genetic complexity and heterogeneity of POI. Methods: We used whole genome sequencing (WGS), conditional knockout mouse models combined with laser capture microdissection (LCM), and RNA/ChIP sequencing to analyze the crucial roles of polycomb repressive complex 1 (PRC1) in clinical POI and mammalian folliculogenesis. Results: A deletion mutation of MEL18, the key component of PRC1, was identified in a 17-year-old patient. However, deleting Mel18 in granulosa cells (GCs) did not induce infertility until its homolog, Bmi1, was deleted simultaneously. Double deficiency of BMI1/MEL18 eliminated PRC1 catalytic activity, upregulating cyclin-dependent kinase inhibitors (CDKIs) and thus blocking GC proliferation during primary-to-secondary follicle transition. This defect led to damaged intercellular crosstalk, eventually resulting in gonadotropin response failure and infertility. Conclusions: Our findings highlighted the pivotal role of PRC1 as an epigenetic regulator of gene transcription networks in GC proliferation during early folliculogenesis. In the future, a better understanding of molecular details of PRC1 structural and functional abnormalities may contribute to POI diagnosis and therapeutic options.

Modified R-BAC plus BTK inhibitor regimen in newly diagnosed young patients with mantle cell lymphoma: a real-world retrospective study.

To explore the optimal treatment for young patients with untreated mantle cell lymphoma (MCL), we compared the efficacy and safety of R-CHOP/R-DHAP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone/rituximab, dexamethasone, cytarabine and cisplatin) and R-BAP (rituximab, bendamustine, cytarabine, and prednisone) plus BTK (Bruton's tyrosine kinase) inhibitors in newly diagnosed patients. Eighty-three young patients (≤ 65 years old) with newly diagnosed MCL admitted to the First Affiliated Hospital of Zhengzhou University from January 1, 2014, to June 1, 2023, using R-CHOP/R-DHAP or R-BAP plus BTK inhibitor were assessed in this study. The median age at presentation was 60 (42-65) years in 83 patients, including 64 males and 19 females; 59 were treated with R-CHOP/R-DHAP regimen chemotherapy, and 24 were treated with R-BAP in combination with the BTK inhibitor regimen. The median follow-up was 17 months (2-86 months) in 83 patients, and the median PFS (progression-free survival) time was not reached. The CRR (complete response rate) of the R-BAP group was higher than that of the R-CHOP/R-DHAP group (87.5% vs. 54.2%, P = 0.005). The ORR (overall response rate) was not significantly different between the two groups (ORR: 91.7% vs. 84.7%, P = 0.497). The PFS (progression-free survival) of the R-BAP group was longer than that of the R-CHOP/R-DHAP group (P = 0.013), whereas OS was not significantly different between the two groups (P = 0.499). The most common adverse effect in both groups was hematotoxicity, with a higher incidence of grade 3-4 lymphopenia and grade 3-4 thrombocytopenia in the R-BAP group than in the R-CHOP/R-DHAP group (P = 0.015 and P = 0.039). Male sex (HR = 4.257, P = 0.013), LDH (lactate dehydrogenase) ≥ 245 U/L (HR = 3.221, P = 0.012), pleomorphic-blastoid (HR = 2.802, P = 0.043) and R-CHOP/R-DHAP regimen (HR = 7.704, P = 0.047) were independent risk factors for PFS. Ki67 ≥ 30% (HR = 8.539, P = 0.005) was an independent risk factor for OS. First-line treatment with R-BAP in combination with BTK inhibitor improved CRR and prolonged PFS in young patients with mantle cell lymphoma and adverse events were tolerable.

LSD1 promotes the FSH responsive follicle formation by regulating autophagy and repressing Wt1 in the granulosa cells.

