An update on the role of ferroptosis in the pathogenesis of osteoporosis.

Ferroptosis is a novel form of programmed cell death, distinguished from apoptosis, autophagy, and programmed necrosis and has received much attention since it was defined in 2012. Ferroptotic cells physiologically exhibit iron metabolism dysregulation, oxidative stress, and lipid peroxidation. Morphologically, they show plasma membrane disruption, cytoplasmic swelling, and mitochondrial condensation. Osteoporosis is taken more and more seriously as the proportion of the aging population continues to increase globally. Interestingly, ferroptosis has been demonstrated to be involved in the development and progression of osteoporosis in many extant studies. The review summarizes iron metabolism, lipid peroxidation, and the different regulatory signals in ferroptosis. Changes in signaling mechanisms within osteoblasts, osteoclasts, and osteocytes after ferroptosis occur are explained here. Studies showed ferroptosis play an important role in different osteoporosis models (diabetes osteoporosis, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis). Inhibitors and EC (Exos) targeting ferroptosis could ameliorate bone loss in osteoporotic mice by protecting cells against lipid peroxidation. Shortly, we hope that more effective and appropriate clinical therapy means will be utilized in the treatment of osteoporosis.

Confined semiconducting polymers with boosted NIR light-triggered H2O2 production for hypoxia-tolerant persistent photodynamic therapy.

Hypoxia featured in malignant tumors and the short lifespan of photo-induced reactive oxygen species (ROS) are two major issues that limit the efficiency of photodynamic therapy (PDT) in oncotherapy. Developing efficient type-I photosensitizers with long-term ˙OH generation ability provides a possible solution. Herein, a semiconducting polymer-based photosensitizer PCPDTBT was found to generate 1O2, ˙OH, and H2O2 through type-I/II PDT paths. After encapsulation within a mesoporous silica matrix, the NIR-II fluorescence and ROS generation are enhanced by 3-4 times compared with the traditional phase transfer method, which can be attributed to the excited-state lifetime being prolonged by one order of magnitude, resulting from restricted nonradiative decay channels, as confirmed by femtosecond spectroscopy. Notably, H2O2 production reaches 15.8 µM min-1 under a 730 nm laser (80 mW cm-2). Further adsorption of Fe2+ ions on mesoporous silica not only improves the loading capacity of the chemotherapy drug doxorubicin but also triggers a Fenton reaction with photo-generated H2O2 in situ to produce ˙OH continuously after the termination of laser irradiation. Thus, semiconducting polymer-based nanocomposites enables NIR-II fluorescence imaging guided persistent PDT under hypoxic conditions. This work provides a promising paradigm to fabricate persistent photodynamic therapy platforms for hypoxia-tolerant phototheranostics.

Obesity and the obesity paradox in abdominal aortic aneurysm.

Obesity, characterized by its complexity and heterogeneity, has emerged as a significant public health concern. Its association with increased incidence and mortality of cardiovascular diseases stems not only from its complications and comorbidities but also from the endocrine effects of adipose tissue. Abdominal aortic aneurysm (AAA), a chronic inflammatory condition, has been closely linked to obesity. Intriguingly, mild obesity appears to confer a protective effect against AAA mortality, whereas severe obesity and being underweight do not, giving rise to the concept of the "obesity paradox". This review aims to provide an overview of obesity and its paradoxical relationship with AAA, elucidate its underlying mechanisms, and discuss the importance of preoperative weight loss in severely obese patients with AAA.

Oncogenic Gene CNOT7 Promotes Progression and Induces Poor Prognosis of Glioma.

