The Impact of Weight Cycling on Health and Obesity.

Obesity is a systemic and chronic inflammation, which seriously endangers people's health. People tend to diet to control weight, and the short-term effect of dieting in losing weight is significant, but the prognosis is limited. With weight loss and recovery occurring frequently, people focus on weight cycling. The effect of weight cycling on a certain tissue of the body also has different conclusions. Therefore, this article systematically reviews the effects of body weight cycling on the body and finds that multiple weight cycling (1) increased fat deposition in central areas, lean mass decreased in weight loss period, and fat mass increased in weight recovery period, which harms body composition and skeletal muscle mass; (2) enhanced the inflammatory response of adipose tissue, macrophages infiltrated into adipose tissue, and increased the production of pro-inflammatory mediators in adipocytes; (3) blood glucose concentration mutation and hyperinsulinemia caused the increase or decrease in pancreatic ß-cell population, which makes ß-cell fatigue and leads to ß-cell failure; (4) resulted in additional burden on the cardiovascular system because of cardiovascular rick escalation. Physical activity combined with calorie restriction can effectively reduce metabolic disease and chronic inflammation, alleviating the adverse effects of weight cycling on the body.

Lenvatinib plus drug-eluting bead transarterial chemoembolization with/without hepatic arterial infusion chemotherapy for hepatocellular carcinoma larger than 7 cm with major portal vein tumor thrombosis: a multicenter retrospective cohort study.

BACKGROUND: The management of hepatocellular carcinoma (HCC) with high tumor burden and major portal vein tumor thrombosis (PVTT) remains a great challenge. We aimed to investigate the efficacy and safety of lenvatinib plus drug-eluting bead transarterial chemoembolization (DEB-TACE) and hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, fluorouracil and leucovorin (Len+DEB-TACE+HAIC) versus lenvatinib plus DEB-TACE (Len+DEB-TACE) for HCC > 7.0 cm accompanied with major PVTT. MATERIALS AND METHODS: This multicenter retrospective cohort study evaluated consecutive patients with HCC (> 7.0 cm) and major PVTT who received Len+DEB-TACE+HAIC (Len+DEB-TACE+HAIC group) or Len+DEB-TACE (Len+DEB-TACE group) between July 2019 and June 2021 from eight institutions in China. Objective response rate (ORR), time to progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were compared between the two groups by propensity score-matching (PSM). RESULTS: A total of 205 patients were included. After PSM, 85-paired patients remained in the study cohorts. Patients in the Len+DEB-TACE+HAIC group had higher ORR (61.2% vs. 34.1%, P < 0.001), longer TTP (median, 9.8 vs. 5.9 months, P < 0.001), and prolonged OS (median, 16.7 vs. 12.5 months, P < 0.001) than those in the Len+DEB-TACE group. The ORR and TTP of both intrahepatic tumor (ORR: 64.7% vs. 36.5%, P < 0.001; median TTP: 10.7 vs. 7.0 months, P < 0.001) and PVTT (ORR: 74.1% vs. 47.1%, P < 0.001; median TTP: 17.4 vs. 7.6 months, P < 0.001) were better in the Len+DEB-TACE+HAIC group than the Len+DEB-TACE group. The frequency of grade 3-4 TRAEs in the Len+DEB-TACE+HAIC group were comparable to those in the Len+DEB-TACE group (38.8% vs. 34.1%, P = 0.524). CONCLUSION: The addition of HAIC to Len+DEB-TACE significantly improved ORR, TTP, and OS over Len+DEB-TACE with an acceptable safety profile for large HCC with major PVTT.

Would the one-stage combined approach lead to better long-term neurological outcomes than the posterior approach alone in multilevel degenerative cervical myelopathy patients with T2-Weighted increased signal intensity? An 8-year follow-up results and propensity score matching analysis.

