Take vedolizumab home: transition from intravenous to subcutaneous treatment.

In 2020, the European Medicines Agency approved subcutaneous (SC) vedolizumab (VDZ) for the maintenance treatment of adult patients with moderate to severe inflammatory bowel disease (IBD). This article reviews the efficacy, safety, persistence, pharmacology, patient satisfaction, and economic implications of transitioning to SC VDZ treatment and explores whether SC formulations can be recommended by the same guidelines as intravenous (IV) formulations. Clinical trials and real-world evidence indicate that transitioning from IV to SC VDZ in patients with IBD maintains clinical, biochemical, and patient-reported clinical remission and is well-tolerated, with no new safety issues identified, except for injection site reactions. Moreover, SC VDZ has an exposure-response relationship and low immunogenicity, is economical, and provides a high level of patient satisfaction. Owing to these advantages, transitioning may be advisable. In the future, more studies are needed to clarify the exact role of SC VDZ in IBD treatment, including optimization and transitioning strategies and individualized treatments based on baseline characteristics.

Subcutaneous vedolizumab for inflammatory bowel disease Transitioning from intravenous to subcutaneous vedolizumab (SC VDZ) in patients with inflammatory bowel disease maintains clinical, biochemical, and patient-reported clinical remission and is well-tolerated, with no new safety issues identified, except for injection site reactions. Moreover, SC VDZ has an exposure-response relationship and low immunogenicity, is economical, and provides a high level of patient satisfaction. Owing to these advantages, transitioning may be advisable.

Bibliometric and visualized analysis of the applications of exosomes based drug delivery.

Exosomes, endogenous vesicles secreted by cells, possess unique properties like high biocompatibility, low immunogenicity, targeting ability, long half-life, and blood-brain barrier permeability. They serve as crucial intercellular communication vectors in physiological processes and disease occurrence. Our comprehensive analysis of exosome-based drug delivery research from 2013 to 2023 revealed 2,476 authors from 717 institutions across 33 countries. Keyword clustering identified five research areas: drug delivery, mesenchymal stem cells, cancer immunotherapy, targeting ligands, surface modifications, and macrophages. The combination of exosome drug delivery technology with a proven clinical model enables the precise targeting of tumors with chemotherapy or radiosensitising agents, as well as facilitating gene therapy. This bibliometric analysis aims to characterize the current state and advance the clinical application of exosome-based drug delivery systems.

Serofast status in syphilis: Pathogenesis to therapeutics.

Syphilis, a sexually transmitted infection caused by Treponema pallidum, has been experiencing a rise in prevalence in recent years. "Syphilis serofast" describes a unique serological reaction in patients with syphilis whose clinical symptoms have resolved following consistent anti-syphilitic therapy, but the non-Treponema pallidum antigen serologic test is still positive. Syphilis serofast is a risk factor for syphilis recurrence, neurosyphilis, and multisystem involvement. Considering the current lack of comprehensive knowledge about the epidemiological characteristics, pathogenesis, and therapies of syphilis serofast, we conducted an online search of research relating to syphilis serofast over the last twenty years. Previous research has shown that the pathogenesis of syphilis serofast is mainly related to clinical factors, immune factors, syphilis subtypes, and T.pallidum membrane protein repeat gene antigen. There are two distinct viewpoints on the treatment of serofast: no excessive treatment and active treatment. In addition, serofast patients also showed two clinical outcomes: syphilis recurrence and persistent serofast status. This article systematically reviews the related factors, treatment, and clinical outcomes of syphilis serofast, provides a theoretical basis for its research, diagnosis, and treatment, and helps clinicians develop a follow-up treatment management plan for syphilis serofast.

Realizing thermoelectric cooling and power generation in N-type PbS0.6Se0.4 via lattice plainification and interstitial doping.

Thermoelectrics have great potential for use in waste heat recovery to improve energy utilization. Moreover, serving as a solid-state heat pump, they have found practical application in cooling electronic products. Nevertheless, the scarcity of commercial Bi2Te3 raw materials has impeded the sustainable and widespread application of thermoelectric technology. In this study, we developed a low-cost and earth-abundant PbS compound with impressive thermoelectric performance. The optimized n-type PbS material achieved a record-high room temperature ZT of 0.64 in this system. Additionally, the first thermoelectric cooling device based on n-type PbS was fabricated, which exhibits a remarkable cooling temperature difference of ~36.9 K at room temperature. Meanwhile, the power generation efficiency of a single-leg device employing our n-type PbS material reaches ~8%, showing significant potential in harvesting waste heat into valuable electrical power. This study demonstrates the feasibility of sustainable n-type PbS as a viable alternative to commercial Bi2Te3, thereby extending the application of thermoelectrics.