Glioma is the most common malignant brain tumor in the central nervous system with the poor prognosis of patients. The CNOT7 (CCR4-NOT Transcription Complex Subunit 7) is an important functional subunit of CCR4-NOT protein complex that has not been reported in glioma. In this study, we aimed to explore the function of CNOT7 in glioma. The TCGA (The Cancer Genome Atlas) and CGGA (Chinese Glioma Genome Atlas) databases were used for investigating the expression and survival condition of CNOT7 in glioma. The cellular function experiments of qRT-PCR, CCK-8 assays, wound healing assays, and Transwell assays were conducted to verify the function of knockdown CNOT7 in the glioma cell lines DBTRG and U251. Enrichment analysis was used to explore the molecular mechanism of CONT7 in glioma. What is more, the upstream regulation transcription factors of CNOT7 were analyzed based on the ChIP-Atlas and cBioportal (provisional) databases, and verified by the qRT-PCR and luciferase reporter assay. The CNOT7 was highly expressed in glioma and presented the poorer prognosis. The knockdown of CNOT7 inhibited the proliferation, migration, and invasion of glioma cell line, compared to control group. The enrichment analysis revealed that the CNOT7 participated in the development of glioma via G2M checkpoint, E2F targets, IL6-JAK-STAT3, and TNF-α signaling pathways via NF-κB. Besides, it was found that the HDAC2 (Human histone deacetylase-2) contributes to increased CNOT7 expression in glioma. The high-expressed CNOT7 is an oncogene with poor prognosis and participate the progression of glioma.

Attenuated angiogenesis and macrophage infiltration during adipose tissue regeneration in a megavolume human fat grafting nude mouse model.

BACKGROUND: Survival and regeneration mechanisms of large (>250 mL) fat grafts remain incompletely understood. In fat grafts from volunteers with megavolume fat transfer breast augmentation, neovascularization and inflammatory cell infiltration decreased within 7 days according to histological analysis. We further investigated this phenomenon using a nude mouse model. METHODS: To simulate clinical contexts, chambers containing 1 mL human fat were implanted into nude mice. Chambers allowed selective transfer of tissue fluid from recipient nude mice into chambers, but not capillaries or macrophages. Seven days later, fat was removed from the chamber and reimplanted into a new nude mouse in the open-chambered fat group (OCFG, n=45). Adipose samples from volunteers and explanted grafts from OCFG were subjected to histological analyses. Graft weight, vascularization, and immune response were also compared between the OCFG and conventional direct fat grafting (control group (CG)). RESULTS: Percent tissue integrity, percent fibrosis, adipocyte viability, and neovascularization did not significantly differ between volunteer samples and OCFG grafts at day 7. On day 90, OCFG retention rate was decreased relative to CG and the fibrosis area was larger in the OCFG than in the CG. However, the macrophage and capillary counts were lower in the OCFG group relative to CG at days 7 and 14 after transplantation. CONCLUSIONS: The present study provides histological analyses of megavolume fat grafts sampled from clinical breast augmentation tissues and a xenograft nude mouse model. However, these preliminary results in a small clinical cohort should be further assessed in large allogeneic animal models.

Cleaner heating policies contribute significantly to health benefits and cost-savings: A case study in Beijing, China.

Cleaner heating policies aim to reduce air pollution and may bring about health benefits to individuals. Based on a fixed-effect model focusing on Beijing, this study found that after the onset of air pollution, daily clinic visits, hospitalization days, and hospitalization expenses increased several days after the occurrence of air pollution. These hospitalization changes were observed in males and females and three different age groups. A difference-in-differences (DID) model was constructed to identify the influences of cleaner heating policies on health consequences. The study revealed that the policy positively affects health outcomes, with an average decrease of 3.28 thousand clinic visits for all diseases. The total hospitalization days and expenses tend to decrease by 0.22 thousand days and 0.34 million CNY (Chinese Yuan), respectively. Furthermore, implementing the policy significantly reduced the number of daily clinic visits for respiratory diseases, asthma, stroke, diabetes, and chronic obstructive pulmonary diseases (COPDs).

Immunomodulation in diabetic wounds healing: The intersection of macrophage reprogramming and immunotherapeutic hydrogels.