In a growing follicle, the survival and maturation of the oocyte largely depend on support from somatic cells to facilitate FSH-induced mutual signaling and chemical communication. Although apoptosis and autophagy in somatic cells are involved in the process of FSH-induced follicular development, the underlying mechanisms require substantial study. According to our study, along with FSH-induced antral follicles (AFs) formation, both lysine-specific demethylase 1 (LSD1) protein levels and autophagy increased simultaneously in granulosa cells (GCs) in a time-dependent manner, we therefore evaluated the importance of LSD1 upon facilitating the formation of AFs correlated to autophagy in GCs. Conditional knockout of Lsd1 in GCs resulted in significantly decreased AF number and subfertility in females, accompanied by marked suppression of the autophagy in GCs. On the one hand, depletion of Lsd1 resulted in accumulation of Wilms tumor 1 homolog (WT1), at both the protein and mRNA levels. WT1 prevented the expression of FSH receptor (Fshr) in GCs and thus reduced the responsiveness of the secondary follicles to FSH induction. On the other hand, depletion of LSD1 resulted in suppressed level of autophagy by upregulation of ATG16L2 in GCs. We finally approved that LSD1 contributed to these sequential activities in GCs through its H3K4me2 demethylase activity. Therefore, the importance of LSD1 in GCs is attributable to its roles in both accelerating autophagy and suppressing WT1 expression to ensure the responsiveness of GCs to FSH during AFs formation.

[Efficacy and Prognosis of Chemotherapy Regimen Containing BTK Inhibitor in Treatment of Recurrent/Refractory Mantle Cell Lymphoma].

OBJECTIVE: To investigate the efficacy and prognosis of chemotherapy regimen containing Bruton's tyrosine kinase (BTK) inhibitor in the treatment of relapsed/refractory mantle cell lymphoma (R/R MCL). METHODS: The clinical data of 134 patients with R/R MCL were collected and analyzed retrospectively. The clinical characteristics of patients and effect of chemotherapy regimen on efficacy, overall survival (OS) and progression-free survival (PFS) were observed. RESULTS: The median age of the patients was 58(56-61) years old, and male to female ratio was about 2.9∶1. Patients with Ann Arbor stage III-IV accounted for 77.6%, extranodal involvement > 2 for 43.3%, bone marrow involvement for 60.4%, gastrointestinal involvement for 24.6%, and hepatosplenomegaly for 38.1%. The median follow-up time was 30 (2-103) months, overall response rate (ORR) was 41.8%, 3-year PFS was not reached, and 3-year and 5-year OS rate was 62.7% and 53.8%, respectively. The ORR of BTK inhibitor group was 56.9%, which was higher than 32.5% of non-BTK inhibitor group (P =0.006). The difference was statistically significant in PFS between the two groups (P =0.002), but was not in OS (P>0.05). The difference was statistically significant in OS between classical and special morphology (P < 0.001), but was not in PFS (P >0.05). Ki-67 was an influencing factor for OS and PFS. Multivariate analysis showed that Ki-67, B symptoms, MIPI score, and Ann Arbor stage were independent prognostic factors affecting patients' OS. The second-line treatment regimen was an independent prognostic factor affecting patients' PFS. CONCLUSIONS: The chemotherapy regimen containing BTK inhibitors can effectively improve the efficacy and prolong the PFS of R/R MCL patients. Ki-67, B symptoms, MIPI score, and Ann Arbor stage are independent prognostic factors for R/R MCL patients.

Disrupted small-world white matter networks in patients with major depression and recent suicide plans or attempts.

Suicide is a major concern for health, and depression is an established proximal risk factor for suicide. This study aimed to investigate white matter features associated with suicide. We constructed white matter structural networks by deterministic tractography via diffusion tensor imaging in 51 healthy controls, 47 depressed patients without suicide plans or attempts and 56 depressed patients with suicide plans or attempts. Then, graph theory analysis was used to measure global and nodal network properties. We found that local efficiency was decreased and path length was increased in suicidal depressed patients compared to healthy controls and non-suicidal depressed patients; moreover, the clustering coefficient was decreased in depressed patients compared to healthy controls; and the global efficiency and normalized characteristic path length was increased in suicidal depressed patients compared to healthy controls. Similarly, compared with those in non-suicidal depressed patients, nodal efficiency in the thalamus, caudate, medial orbitofrontal cortex, hippocampus, olfactory cortex, supplementary motor area and Rolandic operculum was decreased. In summary, compared with those of non-suicidal depressed patients, the structural connectome of suicidal depressed patients exhibited weakened integration and segregation and decreased nodal efficiency in the fronto-limbic-basal ganglia-thalamic circuitry. These alterations in the structural networks of depressed suicidal brains provide insights into the underlying neurobiology of brain features associated with suicide.