BACKGROUND: T2-weighted increased signal intensity (ISI) is commonly recognized as a sign of more severe spinal cord lesions, usually accompanied by worse neurological deficits and possibly worse postoperative neurological recovery. The combined approach could achieve better decompression and better neurological recovery for multilevel degenerative cervical myelopathy (MDCM). The choice of surgical approach for MDCM with intramedullary T2-weighted ISI remains disputed. This study aimed to compare the neurological outcomes of posterior and one-stage combined posteroanterior approaches for MDCM with T2-weighted ISI. METHODS: A total of 83 consecutive MDCM patients with confirmed ISI with at least three intervertebral segments operated between 2012 and 2014 were retrospectively enrolled. Preoperative demographic, radiological and clinical condition variables were collected, and neurological conditions were evaluated by the Japanese Orthopedic Assessment score (JOA) and Neck Disability Index (NDI). Propensity score matching analysis was conducted to produce pairs of patients with comparable preoperative conditions from the posterior-alone and combined groups. Both short-term and mid-term surgical outcomes were evaluated, including the JOA recovery rate (JOARR), NDI improvements, complications, and reoperations. RESULTS: A total of 83 patients were enrolled, of which 38 and 45 patients underwent posterior surgery alone and one-stage posteroanterior surgery, respectively. After propensity score matching, 38 pairs of comparable patients from the posterior and combined groups were matched. The matched groups presented similar preoperative clinical and radiological features and the mean follow-up duration were 111.6 ± 8.9 months. The preoperative JOA scores of the posterior and combined groups were 11.5 ± 2.2 and 11.1 ± 2.3, respectively (p = 0.613). The combined group presented with prolonged surgery duration(108.8 ± 28.0 and 186.1 ± 47.3 min, p = 0.028) and greater blood loss(276.3 ± 139.1 and 382.1 ± 283.1 ml, p<0.001). At short-term follow-up, the combined group presented a higher JOARR than the posterior group (posterior group: 50.7%±46.6%, combined group: 70.4%±20.3%, p = 0.024), while no significant difference in JOARR was observed between the groups at long-term follow-up (posterior group: 49.2%±48.5%, combined group: 59.6%±47.6%, p = 0.136). No significant difference was found in the overall complication and reoperation rates. CONCLUSIONS: For MDCM patients with ISI, both posterior and one-stage posteroanterior approaches could achieve considerable neurological alleviations in short-term and long-term follow-up. With greater surgical trauma, the combined group presented better short-term JOARR but did not show higher efficacy in long-term neurological function preservation in patients with comparable preoperative conditions.

Development and application of a risk nomogram for the prediction of risk of carbapenem-resistant Acinetobacter baumannii infections in neuro-intensive care unit: a mixed method study.

OBJECTIVE: This study aimed to develop and apply a nomogram with good accuracy to predict the risk of CRAB infections in neuro-critically ill patients. In addition, the difficulties and expectations of application such a tool in clinical practice was investigated. METHODS: A mixed methods sequential explanatory study design was utilized. We first conducted a retrospective study to identify the risk factors for the development of CRAB infections in neuro-critically ill patients; and further develop and validate a nomogram predictive model. Then, based on the developed predictive tool, medical staff in the neuro-ICU were received an in-depth interview to investigate their opinions and barriers in using the prediction tool during clinical practice. The model development and validation is carried out by R. The transcripts of the interviews were analyzed by Maxqda. RESULTS: In our cohort, the occurrence of CRAB infections was 8.63% (47/544). Multivariate regression analysis showed that the length of neuro-ICU stay, male, diabetes, low red blood cell (RBC) count, high levels of procalcitonin (PCT), and number of antibiotics ≥ 2 were independent risk factors for CRAB infections in neuro-ICU patients. Our nomogram model demonstrated a good calibration and discrimination in both training and validation sets, with AUC values of 0.816 and 0.875. Additionally, the model demonstrated good clinical utility. The significant barriers identified in the interview include "skepticism about the accuracy of the model", "delay in early prediction by the indicator of length of neuro-ICU stay", and "lack of a proper protocol for clinical application". CONCLUSIONS: We established and validated a nomogram incorporating six easily accessed indicators during clinical practice (the length of neuro-ICU stay, male, diabetes, RBC, PCT level, and the number of antibiotics used) to predict the risk of CRAB infections in neuro-ICU patients. Medical staff are generally interested in using the tool to predict the risk of CRAB, however delivering clinical prediction tools in routine clinical practice remains challenging.

Profound perturbations are found in the proteome and metabolome in children with obesity after weight loss intervention.

