Low-Dose Naltrexone for Excoriation Disorder.

Excoriation (skin-picking) disorder (ED) is a condition characterized by the repeated compulsion to pick at the skin, causing physical trauma and psychiatric distress. Patients often desire to cease skin-picking behavior but are unable to do so. Multiple treatment modalities are effective for ED, including naltrexone. Previous reports of naltrexone for ED were at a high dose of 50 mg. The efficacy of low-dose naltrexone (LDN) at 4.5 mg in managing ED has not been reported. We present a case of a 51-year-old female with ED who was evaluated in the pain clinic for fibromyalgia management. Her medications included gabapentin 600 mg PO TID and a history of opioid prescription for diffuse pain. She was started on naltrexone 4.5 mg PO QD for the management of fibromyalgia. Three months later, the patient reported improvement in her skin-picking disorder, with a lessened compulsion to itch at her skin and improved healing of existing lesions. When the naltrexone was temporarily interrupted for an elective procedure, her lesions worsened. Her lesions improved after she resumed the medication. Thereby, this patient experienced a therapeutic benefit from naltrexone for her skin-picking disorder, as demonstrated by the temporal changes in her symptoms. To our knowledge, this is the first reported case of ED improving with LDN, as other cases utilized 50 mg. Though few clinical trials or systematic reviews recommend the use of naltrexone for EDs, our case supports trialing LDN in the appropriate context.

The Role of Dietary Intake of Live Microbes in the Association Between Leisure-Time Physical Activity and Depressive Symptoms: A Population-based Study.

Current research has shown promising associations between factors such as diet, total physical activity, and mental health outcomes, acknowledging the intricate interplay between these variables. However, the role of dietary intake of live microbes, coupled with leisure-time physical activity (LTPA), in their relationship to depressive symptoms necessitates further exploration. The present study examined a cohort of 25,747 individuals who participated in the NHANES between the years 2007 and 2018. Patient's Health Questionnaire (PHQ-9) was employed, whereby individuals scoring ≥ 10 were classified as exhibiting symptoms of depression. LTPA status was reported by the Global Physical Activity Questionnaire and calculated by MET-minutes/week. Foods consumed by participants were evaluated by live microbes per gram, which were categorized into three groups: low, medium, and high. After controlling for all covariates, findings indicated that LTPA was negatively associated with depressive symptoms [OR (95% CI): 0.983(0.976,0.990), p < 0.001]. Participating in more LTPA was positively correlated with consuming all three levels of dietary live microbes [low, ß (95% CI): 0.086(0.063, 0.109); medium, ß (95% CI): 0.009(0.007, 0.012); high, ß (95% CI): 0.002(0.001, 0.002)]. Moreover, taking more foods with medium live microbes was associated with lower depressive likelihood [OR (95% CI): 0.931(0.882,0.982), p = 0.010]. Intake of medium and high levels of live microbes mediated the association between LTPA and depressive symptoms by 4.15 % and 0.83 %, respectively. Dietary intake of foods containing medium and high levels of live microbes may be a mediator of LTPA's negative association with depressive symptoms.

Impact of social support on the resilience of youth: mediating effects of coping styles.

Background: Chinese youth are at high risk for depression with a significantly higher detection rate of depression risk than other age groups, which brings about a huge challenge to the mental health work of universities. Developing supportive resources that promote resilience against adverse environmental influences in high-risk groups is quite more urgent than medical treatment for firm diagnoses of mental issues that have developed into depression in the current background. Methods: A total of 665 university students in China completed self-reported questionnaires measuring psychological resilience, social support, and coping styles. The structural equation model testing on the goodness of fit of the theoretical framework was first performed. Descriptive statistics and Pearson's correlation analysis among social support, resilience, and coping styles were then conducted. At last, we tested the mediating role of coping styles. Results: Social support has a significant positive effect on the psychological resilience of the youth. Mixed coping and immature coping styles have significant negative impacts on both social support and resilience, while mature coping styles have a significant positive effect on social support and resilience. Mature and immature coping styles mediate the association between social support and resilience in youth. Conclusion: Based on stress theory, this study explores mechanisms that facilitate the development of resilience in young people with regard to social support and coping styles. The current research depicts an interventional perspective of building a social support network that guides the youth to adopt mature coping styles to enhance their resilience and facilitate their mental health.

