Structural Basis for Polθ-Helicase DNA Binding and Microhomology-Mediated End-Joining.

DNA double-strand breaks (DSBs) present a critical threat to genomic integrity, often precipitating genomic instability and oncogenesis. Repair of DSBs predominantly occurs through homologous recombination (HR) and non-homologous end joining (NHEJ). In HR-deficient cells, DNA polymerase theta (Polθ) becomes critical for DSB repair via microhomology-mediated end joining (MMEJ), also termed theta-mediated end joining (TMEJ). Thus, Polθ is synthetically lethal with BRCA1/2 and other HR factors, underscoring its potential as a therapeutic target in HR-deficient cancers. However, the molecular mechanisms governing Polθ-mediated MMEJ remain poorly understood. Here we present a series of cryo-electron microscopy structures of the Polθ helicase domain (Polθ-hel) in complex with DNA containing 3'-overhang. The structures reveal the sequential conformations adopted by Polθ-hel during the critical phases of DNA binding, microhomology searching, and microhomology annealing. The stepwise conformational changes within the Polθ-hel subdomains and its functional dimeric state are pivotal for aligning the 3'-overhangs, facilitating the microhomology search and subsequent annealing necessary for DSB repair via MMEJ. Our findings illustrate the essential molecular switches within Polθ-hel that orchestrate the MMEJ process in DSB repair, laying the groundwork for the development of targeted therapies against the Polθ-hel.

Biodegradation of bisphenol A by a Pichia pastoris whole-cell biocatalyst with overexpression of laccase from Bacillus pumilus and investigation of its potential degradation pathways.

Bisphenol A (BPA), an endocrine disrupter with estrogen activity, can infiltrate animal and human bodies through the food chain. Enzymatic degradation of BPA holds promise as an environmentally friendly approach while it is limited due to lower stability and recycling challenges. In this study, laccase from Bacillus pumilus TCCC 11568 was expressed in Pichia pastoris (fLAC). The optimal catalytic conditions for fLAC were at pH 6.0 and 80 °C, with a half-life T1/2 of 120 min at 70 °C. fLAC achieved a 46 % degradation rate of BPA, and possible degradation pathways were proposed based on identified products and reported intermediates of BPA degradation. To improve its stability and degradation capacity, a whole-cell biocatalyst (WCB) was developed by displaying LAC (dLAC) on the surface of P. pastoris GS115. The functionally displayed LAC demonstrated enhanced thermostability and pH stability along with an improved BPA degradation ability, achieving a 91 % degradation rate. Additionally, dLAC maintained a degradation rate of over 50 % after the fourth successive cycles. This work provides a powerful catalyst for degrading BPA, which might decontaminate endocrine disruptor-contaminated water through nine possible pathways.

When quantum dots meet blue phase liquid crystal elastomers: visualized full-color and mechanically-switchable circularly polarized luminescence.

Polymer-based circularly polarized luminescence (CPL) materials with the advantage of diversified structure, easy fabrication, high thermal stability, and tunable properties have garnered considerable attention. However, adequate and precise tuning over CPL in polymer-based materials remains challenging due to the difficulty in regulating chiral structures. Herein, visualized full-color CPL is achieved by doping red, green, and blue quantum dots (QDs) into reconfigurable blue phase liquid crystal elastomers (BPLCEs). In contrast to the CPL signal observed in cholesteric liquid crystal elastomers (CLCEs), the chiral 3D cubic superstructure of BPLCEs induces an opposite CPL signal. Notably, this effect is entirely independent of photonic bandgaps (PBGs) and results in a high glum value, even without matching between PBGs and the emission bands of QDs. Meanwhile, the lattice structure of the BPLCEs can be reversibly switched via mechanical stretching force, inducing on-off switching of the CPL signals, and these variations can be further fixed using dynamic disulfide bonds in the BPLCEs. Moreover, the smart polymer-based CPL systems using the BPLCEs for anti-counterfeiting and information encryption have been demonstrated, suggesting the great potential of the BPLCEs-based CPL active materials.