Diabetic wound healing presents a significant clinical challenge due to the interplay of systemic metabolic disturbances and local inflammation, which hinder the healing process. Macrophages undergo a phenotypic shift from M1 to M2 during wound healing, a transition pivotal for effective tissue repair. However, in diabetic wounds, the microenvironment disrupts this phenotypic polarization, perpetuating inflammation, and impeding healing. Reprograming macrophages to restore their M2 phenotype offers a potential avenue for modulating the wound immune microenvironment and promoting healing. This review elucidates the mechanisms underlying impaired macrophage polarization toward the M2 phenotype in diabetic wounds and discusses novel strategies, including epigenetic and metabolic interventions, to promote macrophage conversion to M2. Hydrogels, with their hydrated 3D cross-linked structure, closely resemble the physiological extracellular matrix and offer advantageous properties such as biocompatibility, tunability, and versatility. These characteristics make hydrogels promising candidates for developing immunomodulatory materials aimed at addressing diabetic wounds. Understanding the role of hydrogels in immunotherapy, particularly in the context of macrophage reprograming, is essential for the development of advanced wound care solutions. This review also highlights recent advancements in immunotherapeutic hydrogels as a step toward precise and effective treatments for diabetic wounds.

Monovalent, bivalent and biparatopic nanobodies targeting S1 protein of porcine epidemic diarrhea virus efficiently neutralized the virus infectivity.

BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is a highly contagious coronavirus that causes severe diarrhea and death in neonatal piglets, which has brought huge economic losses to the pork industry worldwide since its first discovery in the early 1970s in Europe. Passive immunization with neutralizing antibodies against PEDV is an effective prevention measure. To date, there are no effective therapeutic drugs to treat the PEDV infection. RESULTS: We conducted a screening of specific nanobodies against the S1 protein from a phage display library obtained from immunized alpacas. Through competitive binding to antigenic epitopes, we selected instead of chose nanobodies with high affinity and constructed a multivalent tandem. These nanobodies were shown to inhibit PEDV infectivity by the neutralization assay. The antiviral capacity of nanobody was found to display a dose-dependent pattern, as demonstrated by IFA, TCID50, and qRT-PCR analyses. Notably, biparatopic nanobody SF-B exhibited superior antiviral activity. Nanobodies exhibited low cytotoxicity and high stability even under harsh temperature and pH conditions, demonstrating their potential practical applicability to animals. CONCLUSIONS: Nanobodies exhibit remarkable biological properties and antiviral effects, rendering them a promising candidate for the development of anti-PEDV drugs.

Lymphatic Vessel-Mediated Attenuation of Persistent Macrophage Infiltration Improves Fat Grafting Outcomes in Mice Models.

BACKGROUND: Persistent macrophage infiltration may lead to adverse consequences, such as calcifications and nodules in fat grafts. Lymphatic vessels, which transport inflammatory cells, are involved in regulating inflammatory responses. Less is known, however, about lymphatic vessels after fat grafting. OBJECTIVES: The aim of this study was to explore the regulation of fat graft survival by lymphatic vessels. METHODS: A common adipose graft model was constructed to assess the processes responsible for changes in the number of lymphatic vessels in grafts. Adipose tissue samples from C57/BL6 mice and green fluorescent protein-expressing mice were cross-grafted to determine the source of lymphatic vessels. The number of lymphatic vessels in the grafts was increased by treatment with vascular endothelial growth factor C, and the effects of this increase on fat grafting were evaluated. RESULTS: The number of lymphatic vessels was greater in postgrafted fat than in inguinal fat before transplantation, with lymphatic vessels in these grafts gradually transitioning from donor to recipient sources. Lymphatic vessels grew more slowly than blood vessels during early stages of grafting; during later stages, however, the number of blood vessels declined markedly, with more lymphatic vessels than blood vessels being observed 60 days after grafting. Vascular endothelial growth factor C treatment increased graft lymphatics and distant volume retention, while reducing fibrosis and oil sacs. Lymphatic vessels acted as drainage channels for macrophages, with the degree of sustained macrophage infiltration decreasing with increases in the number of lymphatic vessels. CONCLUSIONS: Increasing the number of lymphatic vessels is beneficial for fat graft survival, which may be related to a reduction in prolonged macrophage infiltration.

The browning and mobilization of subcutaneous white adipose tissue supports efficient skin repair.