MiR-339-5p Inhibits Ferroptosis by Promoting Autophagic Degradation of FTH1 Through Targeting ATG7 in Liver Cancer Cells.

Background: Liver cancer has a high incidence and mortality rate worldwide, and there is an urgent need to identify new therapeutic strategies and predictive targets to improve the clinical outcomes of advanced liver cancer. Ferroptosis holds promise as a novel strategy for cancer therapy. Epigenetic dysregulation is a hallmark of cancer, and noncoding RNAs are tightly involved in cell fate determination. Therefore, we aimed to identify a novel ferroptosis regulator from aberrantly expressed microRNAs that may serve as a novel biomarker and therapeutic target for liver cancer. Methods: The expression signature and prognostic value of miR-339 was assessed using TCGA data set. The role of miR-339/ATG7/FTH1 axis in liver cancer cells were evaluated through growth curve, colony formation, 7-AAD staining. The role of miR-339 in regulation of ferroptosis was determined by immunofluorescence staining, flow cytometry, and Elisa kits. Results: Here, we showed that miR-339 is aberrantly overexpressed in patients with liver cancer. In addition, miR-339 inhibition dramatically suppresses liver cancer progression. Furthermore, miR-339 silencing drives cell death and inhibits liver cancer progression, indicating that miR-339 may serve as a novel ferroptosis suppressor. Mechanistically, we demonstrated that miR-339 targets ATG7 to facilitate the autophagic degradation of FTH1 and prevent ferroptosis in liver cancer cells. Conclusions: We provide important evidence that the miR-339 inhibition activates of the autophagy pathway to promote ferroptosis by degrading FTH1 in liver cancer cells. We found that miR-339 regulates the balance between ferroptosis and autophagy in liver cancer cells.

Clinical outcomes of treatment-naïve HBeAg-negative patients with chronic hepatitis B virus infection with low serum HBsAg and undetectable HBV DNA.

Serum hepatitis B surface antigen (HBsAg) level < 100 IU/ml and undetectable hepatitis B virus (HBV) DNA have been recently proposed as an alternate endpoint of "partial cure" in chronic hepatitis B (CHB). We investigated clinical outcomes of hepatitis B e antigen (HBeAg)-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA. Treatment-naïve HBeAg-negative CHB patients with undetectable HBV DNA and normal alanine aminotransferase were retrospectively included from three institutions. Patients were classified into the low HBsAg group (<100 IU/ml) and the high HBsAg group (≥100 IU/ml). Liver fibrosis was evaluated by noninvasive tests (NITs). A total of 1218 patients were included and the median age was 41.5 years. Patients with low HBsAg were older (45.0 vs. 40.0 years, P < 0.001) than those in the high HBsAg group, while the NIT parameters were comparable between groups. During a median follow-up of 25.7 months, patients with low HBsAg achieved a higher HBsAg clearance rate (13.0% vs. 0%, P < 0.001) and a lower rate of significant fibrosis development (2.2% vs. 7.0%, P = 0.049) compared to patients with high HBsAg. No patient developed HCC in either group. HBsAg level was negatively associated with HBsAg clearance (HR 0.213, P < 0.001) and patients with HBsAg < 100 IU/ml had a low risk of significant fibrosis development (HR 0.010, P = 0.002). The optimal cutoff value of HBsAg for predicting HBsAg clearance was 1.1 Log10 IU/ml. Treatment-naïve HBeAg-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA had favourable outcomes with a high rate of HBsAg clearance and a low risk of fibrosis progression.

Nomograms for predicting prognostic value of combined neutrophil-to-lymphocyte ratio and SCC-Ag in locally advanced cervical cancer.