Treponema pallidum recombinant protein Tp0768 enhances the ability of HUVECs to promote neutrophil chemotaxis through TLR2/ER stress signaling pathway.

Neutrophils are essential cells involved in inflammation. However, the specific mechanism of neutrophil chemotaxis induced by Treponema Pallidum (T. pallidum) remains unknow. In this study, human umbilical vein endothelial cells (HUVECs) were utilized as target cells to investigate the expression levels of chemokines when stimulated with different concentrations of Tp0768(also known as TpN44.5 or TmpA, a T. pallidum infection dependent antigen). The results indicated that Tp0768 treatment enhanced neutrophil chemotaxis in HUVECs, which was closely associated with the expression levels of CXCL1(C-X-C Motif Chemokine Ligand 1), CXCL2(C-X-C Motif Chemokine Ligand 2), and CXCL8(C-X-C Motif Chemokine Ligand 8, also known as interleukin-8). At the same time, the results show that Toll Like Receptor 2 (TLR2) signaling pathway is activated and endoplasmic reticulum stress (ER stress) occurs. Furthermore, the findings revealed that the use of protein kinase RNA-like endoplasmic reticulum kinase (PERK) and Immunoglobulin-Regulated Enhancer 1 (IRE1) inhibitors reduced the expression levels of CXCL1, CXCL2, and CXCL8. Additionally, inhibiting TLR2 significantly decreased the expression levels of ER stress-related proteins (PERK and IRE1), CXCL1, CXCL2, and CXCL8. Consequently, neutrophil chemotaxis was significantly inhibited after treatment with TLR2, PERK, and IRE1 inhibitors. These findings shed light on the role of Tp0768 in enhancing neutrophil chemotaxis in endothelial cells, providing a foundation for further exploration of syphilis pathogenesis and offering a new direction for the diagnosis and treatment of T. pallidum infection.

Systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio in patients with type 2 diabetes at different stages of diabetic retinopathy.

AIM: To investigate systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) levels in patients with type 2 diabetes at different stages of diabetic retinopathy (DR). METHODS: This retrospective study included 141 patients with type 2 diabetes mellitus (DM): 45 without diabetic retinopathy (NDR), 47 with non-proliferative diabetic retinopathy (NPDR), and 49 with proliferative diabetic retinopathy (PDR). Complete blood counts were obtained, and NLR, PLR, and SII were calculated. The study analysed the ability of inflammatory markers to predict DR using receiver operating characteristic (ROC) curves. The relationships between DR stages and SII, PLR, and NLP were assessed using multivariate logistic regression. RESULTS: The average NLR, PLR, and SII were higher in the PDR group than in the NPDR group (P=0.011, 0.043, 0.009, respectively); higher in the NPDR group than in the NDR group (P<0.001 for all); and higher in the PDR group than in the NDR group (P<0.001 for all). In the ROC curve analysis, the NLR, PLR, and SII were significant predictors of DR (P<0.001 for all). The highest area under the curve (AUC) was for the PLR (0.929 for PLR, 0.925 for SII, and 0.821 for NLR). Multivariate regression analysis indicated that NLR, PLR, and SII were statistically significantly positive and independent predictors for the DR stages in patients with DM [odds ratio (OR)=1.122, 95% confidence interval (CI): 0.200-2.043, P<0.05; OR=0.038, 95%CI: 0.018-0.058, P<0.05; OR=0.007, 95%CI: 0.001-0.01, P<0.05, respectively). CONCLUSION: The NLR, PLR, and SII may be used as predictors of DR.

Parenteral n-3 polyunsaturated fatty acids supplementation improves postoperative recovery for patients with Crohn's disease after bowel resection: a randomized, unblinded controlled clinical trial.