Adipocytes in dermis are considered to be important participants in skin repair and regeneration, but the role of subcutaneous white adipose tissue (sWAT) in skin repair is poorly understood. Here, we revealed the dynamic changes of sWAT during wound healing process. Lineage-tracing mouse studies revealed that sWAT would enter into the large wound bed and participate in the formation of granulation tissue. Moreover, sWAT undergoes beiging after skin injury. Inhibition of sWAT beiging by genetically silencing PRDM16, a key regulator to beiging, hindered wound healing process. The transcriptomics results suggested that beige adipocytes in sWAT abundantly express neuregulin 4 (NRG4), which regulated macrophage polarization and the function of myofibroblasts. In diabetic wounds, the beiging of sWAT was significantly suppressed. Thus, adipocytes from sWAT regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes.

Erythrocyte Membrane Coating Alleviate Immune Response and Promoted Adipogenesis in Adipose Matrix.

Xenotransplantation of acellular adipose matrix (AAM) has come to prominence as an intriguing option for soft tissue reconstruction. However, the presence of immunogenic antigens within AAM can trigger unfavorable immune reactions, leading to inadequate in vivo regeneration outcomes. Therefore, the development of advanced technology capable of modulating immune responses is crucial for the therapeutic implementation of AAM xenografts. In this work, an innovative technique is created to bypass the immune system by covering the surface of both AAM and Arg-Gly-Asp (RGD) peptide-modified AAM xenografts with autologous red blood cell (RBC) membrane. The RBC membrane coating remained persistent and exhibited no significant decline even after 21 days. Moreover, it effectively reduced the expression of antigen major histocompatibility complex class 1 (MHC1) on the AAM surface. Following xenogeneic transplantation, the RBC-coated xenografts demonstrated increased expression of the adipogenic factor PPAR-γ, Adipoq, Fabp4, Fasn, and Plin1 and higher numbers of adipocytes. In addition, they exhibited decreased expression of immunological factors, including IL-6, IL-2, IFN-γ, and TNF-α, and fewer inflammatory cells. These findings indicate that RBC membrane coating successfully suppressed immune responses and promoted increased adipogenesis in AAM xenografts. Therefore, AAM camouflage coating with RBC has a lot of potential as a biomaterial for soft tissue reconstruction in clinical settings.

Plasmodium vivax serological exposure markers: PvMSP1-42-induced humoral and memory B-cell response generates long-lived antibodies.

Plasmodium vivax serological exposure markers (SEMs) have emerged as promising tools for the actionable surveillance and implementation of targeted interventions to accelerate malaria elimination. To determine the dynamic profiles of SEMs in current and past P. vivax infections, we screened and selected 11 P. vivax proteins from 210 putative proteins using protein arrays, with a set of serum samples obtained from patients with acute P. vivax and documented past P. vivax infections. Then we used a murine protein immune model to initially investigate the humoral and memory B cell response involved in the generation of long-lived antibodies. We show that of the 11 proteins, especially C-terminal 42-kDa region of P. vivax merozoite surface protein 1 (PvMSP1-42) induced longer-lasting long-lived antibodies, as these antibodies were detected in individuals infected with P. vivax in the 1960-1970s who were not re-infected until 2012. In addition, we provide a potential mechanism for the maintenance of long-lived antibodies after the induction of PvMSP1-42. The results indicate that PvMSP1-42 induces more CD73+CD80+ memory B cells (MBCs) compared to P. vivax GPI-anchored micronemal antigen (PvGAMA), allowing IgG anti-PvMSP1-42 antibodies to be maintained for a long time.

[Prognostic Significance of Progression of Disease within 24 Months in Mantle Cell Lymphoma].

OBJECTIVE: To investigate the effect of progression of disease within 24 months (POD24) on overall survival (OS) in patients with mantle cell lymphoma (MCL), and compare the clinical characteristics between POD24 and non-POD24 patients. METHODS: A retrospective analysis was performed on 50 MCL patients with treatment indications and regular treatment who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to August 2020. According to the occurrence of POD24, the patients were grouped for prognostic evaluation and clinical characteristics comparison. RESULTS: Univariate Cox regression analysis showed that POD24, PLT, albumin, MIPI score, ECOG PS score, LDH were the factors influencing OS in newly diagnosed MCL patients (all P < 0.05). The results of multivariate Cox regression analysis showed that POD24ï¼»HR=16.797(95%CI : 3.671-76.861),P < 0.001ï¼½, albumin<40 g/Lï¼»HR=3.238(95%CI :1.095-9.572),P =0.034ï¼½ and ECOG PS score≥2ï¼»HR=4.005(95%CI :1.033-15.521),P =0.045ï¼½ were independent risk factors influencing OS in MCL patients. The incidence of PLT<100×109/L (33.3% vs 5.9%, P =0.033) and ECOG PS score ≥2 (45.5% vs 5.9%, P =0.040) were significantly higher in POD24 patients than those in non-POD24 patients. CONCLUSION: POD24 is an independent poor prognostic factor affecting the OS of MCL patients, and the patients with PLT<100×109/L and ECOG PS score≥2 at diagnosis have a higher probability of POD24.