Endogenous Type I-C CRISPR-Cas system of Streptococcus equi subsp. zooepidemicus promotes biofilm formation and pathogenicity.

Streptococcus equi subsp. zooepidemicus (SEZ) is a significant zoonotic pathogen that causes septicemia, meningitis, and mastitis in domestic animals. Recent reports have highlighted high-mortality outbreaks among swine in the United States. Traditionally recognized for its adaptive immune functions, the CRISPR-Cas system has also been implicated in gene regulation, bacterial pathophysiology, virulence, and evolution. The Type I-C CRISPR-Cas system, which is prevalent in SEZ isolates, appears to play a pivotal role in regulating the pathogenicity of SEZ. By constructing a Cas3 mutant strain (ΔCas3) and a CRISPR-deficient strain (ΔCRISPR), we demonstrated that this system significantly promotes biofilm formation and cell adhesion. However, the deficiency in the CRISPR-Cas system did not affect bacterial morphology or capsule production. In vitro studies showed that the CRISPR-Cas system enhances pro-inflammatory responses in RAW264.7 cells. The ΔCas3 and ΔCRISPR mutant strains exhibited reduced mortality rates in mice, accompanied by a decreased bacterial load in specific organs. RNA-seq analysis revealed distinct expression patterns in both mutant strains, with ΔCas3 displaying a broader range of differentially expressed genes, which accounted for over 70% of the differential genes observed in ΔCRISPR. These genes were predominantly linked to lipid metabolism, the ABC transport system, signal transduction, and quorum sensing. These findings enhance our understanding of the complex role of the CRISPR-Cas system in SEZ pathogenesis and provide valuable insights for developing innovative therapeutic strategies to combat infections.

Direct Observation of Anionic Yields from the Liquid-Vapor Interface by Electron Irradiation.

Dissociative electron attachment (DEA) is widely believed to play a high-profile role in ionizing radiation damages of bioorganic molecules, and its fundamentals are mainly learned from the gas-phase studies. However, the DEA process in aqueous solution is still in debate. Here we provide experimental evidence about the DEA processes of liquid methanol by using electron-impact-time-delayed mass spectrometry. In contrast to the gas- and solid-phase DEAs, methoxide ion CH3O- is the predominant product from the liquid interface. Furthermore, this anion can be produced with both the primary low-energy electrons and the inelastically scattered and secondary low-energy electrons. On the contrary, the primary low-energy electrons in the liquid bulk are more likely to be solvated, rather than directly participating in the DEA process. Our study provides new insights into radiation chemistry, particularly of bioorganic relevance.

Special diffusion pathway of pericoronitis of the third molar: A case report and literature review.

INTRODUCTION: Pericoronitis of wisdom teeth along the jaw diffusion may be a rare diffusion pathway, which can cause osteomyelitis and maxillofacial space infection serious complications. PRESENTATION OF CASE: A 62-years-old male patient presented with swelling and discomfort of the right cheek for more than 1 year. The patient was previously healthy and denied various systemic medical histories. The patient's face was asymmetric, the right cheek was swollen, and the depressed edema was seen on the surface of the masseter area of the right parotid gland. Based on the preoperative cone-beam computed tomography (CBCT) imaging results, the initial diagnosis was: centralized osteomyelitis of the jaws. The surgical plan was minimally invasive extraction 48 and localized debridement of the lesion area. After three months of follow-up, the patient's symptoms were significantly improved without recurrence. DISCUSSION: Pericoronitis of wisdom teeth along the jaw diffusion is a rare diffusion pathway, which can lead to secondary jaw osteomyelitis, the treatment of which consists of lesion debridement, dead bone curettage and antibiotic therapy. CONCLUSION: Through literature review and summary of the diagnosis and treatment process of this case, such cases should be diagnosed as early as possible and conservative treatment should be actively used to avoid the occurrence of complications. In addition, the special diffusion pathway of this case may provide a new theoretical basis for the source of infection of central jaw osteomyelitis.

Rhodopseudomonas palustris shapes bacterial community, reduces Cd bioavailability in Cd contaminated flooding paddy soil, and improves rice performance.