BACKGROUND: The postoperative inflammatory response is associated with postoperative recovery in surgery. n-3 (ω-3) polyunsaturated fatty acids have been reported to lower inflammation. The postoperative role of parenteral n-3 polyunsaturated fatty acids supplementation on outcomes in Crohn's disease after bowel resection is unclear. OBJECTIVES: We aimed to investigate the effects of postoperative parenteral n-3 polyunsaturated fatty acids supplementation in Crohn's disease. METHODS: A prospective randomized, unblinded controlled clinical trial was conducted for patients with Crohn's disease who underwent bowel resection between May 2019 and February 2022. Postoperative complications, complete blood count, serum biochemical values, and cytokine concentrations were compared in patients with and without parenteral n-3 polyunsaturated fatty acids supplementation for 5 d postoperatively. RESULTS: There were 268 patients randomly assigned in the analysis, with 134 in the control group (a mix of long-chain and medium-chain fats at 1.0 g/kg/d) and 134 in the treatment group (long-chain, medium-chain, and n-3 polyunsaturated fats at 1.2 g/kg/d). Twenty-six did not complete the allocated treatment, and 8 patients were lost to follow-up. The intention-to-treat analysis and the per-protocol analysis showed that there were a significant reduction in overall complication rates (22.4% compared with 49.3%; P < 0.001 and 21.8% compared with 38.2%; P = 0.006) and postoperative stay (8.8 ± 4.5 d compared with 11.2 ± 6.8 d; P = 0.001 and 8.7 ± 4.0 d compared with 11.5 ± 7.3 d; P < 0.001) in patients with parenteral n-3 polyunsaturated fatty acids supplementation compared with patients in the control group. In the secondary outcomes, the mean ± standard deviation of interleukin (IL)-6 (17.11 ± 2.14 pg/mL compared with 30.50 ± 5.14 pg/mL; P = 0.014), IL-1ß (2.01 ± 0.05 pg/mL compared with 2.24 ± 0.09 pg/mL; P = 0.019), tumor necrosis factor-α (2.09 ± 0.06 pg/mL compared with 2.29 ± 0.06 pg/mL; P = 0.029), and C-reactive protein concentrations (51.3 ± 4.2 mg/L compared with 64.4 ± 5.3 mg/L; P = 0.050) on postoperative day 5 in the treatment group were much lower than those in the control group. CONCLUSIONS: Parenteral n-3 polyunsaturated fatty acids supplementation promotes postoperative recovery in patients with Crohn's disease following bowel resection, with fewer complications and reduced inflammatory cytokines. This trial was registered at clinicaltrials.gov as NCT03901937 at https://classic. CLINICALTRIALS: gov/ct2/show/NCT03901937?term=NCT03901937&cond=Crohn+Disease&draw=2&rank=1.

High Carrier Mobility and Promising Thermoelectric Module Performance of N-Type PbSe Crystals.

The scarcity of Te hampers the widespread use of Bi2Te3-based thermoelectric modules. Here, the thermoelectric module potential of PbSe is investigated by improving its carrier mobility. Initially, large PbSe crystals are grown with the temperature gradient method to mitigate grain boundary effects on carrier transport. Subsequently, light doping with <1mole‰ halogens (Cl/Br/I) increases room-temperature carrier mobility to ~1600 cm2 V-1 s-1, achieved by reducing carrier concentration compared to traditional heavy doping. Crystal growth design and light doping enhance carrier mobility without affecting effective mass, resulting in a high power factor ~40 µW cm-1 K-2 in PbSe-Cl/Br/I crystals at 300 K. Additionally, Cl/Br/I doping reduces thermal conductivity and bipolar diffusion, leading to significantly lower thermal conductivity at high temperature. Enhanced carrier mobility and suppressed bipolar effect boost ZT values across the entire temperature range in n-type PbSe-Cl/Br/I crystals. Specifically, ZT values of PbSe-Br crystal reach ~0.6 at 300 K, ~1.2 at 773 K, and the average ZT (ZTave) reaches ~1.0 at 300-773 K. Ultimately, ~5.8% power generation efficiency in a PbSe single leg with a maximum temperature cooling difference of 40 K with 7-pair modules is achieved. These results indicate the potential for cost-effective and high-performance thermoelectric cooling modules based on PbSe.