Aging and homeostasis of the hypodermis in the age-related deterioration of skin function.

Adipose tissues in the hypodermis, the crucial stem cell reservoir in the skin and the endocrine organ for the maintenance of skin homeostasis undergo significant changes during skin aging. Dermal white adipose tissue (dWAT) has recently been recognized as an important organ for both non-metabolic and metabolic health in skin regeneration and rejuvenation. Defective differentiation, adipogenesis, improper adipocytokine production, and immunological dissonance dysfunction in dWAT lead to age-associated clinical changes. Here, we review age-related alterations in dWAT across levels, emphasizing the mechanisms underlying the regulation of aging. We also discuss the pathogenic changes involved in age-related fat dysfunction and the unfavorable consequences of accelerated skin aging, such as chronic inflammaging, immunosenescence, delayed wound healing, and fibrosis. Research has shown that adipose aging is an early initiation event and a potential target for extending longevity. We believe that adipose tissues play an essential role in aging and form a potential therapeutic target for the treatment of age-related skin diseases. Further research is needed to improve our understanding of this phenomenon.

The Association between Short-Term Exposure to PM1 and Daily Hospital Admission and Related Expenditures in Beijing.

Ambient particulate matter (PM) pollution is a leading environmental health threat worldwide. PM with an aerodynamic diameter ≤ 1.0 µm, also known as PM1, has been implicated in the morbidity and mortality of several cardiorespiratory and cerebrovascular diseases. However, previous studies have mostly focused on analyzing fine PM (PM2.5) associated with disease metrics, such as emergency department visits and mortality, rather than ultrafine PM, including PM1. This study aimed to evaluate the association between short-term PM1 exposure and hospital admissions (HAs) for all-cause diseases, chronic obstructive pulmonary disease (COPD), and respiratory infections (RIs), as well as the associated expenditures, using Beijing as a case study. Here, based on air pollution and hospital admission data in Beijing from 2015 to 2017, we performed a time-series analysis and meta-analysis. It was found that a 10 µg/m3 increase in the PM1 concentration significantly increased all-cause disease HAs by 0.07% (95% Confidence Interval (CI): [0, 0.14%]) in Beijing between 2015 and 2017, while the COPD and RI-related HAs were not significantly associated with short-term PM1 exposure. Meanwhile, we estimated the attributable number of HAs and hospital expenditures related to all-cause diseases. This study revealed that an average of 6644 (95% CI: [351, 12,917]) cases of HAs were attributable to ambient PM1, which was estimated to be associated with a 106 million CNY increase in hospital expenditure annually (95% CI: [5.6, 207]), accounting for 0.32% (95% CI: [0.02, 0.62%]) of the annual total expenses. The findings reported here highlight the underlying impact of ambient PM pollution on health risks and economic burden to society and indicate the need for further policy actions on public health.

Rapid solar-driven atmospheric water-harvesting with MAF-4-derived nitrogen-doped nanoporous carbon.