Background: Accumulating evidence supports the important role of inflammation in tumorigenesis and progression. Squamous cell carcinoma-associated antigen (SCC-Ag) is a tumor marker widely used to predict the prognosis of patients with cervical squamous cell carcinoma. This paper explored the predictive value of combined detection of neutrophil-to-lymphocyte ratio (NLR) to SCC-Ag for prognosis in patients with locally advanced cervical cancer (LACC). Methods: A retrospective analysis was conducted on 190 LACC patients who underwent concurrent chemoradiotherapy (CCRT) from January 2012 to December 2016. NLR and SCC-Ag were analyzed before treatment. Receiver operating characteristic (ROC) curve analysis was employed to determine the optimal cutoff point for NLR and SCC-Ag. Kaplan-Meier analysis and Cox regression analysis were performed to assess their prognostic values. Nomograms were established to predict progression-free survival (PFS) and overall survival (OS), and the Harrell's concordance index (C-index) was introduced to evaluate the accuracy of predictions. Results: The optimal cutoff values for SCC-Ag and NLR were 3.25 ng/mL and 2.52, respectively. Patients with SCC-Ag >3.25 ng/mL and NLR >2.52 were significantly associated with decreased PFS and OS. Multivariate analysis indicated that SCC-Ag and NLR were independent prognostic factors for PFS (P=0.022 and P=0.004, respectively) and OS (P=0.031 and P=0.001, respectively). The area under the curve of SCC-Ag, NLR and their combination to predict PFS and OS of LACC were 0.688, 0.623, 0.708 and 0.684, 0.658, 0.723, respectively. C-index of nomograms based on PFS and OS were 0.725 [95% confidence interval (CI): 0.653-0.797] and 0.731 (95% CI: 0.658-0.804), respectively. Conclusions: The combination of SCC-Ag and NLR could provide a better predictive prognosis than SCC-Ag or NLR alone, and nomograms based on PFS and OS can be recommended as practical models for evaluating the prognosis of LACC patients.

Modulators for palmitoylation of proteins and small molecules.

As an essential form of lipid modification for maintaining vital cellular functions, palmitoylation plays an important role in in the regulation of various physiological processes, serving as a promising therapeutic target for diseases like cancer and neurological disorders. Ongoing research has revealed that palmitoylation can be categorized into three distinct types: N-palmitoylation, O-palmitoylation and S-palmitoylation. Herein this paper provides an overview of the regulatory enzymes involved in palmitoylation, including palmitoyltransferases and depalmitoylases, and discusses the currently available broad-spectrum and selective inhibitors for these enzymes.

Neoadjuvant chemo-immunotherapy with camrelizumab plus nab-paclitaxel and cisplatin in resectable locally advanced squamous cell carcinoma of the head and neck: a pilot phase II trial.

Neoadjuvant chemoimmunotherapy has emerged as a potential treatment option for resectable head and neck squamous cell carcinoma (HNSCC). In this single-arm phase II trial (NCT04826679), patients with resectable locally advanced HNSCC (T2‒T4, N0‒N3b, M0) received neoadjuvant chemoimmunotherapy with camrelizumab (200 mg), nab-paclitaxel (260 mg/m2), and cisplatin (60 mg/m2) intravenously on day one of each three-week cycle for three cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included pathologic complete response (pCR), major pathologic response (MPR), two-year progression-free survival rate, two-year overall survival rate, and toxicities. Here, we report the perioperative outcomes; survival outcomes were not mature at the time of data analysis. Between April 19, 2021 and March 17, 2022, 48 patients were enrolled and received neoadjuvant therapy, 27 of whom proceeded to surgical resection and remaining 21 received non-surgical therapy. The ORR was 89.6% (95% CI: 80.9, 98.2) among 48 patients who completed neoadjuvant therapy. Of the 27 patients who underwent surgery, 17 (63.0%, 95% CI: 44.7, 81.2) achieved a MPR or pCR, with a pCR rate of 55.6% (95% CI: 36.8, 74.3). Treatment-related adverse events of grade 3 or 4 occurred in two patients. This study meets the primary endpoint showing potential efficacy of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin, with an acceptable safety profile, in patients with resectable locally advanced HNSCC.

Size selection of intrahepatic lesions for cryoablation contributes to abscopal effect and long-term survival in patients with liver metastatic melanoma receiving PD-1 blockade therapy.