Photosynthetic bacteria (PSB) are suitable to live and remediate cadmium (Cd) in the slightly oxygenated or anaerobic flooding paddy field. However, there is currently limited study on the inhibition of Cd accumulation in rice by PSB, and the relevant mechanisms has yet to be elucidated. In the current study, we firstly used Rhodopseudomonas palustris SC06 (a typical PSB) as research target and combined physiology, biochemistry, microbiome and metabolome to evaluate the mechanisms of remeding Cd pollution in paddy field and inhibiting Cd accumulation in rice. Microbiome analysis results revealed that intensive inoculation with R. palustris SC06 successfully survived and multiplied in flooding paddy soil, and significantly increased the relatively abundance of anaerobic bacteria including Desulfobacterota, Anaerolineaceae, Geobacteraceae, and Gemmatimonadaceae by 46.40 %, 45.00 %, 50.12 %, and 21.30 %, respectively. Simultaneously, the structure of microbial community was regulated to maintain relative stability in the rhizosphere soil of rice under Cd stress. In turn, these bacteria communities reduced bioavailable Cd and enhanced residual Cd in soil, and induced the upregulation of sugar and organic acids in the rice roots, which further inhibited Cd uptake in rice seedlings, and dramatically improved the photosynthetic efficiency in the leaves and the activities of antioxidative enzymes in the roots. Finally, Cd content of the roots, stems, leaves, and grains significantly decreased by 38.14 %, 69.10 %, 83.40 %, and 37.24 % comparing with the control, respectively. This study provides a new strategy for the remediation of Cd-contaminated flooding paddy fields and the safe production of rice.

Association between dietary inflammatory potential and frailty is mediated by inflammation among patients with colorectal cancer: A cross-sectional study.

Patients with colorectal cancer (CRC) are at high risk of frailty, leading to reduced quality of life and survival. Diet is associated with frailty in the elderly through regulating inflammation. Thus, we hypothesized that dietary inflammatory potential (as assessed by dietary inflammatory index [DII]) might be associated with frailty in patients with CRC through regulating inflammatory biomarkers. A total of 231 patients with CRC were included in this cross-sectional study. Dietary intake was evaluated by 3-day, 24-hour dietary recalls, and frailty status was assessed in accordance with the Fried frailty criteria. Plasma inflammatory cytokines were determined in 126 blood samples. A total of 67 patients (29.0%) were frail, with significantly higher DII scores than nonfrail patients, accompanied with significantly increased interleukin-6 (IL-6) and decreased interleukin-10 (IL-10) concentrations. Each 1-point increase of DII was related to a 25.0% increased risk of frailty. IL-6 was positively correlated with frailty and DII, whereas IL-10 was negatively correlated. After adjusting for age, sex, body mass index, education level, smoking status, and energy, mediation analysis revealed that the association between DII and frailty was significantly mediated by IL-6 (average causal mediation effect [ACME], 0.052; 95% confidence interval, 0.020-0.087; P = .002) and IL-10 (ACME, 0.025; 95% confidence interval, 0.004-0.063; P = .016). The ρ values for the sensitivity measure at which estimated ACMEs were zero were 0.3 and -0.2 for IL-6 and IL-10, respectively. Therefore, a pro-inflammatory diet was associated with frailty in patients with CRC possibly in part by affecting circulating IL-6 and IL-10 concentrations.

Nanowire Array Breath Acetone Sensor for Diabetes Monitoring.