Understanding the role of ursodeoxycholic acid and gut microbiome in non-alcoholic fatty liver disease: current evidence and perspectives.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, resulting in a huge medical burden worldwide. Accumulating evidence suggests that the gut microbiome and bile acids play pivotal roles during the development of NAFLD. Patients with NAFLD exhibit unique signatures of the intestinal microbiome marked by the priority of Gram-negative bacteria, decreased ratio of Firmicutes/Bacteroidetes (F/B), and increased Prevotella and Lachnospiraceae. The intestinal microbiota is involved in the metabolism of bile acids. Ursodeoxycholic acid (UDCA) is a key determinant in maintaining the dynamic communication between the host and gut microbiota. It generally shows surprising therapeutic potential in NAFLD with several mechanisms, such as improving cellular autophagy, apoptosis, and mitochondrial functions. This action is based on its direct or indirect effect, targeting the farnesoid X receptor (FXR) and various other nuclear receptors. This review aims to discuss the current studies on the involvement of the microbiome-UDCA interface in NAFLD therapy and provide prospective insights into future preventative and therapeutic approaches for NAFLD.

Realizing high-efficiency thermoelectric module by suppressing donor-like effect and improving preferred orientation in n-type Bi2(Te, Se)3.

Thermoelectric materials have a wide range of application because they can be directly used in refrigeration and power generation. And the Bi2Te3 stand out because of its excellent thermoelectric performance and are used in commercial thermoelectric devices. However, n-type Bi2Te3 has seriously hindered the development of Bi2Te3-based thermoelectric devices due to its weak mechanical properties and inferior thermoelectric performance. Therefore, it is urgent to develop a high-performance n-type Bi2Te3 polycrystalline. In this work, we employed interstitial Cu and the hot deformation process to optimize the thermoelectric properties of Bi2Te2.7Se0.3, and a high-performance thermoelectric module was fabricated based on this material. Our combined theoretical and experimental effort indicates that the interstitial Cu reduce the defect density in the matrix and suppresses the donor-like effect, leading to a lattice plainification effect in the material. In addition, the two-step hot deformation process significantly improves the preferred orientation of the material and boosts the mobility. As a result, a maximum ZT of 1.27 at 373 K and a remarkable high ZTave of 1.22 across the temperature range of 300-425 K are obtained. The thermoelectric generator (TEG, 7-pair) and thermoelectric cooling (TEC, 127-pair) modules were fabricated with our n-type textured Cu0.01Bi2Te2.7Se0.3 coupled with commercial p-type Bi2Te3. The TEC module demonstrates superior cooling efficiency compared with the commercial Bi2Te3 device, achieving a ΔT of 65 and 83.4 K when the hot end temperature at 300 and 350 K, respectively. In addition, the TEG module attains an impressive conversion efficiency of 6.5% at a ΔT of 225 K, which is almost the highest value among the reported Bi2Te3-based TEG modules.

Influence of cancer-directed surgery on the prognosis of liver metastases from gastric cancer

There are controversial about the application of cancer-directed surgery (CDS) in patients with liver metastases from gastric cancer, with improved responses to chemotherapy and targeted treatments, the role of CDS in metastatic gastric cancer to the liver needs to be revisited. This study aimed to evaluate the effect of CDS on patients with liver metastases from gastric cancer. Data for patients with liver metastases from gastric cancer were extracted from the population-based Surveillance, Epidemiology, and End Results (SEER) database. A total of 958 individuals were enrolled, 285 in the CDS group and 673 in the non-cancer guided surgery (Non-CDS) group. Following propensity score matching (PSM) analysis at 1:1 in the two groups,285 were included in the survival analysis for each group. Kaplan–Meier values and Cox proportional risk models were used to estimate the effect of CDS on patients' prognoses. Compared with the Non-CDS group, the CDS group significantly prolonged the median overall survival from 4 months (95% confidence interval [CI] 3–5) to 11 months (95% CI 8–12), p value < 0.001. Overall survival (OS) at 1 year was higher in the CDS group than in the Non-CDS group, at 44% (95 CI 38–50) and 25% (95 CI 20–30), respectively. OS at 3 years was also higher in the CDS group than in the Non-CDS group, at 24% (95 CI 19–29) and 6% (95 CI 3–9), respectively. Multivariate analysis showed that Non-CDS (hazard ratio[HR] = 2.26, 95% CI 1.88–2.72, p value < 0.001) was an adverse independent prognostic factor for patients (AU)

Primary pulmonary histiocytic sarcoma with high PD-L1 expression benefited from immunotherapy: A case report and bioinformatic analysis.