OBJECTIVES: In this study, we aimed to examine parameters of cryoablation, tumor characteristics, and their correlations with distant tumor response and survival of liver metastatic melanoma patients receiving cryoablation and PD-1 blockade (cryo-PD-1) combination treatment. MATERIALS AND METHODS: A retrospective study was conducted among 45 melanoma patients who received combined PD-1 blockade therapy and cryoablation for liver metastasis from 2018 to 2022. Cox regression was utilized to determine the associations between factors and overall survival (OS). Changes in cytokines and immune cell compositions in peripheral blood samples following the combined treatment were investigated, along with their correlations with treatment response. RESULTS: The mean cycle of cryo-PD-1 combination treatment was 2.2 (range, 1-6), and the 3-month overall response rate (RECIST 1.1 criteria) was 26.7%. Of the 21 patients who failed previous PD-1 blockade therapy after diagnosis of liver metastasis, 4 (19.0%) achieved response within 3 months since combination treatment. The diameter of ablated lesion ≤ 30 mm, metastatic organs ≤ 2, and pre-treatment LDH level ≤ 300 U/L were independent prognostic factors for favorable OS. Further analysis showed patients with intrahepatic tumor size of 15-45 mm, and ablated lesion size of ≤ 30 mm had significantly higher 3-month response rate (42.9% vs 12.5%; P = 0.022) and survival time (30.5 vs 14.2 months; P = 0.045) than their counterparts. The average increase in NLR among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 3.59 ± 5.01 and 7.21 ± 12.57, respectively. The average increase in serum IL-6 levels among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 8.62 ± 7.95 pg/ml and 15.40 ± 11.43 pg/ml, respectively. CONCLUSION: Size selection of intrahepatic lesions for cryoablation is important in order to achieve abscopal effect and long-term survival among patients with liver metastatic melanoma receiving PD-1 blockade therapy.

Bile acids modified by the intestinal microbiota promote colorectal cancer growth by suppressing CD8+ T cell effector functions.

Concentrations of the secondary bile acid, deoxycholic acid (DCA), are aberrantly elevated in colorectal cancer (CRC) patients, but the consequences remain poorly understood. Here, we screened a library of gut microbiota-derived metabolites and identified DCA as a negative regulator for CD8+ T cell effector function. Mechanistically, DCA suppressed CD8+ T cell responses by targeting plasma membrane Ca2+ ATPase (PMCA) to inhibit Ca2+-nuclear factor of activated T cells (NFAT)2 signaling. In CRC patients, CD8+ T cell effector function negatively correlated with both DCA concentration and expression of a bacterial DCA biosynthetic gene. Bacteria harboring DCA biosynthetic genes suppressed CD8+ T cells effector function and promoted tumor growth in mice. This effect was abolished by disrupting bile acid metabolism via bile acid chelation, genetic ablation of bacterial DCA biosynthetic pathway, or specific bacteriophage. Our study demonstrated causation between microbial DCA metabolism and anti-tumor CD8+ T cell response in CRC, suggesting potential directions for anti-tumor therapy.

Inhibition the ubiquitination of ENaC and Na,K-ATPase with erythropoietin promotes alveolar fluid clearance in sepsis-induced acute respiratory distress syndrome.

Sepsis-induced acute respiratory distress syndrome (ARDS) causes significant fatalities worldwide and lacks pharmacological intervention. Alveolar fluid clearance (AFC) plays a pivotal role in the remission of ARDS and is markedly impaired in the pathogenesis of ARDS. Here, we demonstrated that erythropoietin could effectively ameliorate lung injury manifestations and lethality, restore lung function and promote AFC in a rat model of lipopolysaccharide (LPS)-induced ARDS. Moreover, it was proven that EPO-induced restoration of AFC occurs through triggering the total protein expression of ENaC and Na,K-ATPase channels, enhancing their protein abundance in the membrane, and suppressing their ubiquitination for degeneration. Mechanistically, the data indicated the possible involvement of EPOR/JAK2/STAT3/SGK1/Nedd4-2 signaling in this process, and the pharmacological inhibition of the pathway markedly eliminated the stimulating effects of EPO on ENaC and Na,K-ATPase, and subsequently reversed the augmentation of AFC by EPO. Consistently, in vitro studies of alveolar epithelial cells paralleled with that EPO upregulated the expression of ENaC and Na,K-ATPase, and patch-clamp studies further demonstrated that EPO substantially strengthened sodium ion currents. Collectively, EPO could effectively promote AFC by improving ENaC and Na,K-ATPase protein expression and abundance in the membrane, dependent on inhibition of ENaC and Na,K-ATPase ubiquitination, and resulting in diminishing LPS-associated lung injuries.