Background and aims: The mechanisms occur in children with obesity after lifestyle intervention remain poorly explained. Here, we investigated the serum proteomes and metabolomes of children with obesity who had undergone 30 days of weight loss intervention. Methods and results: Serum samples and clinical parameters were collected before and after lifestyle alteration interventions. Proteomic and metabolomic profiling was used to identify the differentially expressed proteins and differentially abundant metabolites in response to weight loss intervention. Lifestyle alteration interventions significantly decreased BMI, waist circumference, hip circumference and body fat, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL) and high non-HDL cholesterol, but not TG and high-density lipoprotein cholesterol (HDL), in children with obesity. By comparing the multiomics data, we identified 43 proteins and 165 metabolites that were significantly differentially expressed in children with obesity before and after lifestyle alteration interventions. Using integrated -omics analysis, we obtained 7 KEGG pathways that were organically integrated based on the correlations between differentially expressed proteins (DEPs) and metabolites (DMs). Further interaction analysis identified 7 proteins as candidate DEPs and 9 metabolites as candidate DMs. Interestingly, we found that some of these candidate DEPs and candidate DMs were significantly correlated with clinical parameters. Conclusion: Our results provide valuable proteome and metabolome data resources for better understanding weight loss-associated responses in children with obesity. In addition, we analyzed the number of significantly differentially expressed proteins and metabolites, shed new light on weight loss pathogenesis in children with obesity, and added potential therapeutic agents for obese children.

Full-endoscopic lumbar discectomy for lumbar disc herniation in young adults: 199 consecutive cases treated by a single surgeon with a mean 3.7-year follow-up.

OBJECTIVE: Lumbar disc herniation (LDH) is rare in young adults. The present study aimed to evaluate the clinical outcomes of full-endoscopic lumbar discectomy (FELD) for LDH in young adults and to determine the risk factors that predict unfavorable outcomes of FELD for LDH in young adults. METHODS: A retrospective two-center cohort study was performed between January 2015 and October 2021 at the authors' institutions. Clinical outcomes were assessed using the visual analog scale (VAS) for low-back pain and leg pain and the Oswestry Disability Index (ODI). The modified Macnab criteria were used to evaluate clinical efficacy at the last follow-up, and the global outcomes were classified into 4 groups, namely excellent, good, fair, and poor. The fair and poor groups were defined as unfavorable outcomes. RESULTS: One hundred ninety-nine patients were analyzed in this study (mean age 18.5 years, mean BMI 25.1 kg/m2, male/female sex ratio 2.8). The duration from the onset of symptoms to the operation was in general prolonged with age. The VAS and ODI scores significantly improved after surgery. A total of 17 of 195 single-segment cases had unfavorable outcomes based on the modified Macnab criteria. Lateral disc herniation (OR 3.72, 95% CI 1.14-12.12, p = 0.029) and high preoperative VAS score (OR 1.98, 95% CI 1.13-3.46, p = 0.017) were identified as risk factors for unfavorable outcomes after FELD. CONCLUSIONS: FELD for LDH in young adults is safe and effective. Preoperative VAS score and lateral disc herniation are risk factors of nonfavorable outcomes after surgery and may be a useful index for surgical procedure selection.

Pre-drying limitedly affected the yield, fuel properties, pyrolysis and combusion behavior of sewage sludge hydrochar.

While pre-drying of sewage sludge prior to hydrothermal carbonization is rarely practiced, various pre-drying methods have been performed in literature at lab-scale for convenient solid-to-liquid ratio adjustment. This has created a barrier for comparing hydrochar quality between different studies. Given pre-drying can destroy the floc structure of sewage sludge, we hypothesize that pre-drying may promote the hydrolysis step during hydrothermal carbonization process, resulting in improved hydrochar quality with low nitrogen content. In the current study, the influence of different pre-drying methods (freeze-dry, air-dry and vacuum-dry at 70 °C and 105 °C) on the subsequent hydrothermal carbonization of sewage sludge at 220 °C was assessed in terms of sewage sludge and hydrochar's chemical composition, fuel properties, pyrolysis and combustion behavior, as well as the characterization of the liquid phase. The results indicate that although pre-drying impacts sewage sludge's chemical composition, pyrolysis and combustion behavior, no significant differences exist in the yield, chemical composition, fuel properties, and pyrolysis and combustion behavior of the hydrochar. Therefore, the use of pre-drying would not affect the hydrothermal carbonization process of sewage sludge, and a comparison can be made on hydrochar quality between different studies with or without pre-drying.

Rapid recovery of high pure PbO from spent lead acid battery without desulfation and chemicals consumption method.