Histiocytic sarcoma is an aggressive haematopoietic malignancy accounting for less than 1% of haematolymphoid neoplasms with a diagnosis based on morphology and immunophenotype of tissue biopsies with a very poor prognosis. Here, we report a 45-year-old man who was diagnosed with primary pulmonary histiocytic sarcoma with systemic metastases, with partial remission (PR) treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy, but it relapsed soon after therapy above. Tests demonstrated that TMB was 21 Muts/Mb PD-L1 expression was 90% positive, and the disease has been well-controlled over 3 years using immune checkpoint inhibitors (nivolumab and pembrolizumab). Bioinformatic pan-cancer analysis verified that there was the highest genetic alteration frequency of PD-L1 in which amplification accounted for the majority of sarcoma tumour samples. Following that, we found that the genetic alteration of PD-L1 was associated with poor prognosis in sarcoma patients in terms of overall survival (OS) (p = 1.51 × 10-4 ), progress-free survival (PFS) (p = 4.90 × 10-2 ) and disease-specific survival (DSS) (p = 4.90 × 10-2 ). To our knowledge, this may be the first reported case with high PD-L1 expression in primary pulmonary histiocytic sarcoma who may benefit from immunotherapy such as nivolumab and pembrolizumab significantly and safely.

Lattice Plainification Leads to High Thermoelectric Performance of P-Type PbSe Crystals.

Thermoelectrics has applications in power generation and refrigeration. Since only commercial Bi2 Te3 has a low abundance Te, PbSe gets attention. This work enhances the near-room temperature performance of p-type PbSe through enhancing carrier mobility via lattice plainification. Composition controlled and Cu-doped p-type PbSe crystals are grown through physical vapor deposition. Results exhibit an enhanced carrier mobility ≈2578 cm2  V-1  s-1 for Pb0.996 Cu0.0004 Se. Microstructure characterization and density functional theory calculations verify the introduced Cu atoms filled Pb vacancies, realizing lattice plainification and enhancing the carrier mobility. The Pb0.996 Cu0.0004 Se sample achieves a power factor ≈42 µW cm-1  K-2 and a ZT ≈ 0.7 at 300 K. The average ZT of it reaches ≈0.9 (300-573 K), resulting in a single-leg power generation efficiency of 7.1% at temperature difference of 270 K, comparable to that of p-type commercial Bi2 Te3 . A 7-pairs device paired the p-type Pb0.996 Cu0.0004 Se with the n-type commercial Bi2 Te3 shows a maximum cooling temperature difference ≈42 K with the hot side at 300 K, ≈65% of that of the commercial Bi2 Te3 device. This work highlights the potential of p-type PbSe for power generation and refrigeration near room temperature and hope to inspire researchers on replacing commercial Bi2 Te3 .

All-SnTe-Based Thermoelectric Power Generation Enabled by Stepwise Optimization of n-Type SnTe.

The practical application of thermoelectric devices requires both high-performance n-type and p-type materials of the same system to avoid possible mismatches and improve device reliability. Currently, environmentally friendly SnTe thermoelectrics have witnessed extensive efforts to develop promising p-type transport, making it rather urgent to investigate the n-type counterparts with comparable performance. Herein, we develop a stepwise optimization strategy for improving the transport properties of n-type SnTe. First, we improve the n-type dopability of SnTe by PbSe alloying to narrow the band gap and obtain n-type transport in SnTe with halogen doping over the whole temperature range. Then, we introduce additional Pb atoms to compensate for the cationic vacancies in the SnTe-PbSe matrix, further enhancing the electron carrier concentration and electrical performance. Resultantly, the high-ranged thermoelectric performance of n-type SnTe is substantially optimized, achieving a peak ZT of ∼0.75 at 573 K with a high average ZT (ZTave) exceeding 0.5 from 300 to 823 K in the (SnTe0.98I0.02)0.6(Pb1.06Se)0.4 sample. Moreover, based on the performance optimization on n-type SnTe, for the first time, we fabricate an all-SnTe-based seven-pair thermoelectric device. This device can produce a maximum output power of ∼0.2 W and a conversion efficiency of ∼2.7% under a temperature difference of 350 K, demonstrating an important breakthrough for all-SnTe-based thermoelectric devices. Our research further illustrates the effectiveness and application potential of the environmentally friendly SnTe thermoelectrics for mid-temperature power generation.