Anchoring Active Li Metal in Oriented Channel by In Situ Formed Nucleation Sites Enabling Durable Lithium-Metal Batteries.

Lithium metal is the ultimate anode material for pursuing the increased energy density of rechargeable batteries. However, fatal dendrites growth and huge volume change seriously hinder the practical application of lithium metal batteries (LMBs). In this work, a lithium host that preinstalled CoSe nanoparticles on vertical carbon vascular tissues (VCVT/CoSe) is designed and fabricated to resolve these issues, which provides sufficient Li plating space with a robust framework, enabling dendrite-free Li deposition. Their inherent N sites coupled with the in situ formed lithiophilic Co sites loaded at the interface of VCVT not only anchor the initial Li nucleation seeds but also accelerate the Li+ transport kinetics. Meanwhile, the Li2 Se originated from the CoSe conversion contributes to constructing a stable solid-electrolyte interphase with high ionic conductivity. This optimized Li/VCVT/CoSe composite anode exhibits a prominent long-term cycling stability over 3000 h with a high areal capacity of 10 mAh cm-2 . When paired with a commercial nickel-rich LiNi0.83 Co0.12 Mn0.05 O2 cathode, the full-cell presents substantially enhanced cycling performance with 81.7% capacity retention after 300 cycles at 0.2 C. Thus, this work reveals the critical role of guiding Li deposition behavior to maintain homogeneous Li morphology and pave the way to stable LMBs.

Gasless robot-assisted transaxillary hemithyroidectomy (RATH): learning curve and complications.

PURPOSE: Gasless robot-assisted transaxillary hemithyroidectomy (RATH) is regarded as an alternative surgical option for thyroid operations. However, the associated steep learning curve is a clinical concern. This study evaluated the learning curve of RATH for surgeons without experience of endoscopic surgery and the early surgical outcomes of RATH. METHODS: We conducted a retrospective study of patients who underwent gasless RATH and conventional hemithyroidectomy (CH) at Sun Yat-sen University Cancer Center, Guangzhou, China, from June 2021 to August 2022. The learning curve and early surgical outcomes of gasless RATH were evaluated. And the early surgical outcomes of gasless RATH were compared to CH. RESULTS: In total, 105 patients who underwent gasless RATH and 104 patients who underwent CH were matched and assessed. The cumulative sum techniques (CUSUM) analysis showed that the peak point of gasless RATH operative time occurred at the 31st case. No clear single peak was identified in the CUSUM plot for drainage amount and blood loss. No significant difference in perioperative complications was observed between these two groups. Moreover, the number of postoperative patients who got sense of thyroid area traction were fewer in the gasless RATH group (n = 11, 10.5%) than in the CH group (n = 32, 30.8%). CONCLUSION: Gasless RATH can be considered as an alternative approach to the conventional open procedure, as it is an easy remote access technique, with shorter learning curves and certain advantage such as less sense of thyroid area traction.

Who can benefit from postmastectomy radiotherapy among HR+/HER2- T1-2 N1M0 breast cancer patients? An explainable machine learning mortality prediction based approach.

Objective: The necessity of postmastectomy radiotherapy(PMRT) for patients with HR+/HER2 T1-2 N1M0 breast cancer remains controversial. We want to use explainable machine learning to learn the feature importance of the patients and identify the subgroup of the patients who may benefit from the PMRT. Additionally, develop tools to provide guidance to the doctors. Methods: In this study, we trained and validated 2 machine learning survival models: deep learning neural network and Cox proportional hazard model. The training dataset consisted of 35,347 patients with HR+/HER2- T1-2 N1M0 breast cancer who received mastectomies from the SEER database from 2013 to 2018. The performance of survival models were assessed using a concordance index (c-index).Then we did subgroup analysis to identify the subgroup who could benefit from PMRT. We also analyzed the global feature importance for the model and individual feature importance for individual survival prediction. Finally, we developed a Cloud-based recommendation system for PMRT to visualize the survival curve of each treatment plan and deployed it on the Internet. Results: A total of 35,347 patients were included in this study. We identified that radiotherapy improved the OS in patients with tumor size >14mm and age older than 54: 5-year OS rates of 91.9 versus 87.2% (radio vs. nonradio, P <0.001) and cohort with tumor size >14mm and grade worse than well-differentiated, 5-year OS rates of 90.8 versus 82.3% (radio vs. nonradio, P <0.001).The deep learning network performed more stably and accurately in predicting patients survival than the random survival forest and Cox proportional hazard model on the internal test dataset (C-index=0.776 vs 0.641) and in the external validation(C-index=0.769 vs 0.650).Besides, the deep learning model identified several key factors that significantly influence patient survival, including tumor size, examined regional nodes, age at 45-49 years old and positive regional nodes (PRN). Conclusion: Patients with tumor size >14mm and age older than 54 and cohort with tumor size >14mm and grade worse than well-differentiated could benefit from the PMRT. The deep learning network performed more stably and accurately in predicting patients survival than Cox proportional hazard model on the internal test. Besides, tumor size, examined regional nodes, age at 45-49 years old and PRN are the most significant factors to the overall survival (OS).