Transcription factor EB-mediated autophagy affects cell migration and inhibits apoptosis to promote endometriosis.

Autophagy has emerged as an important process of cell metabolism. With continuous in-depth research on autophagy, TFEB has been a key transcription factor regulating autophagy levels in recent years. Studies have established that TFEB regulates autophagy and apoptosis in various diseases. However, the relationship between TFEB and the pathogenesis of endometriosis remains unclear. This study aimed to investigate the effect of TFEB on the mechanism of endometriosis progression. The results showed that TFEB and autophagy-related protein LC3 are highly expressed in ectopic endometrium of patients with endometriosis, overexpression of TFEB in cultured human endometrial stromal cells (HESCs) by lentivirus not only promoted autophagy but also inhibited apoptosis. In addition, the migration and invasion ability of HESCs were enhanced by TFEB overexpression. Furthermore, inhibiting autophagy with specific inhibitors can attenuate migration and invasion of HESCs induced by TFEB. The rat models of endometriosis show that TFEB knockdown can suppress lesion growth in vivo. Our results suggest that autophagy may be involved in the progression mechanism of endometriosis, and the mechanism of autophagy disorder in endometriosis is probably related to TFEB. TFEB may be a key molecule in promoting endometriosis.

Unraveling the molecular mechanisms driving enhanced invasion capability of extravillous trophoblast cells: a comprehensive review.

Precise extravillous trophoblast (EVT) invasion is crucial for successful placentation and pregnancy. This review focuses on elucidating the mechanisms that promote heightened EVT invasion. We comprehensively summarize the pivotal roles of hormones, angiogenesis, hypoxia, stress, the extracellular matrix microenvironment, epithelial-to-mesenchymal transition (EMT), immunity, inflammation, programmed cell death, epigenetic modifications, and microbiota in facilitating EVT invasion. The molecular mechanisms underlying enhanced EVT invasion may provide valuable insights into potential pathogenic mechanisms associated with diseases characterized by excessive invasion, such as the placenta accreta spectrum (PAS), thereby offering novel perspectives for managing pregnancy complications related to deficient EVT invasion.

Wearable Sensors for Breath Monitoring Based on Water-Based Hexagonal Boron Nitride Inks Made with Supramolecular Functionalization.

Wearable humidity sensors are attracting strong attention as they allow for real-time and continuous monitoring of important physiological information by enabling activity tracking as well as air quality assessment. Amongst 2Dimensional (2D) materials, graphene oxide (GO) is very attractive for humidity sensing due to its tuneable surface chemistry, high surface area, processability in water, and easy integration onto flexible substrates. However, strong hysteresis, low sensitivity, and cross-sensitivity issues limit the use of GO in practical applications, where continuous monitoring is preferred. Herein, a wearable and wireless impedance-based humidity sensor made with pyrene-functionalized hexagonal boron nitride (h-BN) nanosheets is demonstrated. The device shows enhanced sensitivity towards relative humidity (RH) (>1010 Ohms/%RH in the range from 5% to 100% RH), fast response (0.1 ms), no appreciable hysteresis, and no cross-sensitivity with temperature in the range of 25-60 °C. The h-BN-based sensor is able to monitor the whole breathing cycle process of exhaling and inhaling, hence enabling to record in real-time the subtlest changes of respiratory signals associated with different daily activities as well as various symptoms of flu, without requiring any direct contact with the individual.

Channel Adaptive and Sparsity Personalized Federated Learning for Privacy Protection in Smart Healthcare Systems.