The direct recovery of high-purity PbO from spent lead paste without a pre-desulfation process has significant industrial promise. Herein, we propose a recyclable, ultra-fast, and high value-added closed-loop of high-purity PbO recovery process by intensive multidentate coordination of histidine with crude 2PbO·PbSO4 by a rotating liquid-film (RLF) reactor and CO2 carbonation-dissociation. Parameter optimizations and kinetic calculations show the leaching time is shortened from 40 min to 60 s with 99.14 % leaching rate and 99.99 % PbO purity by internal diffusion control, where the RLF reactor promotes mass transfer and reaction rates by instantly renewing the surface of crude 2PbO·PbSO4. Furthermore, all 5 batches reveal that the separation of SO42- ions from the regenerated mother liquid with Ba(OH)2 significantly improves the recycling rate of the mother liquid and high-purity PbO product. This new strategy reveals a bright prospect of a highly efficient, high value-added, and environmentally friendly recycling route for solid waste resources.

A chromosome-level haplotype-resolved genome assembly of oriental tobacco budworm (Helicoverpa assulta).

Oriental tobacco budworm (Helicoverpa assulta) and cotton bollworm (Helicoverpa armigera) are two closely related species within the genus Helicoverpa. They have similar appearances and consistent damage patterns, often leading to confusion. However, the cotton bollworm is a typical polyphagous insect, while the oriental tobacco budworm belongs to the oligophagous insects. In this study, we used Nanopore, PacBio, and Illumina platforms to sequence the genome of H. assulta and used Hifiasm to create a haplotype-resolved draft genome. The Hi-C technique helped anchor 33 primary contigs to 32 chromosomes, including two sex chromosomes, Z and W. The final primary haploid genome assembly was approximately 415.19 Mb in length. BUSCO analysis revealed a high degree of completeness, with 99.0% gene coverage in this genome assembly. The repeat sequences constituted 38.39% of the genome assembly, and we annotated 17093 protein-coding genes. The high-quality genome assembly of the oriental tobacco budworm serves as a valuable genetic resource that enhances our comprehension of how they select hosts in a complex odour environment. It will also aid in developing an effective control policy.

Evidence and Practical Applications of Site Occupancy Theory (SOT) of Eu3+ in Scheelite Compounds.

The determination of the site occupancy of activators in phosphors is essential for precise synthesis, understanding the relationship between their luminescence properties and crystal structure, and tailoring their properties by modifying the host composition. Herein, one simple method was proposed to help determine the sites at which the doping of rare earth ions or transition metal ions occupies in the host lattice through site occupancy theory (SOT) for ions doped into the matrix lattice. SOT was established based on the fact that doping ions preferentially occupy the sites with the lowest bonding energy deviations. In order to provide detailed experimental evidence to prove the feasibility of SOT, several scheelite-type compounds were successfully synthesized using a high-temperature solid-phase method. When Eu3+ ions occupy a similar surrounding environment site, the photoluminescence spectra of the activators Eu3+ are similar. Therefore, by comparing the intensity ratio of photoluminescence spectra and the mechanism of all transitions of KEu(WO4)2, KY(WO4)2:Eu3+, Na5Eu(WO4)4, and Na5Y(WO4)4:Eu3+, it was proved that SOT can successfully confirm the site occupation when doped ions enter the matrix lattice. SOT was further applied to the sites occupied by Eu3+ ion-doped LiAl(MoO4)2 and LiLu(MoO4)2.

Perioperative complications of en bloc resection and anterior column reconstruction for thoracic and lumbar spinal tumors.

PURPOSE: To evaluate the perioperative clinical outcomes of en bloc resection and anterior column reconstruction for thoracolumbar spinal tumors. METHODS: This study conducted a retrospective analysis of prospective data collection of 86 consecutive patients, including 40 males and 46 females, with an average age of 39 years (ranged from 10 to 71 years). There were 35 cases of a malignant primary tumor,42 cases of an aggressive benign tumor, and nine cases of metastases. The main lesions were located in 65 cases of thoracic spine, 17 cases of lumbar spine, and 4 cases of thoracolumbar spine. Tumors involved one level in 45 patients, two levels in 12 patients, three levels in 21 patients, four levels in five patients, five levels in two patients, and six levels in one patient. RESULTS: According to the Weinstein-Boriani-Biagini surgical staging system, all patients achieved en bloc resections, including 74 cases of total en bloc spondylectomy and 12 cases of sagittal resections. The mean surgical time was 559 min (210-1208 min), and the mean total blood loss was 1528 ml (260-5500 ml). A total of 122 complications were observed in 62(72.1%) patients, of which 18(20.9%) patients had 25 major complications and one patient (1.2%) died of complications. The combined approach (P = 0.002), total blood loss (P = 0.003), staged surgery (P = 0.004), previous surgical history (P = 0.045), the number of involved vertebrae (P = 0.021) and lumbar location (P = 0.012) were statistically significant risk factors for major complication. When all above risk factors were incorporated in multivariate analysis, only the combined approach (P = 0.052) still remained significant. CONCLUSIONS: En bloc resection and anterior column reconstruction is accompanied by a high incidence of complications, especially when a combined approach is necessary.