Sorption-based atmospheric water-harvesting (AWH) could help to solve global freshwater scarcity. The search for adsorbents with high water-uptake capacity at low relative humidity, rapid adsorption-desorption kinetics and high thermal conductivity is a critical challenge in AWH. Herein, we report a MAF-4 (aka ZIF-8)-derived nanoporous carbon (NPCMAF-4-800) with multiple N-doped sites, considerable micropore characteristics and inherent photothermal properties, for efficient water production in a relatively arid climate. NPCMAF-4-800 exhibited optimal water-sorption performance of 306 mg g-1 at 40% relative humidity (RH). An excellent sunlight-absorption rate was realized (97%) attributed to its high degree of graphitization. A proof-of-concept device was designed and investigated for the practical harvesting of water from the atmosphere using natural sunlight. NPCMAF-4-800 achieved an unprecedentedly high water production rate of 380 mg g-1 h-1 at 40% RH, and could produce 1.77 L kg-1 freshwater during daylight hours in an outdoor low-humidity climate of ∼25 °C and 40% RH. These findings may shed light on the potential of MOF-derived porous carbons in the AWH field, and inspire the future development of solar-driven water-generation systems.

Railway track settlement patterns and control measures for multi-tunnel construction underneath a station track group: a case study.

This paper is based on the proximity engineering project of the Baishiyi tunnel group passing under the Chongqing West Station track group. Considering the train load and the spatial relationship of the tunnel and track groups, the settlement patterns, horizontal displacement, and differential settlement of the tunnel-strata-tracks system during the excavation process are studied through theoretical calculations and numerical simulation methods. The results indicate that the tunnel vault, strata, and track settlement deformation patterns are similar. Throughout the tunnel construction process, the tracks underwent uplift, settlement, and eventually stabilized. The settlement trough formed by the excavation of the three tunnels below the track group has an impact range of 25-145 m. Between 35 and 75 m, the differential settlement of the double track gradually increases with excavation. As the tunnel face reaches 75 m, the track differential settlement gradually converges and tends to stabilize. To minimize the impact of underpass tunnel construction on track groups, it is recommended to use a combination of full-section hole grouting and surface reinforcement grouting for ground reinforcement. Additionally, optimizing the construction parameters, including the step length and primary support closure time, and strengthening the locking anchor can further reduce the impact.

Innate lymphoid cell-based immunomodulatory hydrogel microspheres containing Cutibacterium acnes extracellular vesicles for the treatment of psoriasis.

Psoriasis is a chronic skin inflammation influenced by dysregulated skin microbiota, with the role of microbiota in psoriasis gaining increasing prominence. Bacterial extracellular vesicles (bEVs) serve as crucial regulators in the interaction between hosts and microbiota. However, the mechanism underlying the therapeutic potential of bEVs from commensal bacteria in psoriasis remains unclear. Here, we investigated the therapeutic role of Cutibacterium acnes (C. acnes)-derived extracellular vesicles (CA-EVs) in psoriasis treatment. To prolong the active duration of CA-EVs, we encapsulated them in gelatin methacrylate (GelMA) to fabricate hydrogel microspheres (CA-EVs@GHM) with sustained release properties. As GelMA degraded, CA-EVs were gradually released, maintaining a high concentration in mouse skin even 96 h post-treatment. In human keratinocyte cells (HaCaT), CA-EVs@GHM enhanced resistance to Staphylococcus aureus (S. aureus), promoted proliferation and migration of HaCaT cells exposed to S. aureus, and significantly reduced the expression of inflammatory genes such as interleukin (IL)-6 and C-X-C motif chemokine ligand 8 (CXCL8). In vivo, CA-EVs@GHM, more potent than CA-EVs alone, markedly attenuated proinflammatory gene expression, including tumor necrosis factor (TNF), Il6, Il17a, Il22 and Il23a in imiquimod (IMQ)-induced psoriasis-like mice, and restored skin barrier function. 16S rRNA sequencing revealed that CA-EVs@GHM might provide therapeutic effects against psoriasis by restoring microbiota diversity on the back skin of mice, reducing Staphylococcus colonization, and augmenting lipid metabolism. Furthermore, flow cytometry analysis showed that CA-EVs@GHM prevented the conversion of type 2 innate lymphoid cells (ILC2) to type 3 innate lymphoid cells (ILC3) in psoriasis-like mouse skin, reducing the pathogenic ILC3 population and suppressing the secretion of IL-17 and IL-22. In summary, our findings demonstrate that the long-term sustained release of CA-EVs alleviated psoriasis symptoms by controlling the transformation of innate lymphoid cells (ILCs) subgroups and restoring skin microbiota homeostasis, thus offering a promising therapy for psoriasis treatment. STATEMENT OF SIGNIFICANCE: Cutibacterium acnes, which is reduced in psoriasis skin, has been reported to promote skin homeostasis by regulating immune balance. Compared to live bacteria, bacterial extracellular vesicles (bEVs) are less prone to toxicity and safety concerns. bEVs play a pivotal role in maintaining bacterial homeostasis and modulating the immune system. However,bEVs without sustained release materials are unable to function continuously in chronic diseases. Therefore, we utilized hydrogel microspheres to encapsulate Cutibacterium acnes (C. acnes)-derived extracellular vesicles (CA-EVs), enabling long term sustained release. Our findings indicate that, CA-EVs loaded gelatin methacrylate hydrogel microspheres (CA-EVs@GHM) showed superior therapeutic effects in treating psoriasis compared to CA-EVs. CA-EVs@GHM exhibited a more significant regulation of pathological type 3 innate lymphoid cells (ILC3) and skin microbiota, providing a promising approach for microbiota-derived extracellular vesicle therapy in the treatment of skin inflammation.