Efficacy of probiotic supplementation and impact on fecal microbiota in patients with inflammatory bowel disease: a systematic review and meta-analysis of randomized controlled trials.

Context: Research regarding the treatment of inflammatory bowel disease (IBD) with probiotics has not yielded consistent results. OBJECTIVE: The aim of this meta-analysis was to evaluate the efficacy of probiotics supplementation in patients with IBD. DATA SOURCES: Randomized controlled trials (RCTs) evaluating the efficacy of probiotics in patients with IBD were searched in PubMed, the Google Scholar database, Web of Science, and CrossRef for the period July 2003 to June 2023. DATA EXTRACTION: The RCTs were extracted, independently by 2 authors, according to the PICOS criteria. DATA ANALYSIS: Seven studies, including a total of 795 patients, met the study criteria. Five end points were selected to evaluate the efficacy. Of these, 3 indicators showed a statistically significant difference in efficacy: C-reactive protein (odds ratio [OR]: -2.45, 95% confidence interval [CI]: -3.16, -1.73, P < .01), the number of fecal Bifidobacterium (OR: 3.37, 95% CI: 3.28, 3.47, P < .01), and Lactobacillus(OR: 2.00, 95% CI: 1.91, 2.09, P < .01). The other 2 indicators (disease activity for Crohn's disease and for ulcerative colitis) showed no statistically significant difference, while the OR reflected a positive correlation. CONCLUSION: Probiotics supplementation may have a positive effect on IBD by reducing clinical symptoms, reducing the serological inflammatory markers, and increasing favorable gut flora in patients with IBD. Additional RCTs are needed to evaluate the therapeutic effect of probiotics in IBD.

Fisetin alleviates cerebral ischemia/reperfusion injury by regulating Sirt1/Foxc1/Ubqln1 pathway-mediated proteostasis.

BACKGROUND: Cerebral ischemia/reperfusion injury (IRI) is pathologically associated with protein damage. The flavonoid fisetin has good therapeutic effects on cerebral IRI. However, the role of fisetin in regulating protein damage during cerebral IRI development remains unclear. This study investigated the pharmacological effects of fisetin on protein damage during cerebral IRI progression and defined the underlying mechanism of action. METHODS: In vivo and in vitro models of cerebral IRI were established by middle cerebral artery occlusion/reperfusion (MACO/R) and oxygen-glucose deprivation/reperfusion (OGD/R) treatment, respectively. Triphenyl tetrazolium chloride staining was performed to detect cerebral infarct size, and the modified neurologic severity score was used to examine neurological deficits. LDH activity and protein damage were assessed using kits. HT22 cell vitality and apoptosis were examined using CCK-8 assay and TUNEL staining, respectively. Interactions between Foxc1, Ubqln1, Sirt1, and Ezh2 were analyzed using CoIP, ChIP and/or dual-luciferase reporter gene assays. RESULTS: Fisetin alleviated protein damage and ubiquitinated protein aggregation and neuronal death caused by MCAO/R and OGD/R. Ubqln1 knockdown abrogated the inhibitory effect of fisetin on OGD/R-induced protein damage, ubiquitinated protein aggregation, and neuronal death in HT22 cells. Further experiments demonstrated that Foxc1 functions as a transcriptional activator of Ubqln1 and that Sirt1 promotes Foxc1 expression by deacetylating Ezh2 and inhibiting its activity. Furthermore, Sirt1 knockdown abrogated fisetin-mediated biological effects on OGD/R-treated HT22 cells. CONCLUSION: Fisetin improved proteostasis during cerebral IRI by regulating the Sirt1/Foxc1/Ubqln1 signaling axis. Our findings strongly suggest that fisetin-mediated inhibition of protein damage after ischemic stroke is a part of the mechanism through which fisetin is neuroprotective in cerebral IRI.

Macrophage: Hidden Criminal in Therapy Resistance.