Exploring the casual association between gut microbiome, circulating inflammatory cytokines and chronic pancreatitis: A Mendelian randomization analysis.

It has been established that gut dysbiosis contributed to the pathogenesis of digestive disorders. We aimed to explore the causal relationships between intestinal microbiota, circulating inflammatory cytokines and chronic pancreatitis (CP). Summary statistics of genome-wide association studies (GWAS) of intestinal microbiome was retrieved from the MiBioGen study and the GWAS data of 91 circulating inflammatory cytokines and CP were obtained from the GWAS catalog. The 2-sample bidirectional Mendelian randomization (MR) analysis was performed between gut microbiota, circulating inflammatory cytokines and CP, in which the inverse variance weighted (IVW) method was regarded as the primary analysis approach. To prove the reliability of the causal estimations, multiple sensitivity analyses were utilized. IVW results revealed that genetically predicted 2 genera, including Sellimonas and Eubacteriumventriosumgroup, and plasm C-C motif chemokine 23 (CCL23) level were positively associated with CP risk, while genus Escherichia Shigella, Eubacteriumruminantiumgroup and Prevotella9, and plasma Caspase 8, Adenosine Deaminase (ADA), and SIR2-like protein 2 (SIRT2) level, demonstrated an ameliorative effect on CP. Leave-one-out analysis confirmed the robustness of the aforementioned causal effects and no significant horizontal pleiotropy or heterogeneity of the instrumental variables was detected. However, no association was found from the identified genera to the CP-related circulating inflammatory cytokines. Besides, the reverse MR analysis demonstrated no causal relationship from CP to the identified genera and circulating inflammatory cytokines. Taken together, our comprehensive analyses offer evidence in favor of the estimated causal connections from the 5 genus-level microbial taxa and 4 circulating inflammatory cytokines to CP risk, which may help to reveal the underlying pathogenesis of CP.

Unraveling ETC complex I function in ferroptosis reveals a potential ferroptosis-inducing therapeutic strategy for LKB1-deficient cancers.

The role of the mitochondrial electron transport chain (ETC) in regulating ferroptosis is not fully elucidated. Here, we reveal that pharmacological inhibition of the ETC complex I reduces ubiquinol levels while decreasing ATP levels and activating AMP-activated protein kinase (AMPK), the two effects known for their roles in promoting and suppressing ferroptosis, respectively. Consequently, the impact of complex I inhibitors on ferroptosis induced by glutathione peroxidase 4 (GPX4) inhibition is limited. The pharmacological inhibition of complex I in LKB1-AMPK-inactivated cells, or genetic ablation of complex I (which does not trigger apparent AMPK activation), abrogates the AMPK-mediated ferroptosis-suppressive effect and sensitizes cancer cells to GPX4-inactivation-induced ferroptosis. Furthermore, complex I inhibition synergizes with radiotherapy (RT) to selectively suppress the growth of LKB1-deficient tumors by inducing ferroptosis in mouse models. Our data demonstrate a multifaceted role of complex I in regulating ferroptosis and propose a ferroptosis-inducing therapeutic strategy for LKB1-deficient cancers.

PQSDC: a parallel lossless compressor for quality scores data via sequences partition and run-length prediction mapping.