Global climate change: Effects of future temperatures on emergency department visits for mental disorders in Beijing, China.

Rising temperatures can increase the risk of mental disorders. As climate change intensifies, the future disease burden due to mental disorders may be underestimated. Using data on the number of daily emergency department visits for mental disorders at 30 hospitals in Beijing, China during 2016-2018, the relationship between daily mean temperature and such visits was assessed using a quasi-Poisson model integrated with a distributed lag nonlinear model. Emergency department visits for mental disorders attributed to temperature changes were projected using 26 general circulation models under four climate change scenarios. Stratification analyses were then conducted by disease subtype, sex, and age. The results indicate that the temperature-related health burden from mental disorders was projected to increase consistently throughout the 21st century, mainly driven by high temperatures. The future temperature-related health burden was higher for patients with mental disorders due to the use of psychoactive substances and schizophrenia as well as for women and those aged <65 years. These findings enhance our knowledge of how climate change could affect mental well-being and can be used to advance and refine targeted approaches to mitigating and adapting to climate change with a view on addressing mental disorders.

Inhibition of Adipocyte Necroptosis Alleviates Fat Necrosis and Fibrosis After Grafting in a Murine Model.

BACKGROUND: Because of the delicate structure of the adipose tissue, fat necrosis accounts for 43.7% of all complications after autologous fat grafting; however, its regulation remains unclear. OBJECTIVES: The purpose of this study was to examine the role of necroptosis in fat graft remodeling after grafting. METHODS: Clinical fat graft necrosis samples were collected, and the expression levels of the necroptosis marker phosphorylated(p)-MLKL were analyzed. Transcriptome analysis was performed on fat grafts before and 1 week after transplantation in C57BL/6 mouse fat grafting models. Additionally, the in vivo effects of RIPK1 inhibitor Nec-1s or RIPK3 inhibitor GSK'872 on the fat grafting complications, including fat necrosis and fibrosis, were investigated. RESULTS: Necroptosis markers were observed and associated with higher occurrence of fibrosis in clinical fat graft necrosis samples compared to normal fat tissue. Amplification and RNA-Seq were conducted on RNA isolated from fat grafts before and after grafting. MLKL, RIPK1, and RIPK3's expression levels were significantly upregulated in comparison to controls. Higher expression levels of necroptotic RNAs were associated with higher levels of DAMPs, including Cxcl2, HMGB1, S100a8, S100a9, Nlrp3, and IL33, and activated proinflammatory signaling pathways, including the TNF, NF-kappa B, and chemokine signaling pathways. Necroptotic inhibitor Nec-1s and GSK'872 robustly suppressed the p-MLKL expression level and significantly inhibited necroptotic cell death, especially in adipocytes. Moreover, administration of Nec-1s and GSK'872 significantly alleviated fat necrosis and subsequent fibrosis in fat grafts. CONCLUSIONS: Collectively, our study findings highlight the potential therapeutic applications of necroptosis inhibitors in preventing fat necrosis and fibrosis after grafting.