BACKGROUND: Although substantial efforts have been made by researchers to develop drugs, a disappointing reality is that the emergence of drug resistance is an unavoidable reality for the majority of patients. In recent years, emerging evidence suggests a connection between drug resistance and immune dysregulation. SUMMARY: As a ubiquitously distributed, versatile innate immune cell, macrophages play essential roles in maintaining tissue homeostasis in a steady state. Nevertheless, it is becoming aware that macrophages undermine the action of therapeutic drugs across various disease types. Reprogramming macrophage function has been proven to be effective in restoring patient responsiveness to treatment. Herein, we comprehensively reviewed how macrophages respond to drugs and the mechanisms by which they contribute to treatment unresponsiveness in cancer, inflammatory diseases, and metabolic diseases. In addition, future prospects in macrophage-based combination therapy were discussed. KEY MESSAGES: Targeting macrophages is a promising strategy for overcoming drug resistance in immune disorders.

Progression of unfolded protein response and ferroptosis in angiogenesis.

Angiogenesis is the growth of new blood vessels on preexisting ones. It is the outcome of a multifactorial effect involving several cells, which can be brought on by different stress reactions.The accumulation of unfolded proteins in the endoplasmic reticulum occurs when cells are stressed due to environmental changes, where physical or chemical stimuli induce endoplasmic reticulum stress, thereby activating the unfolded protein response (UPR), a homeostasis response designed to re-establish protein balance. Ferroptosis is a planned death of lipid peroxidation and anomalies in metabolism that is dependent on iron. Large concentrations of iron ions accumulate there, along with high concentrations of lipid peroxides and reactive oxygen species, all of which can contribute to the development of several diseases. Through the production of growth factors, adhesion factors, and inflammatory factors that trigger the start of angiogenesis, both UPR and Ferroptosis can be implicated in angiogenesis.To set the stage for further research on angiogenesis, this work concentrated on the effects of Ferroptosis and UPR on angiogenesis, respectively.

A stochastic model of preventive maintenance strategies for wind turbine gearboxes considering the incomplete maintenance.

In contemporary large wind farms, the combination of condition-based maintenance (CBM) and time-based maintenance (TBM) has become a prevalent approach in preventive maintenance, which is an indispensable part to ensure the safe, stable and environmental operation of equipment. However, the utilization of an inappropriate maintenance strategy may result in over-maintenance or under-maintenance, leading to unstable equipment operation. Furthermore, the majority of preventive maintenance involves replacement maintenance, which may have adverse effects on the performance of wind turbines with excessive maintenance time. Therefore, this paper takes the gearbox as a case study to introduce the incomplete maintenance parameters into the failure rate function to establish a state model based on the stochastic differential equation (SDE) and describing the state change of incomplete maintenance. And then simulating the state model of the gearbox and the joint preventive maintenance strategy of TBM and CBM through examples, resulting the time-based incomplete maintenance (TBIM) is proposed based on the TBM and the incomplete maintenance, and a new joint preventive maintenance strategy incorporating TBIM and CBM is proposed. Through developing the decision-making process of the maintenance strategy to optimize the inappropriate maintenance which including over-maintenance and under-maintenance and simulating the optimized preventive maintenance strategy to compare with that of TBM and CBM and verify the superiority and effectiveness of the proposed maintenance method.

The interplay between autophagy and ferroptosis presents a novel conceptual therapeutic framework for neuroendocrine prostate cancer.

In American men, the incidence of prostate cancer (PC) is the highest among all types of cancer, making it the second leading cause of mortality associated with cancer. For advanced or metastatic PC, antiandrogen therapies are standard treatment options. The administration of these treatments unfortunately carries the potential risk of inducing neuroendocrine prostate cancer (NEPC). Neuroendocrine differentiation (NED) serves as a crucial indicator of prostate cancer development, encompassing various factors such as phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), Yes-associated protein 1 (YAP1), AMP-activated protein kinase (AMPK), miRNA. The processes of autophagy and ferroptosis (an iron-dependent form of programmed cell death) play pivotal roles in the regulation of various types of cancers. Clinical trials and preclinical investigations have been conducted on many signaling pathways during the development of NEPC, with the deepening of research, autophagy and ferroptosis appear to be the potential target for regulating NEPC. Due to the dual nature of autophagy and ferroptosis in cancer, gaining a deeper understanding of the developmental programs associated with achieving autophagy and ferroptosis may enhance risk stratification and treatment efficacy for patients with NEPC.