With the booming development of Smart Healthcare Systems (SHSs), employing federated learning (FL) in SHS devices has become a research hotspot. FL, as a distributed learning framework, can train models without sharing the original data among users, and then protect the user privacy. Existing research has proposed many methods to improve the security and efficiency of FL, which may not fully consider the characteristics of SHSs. Specifically, the requirements of privacy protection and efficiency pose significant challenges to FL. Current studies have struggled to balance privacy security and efficiency, and the degradation of model training efficiency in SHSs can be critical to patient health. Therefore, to improve the privacy protection of healthcare data and ensure communication efficiency, this work proposes a novel personalized FL framework based on Communication quality and Adaptive Sparsification (pFedCAS). In order to achieve privacy protection, a control unit is proposed and introduced to adjust the sparsity of the local model adaptively. To further improve the training efficiency, a selection unit is added during global model aggregation to select suitable clients for parameter updates. Finally, we validate the proposed method operated on the HAM10000 dataset. Simulation results validate that pFedCAS can not only improve privacy protection, but also gain an improvement of 15% in training accuracy and a reduction of 30% in training costs based on communication quality. The simulation results also validate the excellent robustness of pFedCAS to non-iid data.

Spatiotemporal trends of hemorrhagic fever with renal syndrome (HFRS) in China under climate variation.

Hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease caused by the rodent-transmitted orthohantaviruses (HVs), with China possessing the most cases globally. The virus hosts in China are Apodemus agrarius and Rattus norvegicus, and the disease spread is strongly influenced by global climate dynamics. To assess and predict the spatiotemporal trends of HFRS from 2005 to 2098, we collected historical HFRS data in mainland China (2005-2020), historical and projected climate and population data (2005-2098), and spatial variables including biotic, environmental, topographical, and socioeconomic. Spatiotemporal predictions and mapping were conducted under 27 scenarios incorporating multiple integrated representative concentration pathway models and population scenarios. We identify the type of magistral HVs host species as the best spatial division, including four region categories. Seven extreme climate indices associated with temperature and precipitation have been pinpointed as key factors affecting the trends of HFRS. Our predictions indicate that annual HFRS cases will increase significantly in 62 of 356 cities in mainland China. Rattus regions are predicted to be the most active, surpassing Apodemus and Mixed regions. Eighty cities are identified as at severe risk level for HFRS, each with over 50 reported cases annually, including 22 new cities primarily located in East China and Rattus regions after 2020, while 6 others develop new risk. Our results suggest that the risk of HFRS will remain high through the end of this century, with Rattus norvegicus being the most active host, and that extreme climate indices are significant risk factors. Our findings can inform evidence-based policymaking regarding future risk of HFRS.

The cGAS-STING pathway promotes the development of preeclampsia by upregulating autophagy: Mechanisms and implications.

OBJECTIVE: To investigate the influence and significance of cGAS-STING signaling pathway and autophagy on the occurrence and development of preeclampsia. DESIGN: A case-control experimental study, in vitro cell culture study, and in vivo animal research. METHODS: Human placenta tissue was collected and the differences in HE staining were observed. Immunohistochemistry and Western blot were used to verify differences in cGAS, STING and autophagy associated proteins. The PE rat model was established, the pathological changes of placenta and kidney were observed by HE staining, and the expression levels of related proteins were detected. In the lv-STING transfected HTR-8/SVneo trophoblast cell model, the expressions of autophagy indexes such as P62 and LC3 were verified by RT-PCR, Western blot and cell fluorescence experiments, and then the invasion and migration ability of cells were detected by Transwell and scrape tests. As an effective STING antagonist, C176 was administered to PE rats to observe whether it was effective in the treatment of PE disease. RESULTS: The expression levels of cGAS, STING and autophagy related proteins were increased in human and rat placental tissues. In the HTR-8/SVneo cell model which transfected by lv-STING, the expression levels of autophagy related indicators such as P62 and LC3 were increased. The invasion and migration ability of HTR-8/SVneo cells were significantly inhibited, which was improved by the autophagy inhibitor chloroquine. Acting as an effective STING antagonist in vivo, C176 significantly reversed the outcome of PE, alleviated and prevented the occurrence and development of PE. CONCLUSION: Our study proved that the cGAS-STING signaling pathway and autophagy levels are elevated in preeclampsia disease, and the cGAS-STING signaling pathway promotes the occurrence and development of preeclampsia through up-regulation of autophagy. This finding provides new insights into the pathogenesis of preeclampsia. Targeting this pathway may provide a potential therapeutic strategy for the treatment of preeclampsia.