Subjective well-being among PhD students in mainland China: the roles of psychological capital and academic engagement.

The mental well-being of PhD students is a major concern in higher education. However, very few studies have investigated the influencing factors of PhD students' subjective well-being (SWB) - an important indicator of mental well-being. Even no study on the influencing factors of PhD students' SWB has been undertaken in mainland China. Based on job demands-resources theory, the present study pioneers the investigation of the relationship between PhD students' psychological capital (PsyCap; comprising self-efficacy, hope, resilience, and optimism) and SWB (comprising positive affect, negative affect, and life satisfaction) in mainland China. It further examined the mediating role of academic engagement (comprising vigor, dedication, and absorption) in this relationship. PhD students (n = 376) from two comprehensive universities in Jiangsu province responded to an online survey. The results showed that (1) self-efficacy was positively associated with life satisfaction, hope was positively associated with positive affect, optimism was significantly associated with all three dimensions of SWB, but resilience was not significantly associated with any of the three SWB dimensions; and (2) dedication mediated the relationship between hope and life satisfaction and that between optimism and negative affect and life satisfaction, but vigor and absorption did not mediate any of the PsyCap-SWB relationships. Limitations and practical implications of this study are discussed.

Novel anti-inflammatory diketopiperazine alkaloids from the marine-derived fungus Penicillium brasilianum.

Diketopiperazine alkaloids have proven the most abundant heterocyclic alkaloids up to now, which usually process diverse scaffolds and rich biological activities. In our search for bioactive diketopiperazine alkaloids from marine-derived fungi, two novel diketopiperazine alkaloids, penipiperazine A (1) and its biogenetically related new metabolite (2), together with a known analogue neofipiperzine C (3), were obtained from the strain Penicillium brasilianum. Their planar structures and absolute configurations were elucidated by extensive spectroscopic analyses, 13C NMR calculation, Marfey's, ECD, and ORD methods. Compound 1 featured a unique 6/5/6/6/5 indole-pyrazino-pyrazino-pyrrolo system, and its plausible biogenetic pathway was also proposed. Additionally, compounds 1-3 have been tested for their inflammatory activities. 1 and 2 significantly inhibited the release of NO and the expression of related pro-inflammatory cytokines on LPS-stimulated RAW264.7 cells, suggesting they could be attracting candidate for further development as anti-inflammatory agent. KEY POINTS: • A novel diketopiperazine alkaloid featuring a unique 6/5/6/6/5 indole-pyrazino-pyrazino-pyrrolo system was isolated from the marine fungus Penicillium brasilianum. • The structure of 1 was elucidated by detailed analysis of 2D NMR data, 13C NMR calculation, Marfey's, ECD, and ORD methods. • Compounds 1 and 2 significantly inhibited the release of NO and the expression of related pro-inflammatory cytokines on LPS-stimulated RAW264.7 cells.

Ferroptosis and ferroptosis-inducing nanomedicine as a promising weapon in combination therapy of prostate cancer.