MOTIVATION: The quality scores data (QSD) account for 70% in compressed FastQ files obtained from the short and long reads sequencing technologies. Designing effective compressors for QSD that counterbalance compression ratio, time cost, and memory consumption is essential in scenarios such as large-scale genomics data sharing and long-term data backup. This study presents a novel parallel lossless QSD-dedicated compression algorithm named PQSDC, which fulfills the above requirements well. PQSDC is based on two core components: a parallel sequences-partition model designed to reduce peak memory consumption and time cost during compression and decompression processes, as well as a parallel four-level run-length prediction mapping model to enhance compression ratio. Besides, the PQSDC algorithm is also designed to be highly concurrent using multicore CPU clusters. RESULTS: We evaluate PQSDC and four state-of-the-art compression algorithms on 27 real-world datasets, including 61.857 billion QSD characters and 632.908 million QSD sequences. (1) For short reads, compared to baselines, the maximum improvement of PQSDC reaches 7.06% in average compression ratio, and 8.01% in weighted average compression ratio. During compression and decompression, the maximum total time savings of PQSDC are 79.96% and 84.56%, respectively; the maximum average memory savings are 68.34% and 77.63%, respectively. (2) For long reads, the maximum improvement of PQSDC reaches 12.51% and 13.42% in average and weighted average compression ratio, respectively. The maximum total time savings during compression and decompression are 53.51% and 72.53%, respectively; the maximum average memory savings are 19.44% and 17.42%, respectively. (3) Furthermore, PQSDC ranks second in compression robustness among the tested algorithms, indicating that it is less affected by the probability distribution of the QSD collections. Overall, our work provides a promising solution for QSD parallel compression, which balances storage cost, time consumption, and memory occupation primely. AVAILABILITY AND IMPLEMENTATION: The proposed PQSDC compressor can be downloaded from https://github.com/fahaihi/PQSDC.

An Innovative Mitochondrial-targeted Gene Therapy for Cancer Treatment.

Targeting cancer cell mitochondria holds great therapeutic promise, yet current strategies to specifically and effectively destroy cancer mitochondria in vivo are limited. Here, we introduce mLumiOpto, an innovative mitochondrial-targeted luminoptogenetics gene therapy designed to directly disrupt the inner mitochondrial membrane (IMM) potential and induce cancer cell death. We synthesize a blue light-gated channelrhodopsin (CoChR) in the IMM and co-express a blue bioluminescence-emitting Nanoluciferase (NLuc) in the cytosol of the same cells. The mLumiOpto genes are selectively delivered to cancer cells in vivo by using adeno-associated virus (AAV) carrying a cancer-specific promoter or cancer-targeted monoclonal antibody-tagged exosome-associated AAV. Induction with NLuc luciferin elicits robust endogenous bioluminescence, which activates mitochondrial CoChR, triggering cancer cell IMM permeability disruption, mitochondrial damage, and subsequent cell death. Importantly, mLumiOpto demonstrates remarkable efficacy in reducing tumor burden and killing tumor cells in glioblastoma or triple-negative breast cancer xenografted mouse models. These findings establish mLumiOpto as a novel and promising therapeutic strategy by targeting cancer cell mitochondria in vivo.

DePARylation is critical for S phase progression and cell survival.

Poly(ADP-ribose)ylation or PARylation by PAR polymerase 1 (PARP1) and dePARylation by poly(ADP-ribose) glycohydrolase (PARG) are equally important for the dynamic regulation of DNA damage response. PARG, the most active dePARylation enzyme, is recruited to sites of DNA damage via pADPr-dependent and PCNA-dependent mechanisms. Targeting dePARylation is considered an alternative strategy to overcome PARP inhibitor resistance. However, precisely how dePARylation functions in normal unperturbed cells remains elusive. To address this challenge, we conducted multiple CRISPR screens and revealed that dePARylation of S phase pADPr by PARG is essential for cell viability. Loss of dePARylation activity initially induced S-phase-specific pADPr signaling, which resulted from unligated Okazaki fragments and eventually led to uncontrolled pADPr accumulation and PARP1/2-dependent cytotoxicity. Moreover, we demonstrated that proteins involved in Okazaki fragment ligation and/or base excision repair regulate pADPr signaling and cell death induced by PARG inhibition. In addition, we determined that PARG expression is critical for cellular sensitivity to PARG inhibition. Additionally, we revealed that PARG is essential for cell survival by suppressing pADPr. Collectively, our data not only identify an essential role for PARG in normal proliferating cells but also provide a potential biomarker for the further development of PARG inhibitors in cancer therapy.

Transcriptome and single-cell analysis reveal disulfidptosis-related modification patterns of tumor microenvironment and prognosis in osteosarcoma.

Osteosarcoma (OS) is the most common malignant bone tumor with high pathological heterogeneity. Our study aimed to investigate disulfidptosis-related modification patterns in OS and their relationship with survival outcomes in patients with OS. We analyzed the single-cell-level expression profiles of disulfidptosis-related genes (DSRGs) in both OS microenvironment and OS subclusters, and HMGB1 was found to be crucial for intercellular regulation of OS disulfidptosis. Next, we explored the molecular clusters of OS based on DSRGs and related immune cell infiltration using transcriptome data. Subsequently, the hub genes of disulfidptosis in OS were screened by applying multiple machine models. In vitro and patient experiments validated our results. Three main disulfidptosis-related molecular clusters were defined in OS, and immune infiltration analysis suggested high immune heterogeneity between distinct clusters. The in vitro experiment confirmed decreased cell viability of OS after ACTB silencing and higher expression of ACTB in patients with lower immune scores. Our study systematically revealed the underlying relationship between disulfidptosis and OS at the single-cell level, identified disulfidptosis-related subtypes, and revealed the potential role of ACTB expression in OS disulfidptosis.

Application of TCM Nursing in Post-anesthesia Recovery Room Under Integrated Management Mode.

Objective: To explore the effect of traditional Chinese medicine (TCM) nursing under the integrated management mode during anesthesia recovery. Methods: The researchers' hospital admitted 114 patients who underwent general anesthesia between August 2022 and April 2023. Based on the admission order, these patients were divided into a control group (N=57) and an observation group (N=57). The control group received routine nursing intervention, while the observation group received comprehensive TCM nursing management, which included therapies such as cupping, acupressure, massage, herbal decoction, and mirabilite application. The study evaluated the psychological status, recovery indexes after anesthesia, comfort level, incidence of complications, and patient satisfaction with nursing care. Results: Compared to the control group, the observation group showed significant improvement in their psychological well-being (P < .05) and better recovery outcomes after anesthesia (P < .05). Additionally, the observation group reported higher levels of comfort (P < .05), a lower incidence of complications (8.77% vs 29.82%, P < .05), and greater satisfaction with nursing care (98.25% vs 84.21%, P < .05) compared to the control group. Conclusion: Integrated management of traditional Chinese medicine effectively reduces postoperative adverse events, improves treatment outcomes, and facilitates patient recovery. Its benefits are evident, and its feasibility is well-established.

Proteomic analysis of ferroptosis pathways reveals a role of CEPT1 in suppressing ferroptosis.

Ferroptosis has been recognized as a unique cell death modality driven by excessive lipid peroxidation and unbalanced cellular metabolism. In this study, we established a protein interaction landscape for ferroptosis pathways through proteomic analyses, and identified choline/ethanolamine phosphotransferase 1 (CEPT1) as a lysophosphatidylcholine acyltransferase 3 (LPCAT3)-interacting protein that regulates LPCAT3 protein stability. In contrast to its known role in promoting phospholipid synthesis, we showed that CEPT1 suppresses ferroptosis potentially by interacting with phospholipases and breaking down certain pro-ferroptotic polyunsaturated fatty acid (PUFA)-containing phospholipids. Together, our study reveals a previously unrecognized role of CEPT1 in suppressing ferroptosis.

BRCA1-mediated dual regulation of ferroptosis exposes a vulnerability to GPX4 and PARP co-inhibition in BRCA1-deficient cancers.

Resistance to poly (ADP-ribose) polymerase inhibitors (PARPi) limits the therapeutic efficacy of PARP inhibition in treating breast cancer susceptibility gene 1 (BRCA1)-deficient cancers. Here we reveal that BRCA1 has a dual role in regulating ferroptosis. BRCA1 promotes the transcription of voltage-dependent anion channel 3 (VDAC3) and glutathione peroxidase 4 (GPX4); consequently, BRCA1 deficiency promotes cellular resistance to erastin-induced ferroptosis but sensitizes cancer cells to ferroptosis induced by GPX4 inhibitors (GPX4i). In addition, nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and defective GPX4 induction unleash potent ferroptosis in BRCA1-deficient cancer cells upon PARPi and GPX4i co-treatment. Finally, we show that xenograft tumors derived from BRCA1-mutant breast cancer patients with PARPi resistance exhibit decreased GPX4 expression and high sensitivity to PARP and GPX4 co-inhibition. Our results show that BRCA1 deficiency induces a ferroptosis vulnerability to PARP and GPX4 co-inhibition and inform a therapeutic strategy for overcoming PARPi resistance in BRCA1-deficient cancers.