Incidence and mortality of prostate cancer (PCa) rank in the top five among male tumors. However, single treatment modalities are often restricted due to biochemical recurrence and drug resistance, necessitating the development of new approaches for the combination treatment of castration-resistant and neuroendocrine PCa. Ferroptosis is characterized by the accumulation of iron-overload-mediated lipid peroxidation and has shown promising outcomes in anticancer treatment, prompting us to present a review reporting the application of ferroptosis in the treatment of PCa. First, the process and mechanism of ferroptosis are briefly reviewed. Second, research advances combining ferroptosis-inducing agents and clinical treatment regimens, which exhibit a "two-pronged approach" effect, are further summarized. Finally, the recent progress on ferroptosis-inducing nanomaterials for combination anticancer therapy is presented. This review is expected to provide novel insights into ferroptosis-based combination treatment in drug-resistant PCa.

Synthesis and evaluation of WK-X-34 derivatives as P-glycoprotein (P-gp/ABCB1) inhibitors for reversing multidrug resistance.

The emergence of multidrug resistance (MDR) in malignant tumors is one of the leading threats encountered currently by many chemotherapeutic agents. A proposed strategy to overcome MDR is to disable the efflux function of P-glycoprotein (P-gp/ABCB1), a critical member of the ABC transporter family that significantly increases the efflux of various anticancer drugs from tumor cells. In this study, structural modification of a third-generation P-gp inhibitor WK-X-34 based on bioisosteric and fragment-growing strategies led to the discovery of the adamantane derivative PID-9, which exhibited the best MDR reversal activity (IC50 = 0.1338 µM, RF = 78.6) in this series, exceeding those of the reported P-gp inhibitors verapamil and WK-X-34. In addition, compared with WK-X-34, PID-9 showed decreased toxicity to cells. Furthermore, the mechanism studies revealed that the reversal activity of adamantane derivatives PID-5, PID-7, and PID-9 stemmed from the inhibition of P-gp efflux. These results indicated that compound PID-9 is the most effective P-gp inhibitor among them with low toxicity and high MDR reversal activity, which provided a fundamental structural reference for further discovery of novel, effective, and non-toxic P-gp inhibitors.

Genome-wide identification, evolution, and expression analysis of the NAC gene family in chestnut (Castanea mollissima).

The NAC gene family is one of the most important transcription factor families specific to plants, responsible for regulating many biological processes, including development, stress response, and signal transduction. However, it has not yet been characterized in chestnut, an important nut tree species. Here, we identified 115 CmNAC genes in the chestnut genome, which were divided into 16 subgroups based on the phylogenetic analysis. Numerous cis-acting elements related to auxin, gibberellin, and abscisic acid were identified in the promoter region of CmNACs, suggesting that they play an important role in the growth and development of chestnut. The results of the collinear analysis indicated that dispersed duplication and whole-genome-duplication were the main drivers of CmNAC gene expansion. RNA-seq data of developmental stages of chestnut nut, bud, and ovule revealed the expression patterns of CmNAC genes. Additionally, qRT-PCR experiments were used to verify the expression levels of some CmNAC genes. The comprehensive analysis of the above results revealed that some CmNAC members may be related to chestnut bud and nut development, as well as ovule fertility. The systematic analysis of this study will help to increase understanding of the potential functions of the CmNAC genes in chestnut growth and development.

Bioactive polyketides and meroterpenoids from the mangrove-derived fungus Talaromyces flavus TGGP35.

Six new polyketides, which includes three new lactones (talarotones A-C) (1-3), one new polyketide (talarotide A) (4), two new polyenes (talaroyenes A, B) (5, 6), together with one new meroterpenoid (talaropenoid A) (7) and 13 known compounds (8-20) were isolated from the mangrove-derived fungus Talaromyces flavus TGGP35. The structure and configuration of the compounds 1-7 were elucidated from the data obtained from HR-ESI-MS, IR, 1D/2D NMR spectroscopy, Mo2 (OAc)4-induced electronic circular dichroism (ECD), CD spectroscopy, and modified Mosher's method. Compounds 5 and 20 displayed antioxidant activity with IC50 values of 0.40 and 1.36 mM, respectively. Compounds 3, 6, 11, 16, and 17 displayed cytotoxic activity against human cancer cells Hela, A549, and had IC50 values ranging from 28.89 to 62.23 µM. Compounds 7, 10-12, and 14-18 exhibited moderate or potent anti-insect activity against newly hatched larvae of Helicoverpa armigera Hubner, with IC50 values in the range 50-200 µg/mL. Compound 18 showed antibacterial activity against Ralstonia solanacearum with the MIC value of 50 µg/mL.