Diabetic ketoacidosis (DKA) is a life-threatening acute complication of diabetes characterized by the accumulation of ketone bodies in the blood. Breath acetone, a ketone, directly correlates with blood ketones. Therefore, monitoring breath acetone can significantly enhance the safety and efficacy of diabetes care. In this work, the design and fabrication of an InP/Pt/chitosan nanowire array-based chemiresistive acetone sensor is reported. By incorporation of chitosan as a surface-functional layer and a Pt Schottky contact for efficient charge transfer processes and photovoltaic effect, self-powered, highly selective acetone sensing is achieved. The sensor has exhibited an ultra-wide acetone detection range from sub-ppb to >100 000 ppm level at room temperature, covering those in the exhaled breath from healthy individuals (300-800 ppb) to people at high risk of DKA (>75 ppm). The nanowire sensor has also been successfully integrated into a handheld breath testing prototype, the Ketowhistle, which can successfully detect different ranges of acetone concentrations in simulated breath samples. The Ketowhistle demonstrates the immediate potential for non-invasive ketone monitoring for people living with diabetes, in particular for DKA prevention.

Unveiling the destabilization of sp3 and sp2 bonds in transition metal-modified borohydrides to improve reversible dehydrogenation and rehydrogenation.

Borohydrides offer promise as potential carriers for hydrogen storage due to their high hydrogen concentration. However, the strong chemical bonding within borohydrides poses challenges for efficient hydrogen release during usage and restricts the re-hydrogenation process when attempting to regenerate the material. These high thermodynamic and kinetic barriers present obstacles in achieving reversible de-hydrogenation and re-hydrogenation of borohydrides, impeding their practical application in hydrogen storage systems. Employing density functional theory calculations, we conduct a comprehensive investigation into the influence of transition metals on both the BH4 cluster, a fundamental building block of borohydrides, and pure boron, which is formed as the end product following hydrogen release. Our research reveals correlations among the d-band center, work function, and surface energy of 3d and 4d transition metals. These correlations are directly linked to the weakening of bonding within the BH4 cluster when adsorbed on catalyst surfaces. On the other hand, we also explore how various intrinsic properties of transition metals influence the formation of boron vacancies and the hydrogen bonding process. By establishing a comprehensive correlation between the weakening of sp3 hybridization in the BH4 cluster and the sp2 hybridization in boron, we facilitate the identification and screening of optimal candidates capable of achieving reversible de-hydrogenation and re-hydrogenation in borohydrides.

Effect of Double-Ovsynch and Presynch-Ovsynch on postpartum ovarian cysts and inactive ovary in high-yielding dairy cows.

Introduction: Optimizing the management of dairy cattle reproduction can reduce postpartum ovarian disease in high-yielding dairy cows and thus enhance ranch economic benefit. The hypothesis of this study was that the Double-Ovsynch (DO) protocol in high-producing dairy cows would result in a lower incidence of follicular cysts but a higher incidence of luteal cysts compared to those undergoing the Presynch-Ovsynch (PS) protocol. Methods: In this experiment, 384 cows (204 primiparous and 180 multiparous) were allocated to the DO group, which followed the protocol: GnRH-7d-PGF2α-3d-GnRH-7d-Ovsynch-56 h (GnRH-7d-PGF2α-56 h-GnRH-16hTAI), starting on 39 ± 3 days in milk (DIM). Additionally, 359 cows (176 primiparous and 183 multiparous) were assigned to the PS group, which followed the protocol: PGF2α-14d-PGF2α-12d-Ovsynch-56 h, starting on 31 ± 3 DIM. In DO, B-mode ultrasound examinations were conducted 1 day after the GnRH-7d-PGF2α-3d-GnRH protocol to diagnose the presence of ovarian diseases followed by reexamination after 7 days of suspected cases. In PS, B-mode ultrasound examinations were conducted 1 day after the PGF2α-14d-PGF2α protocol to diagnose the presence of ovarian diseases followed by reexamination after 7 days. For all cows confirmed to having ovarian diseases, a second B-mode ultrasound examination was conducted at the time of the second GnRH and timed artificial insemination (TAI). If the ovary showed a normal developing follicle in combination with normal ovulation, the ovarian disease was considered to be cured. Results: The current study revealed no significant difference in the overall incidence and cure rate of postpartum ovarian diseases between DO and PS (incidence rate: 3.9% vs. 6.7%, cure rate: 50% vs. 41.7%, DO vs. PS). Also, there was no significant difference in the incidence and cure rate of luteal cysts between DO and PS (incidence rate: 2.9% vs. 2.2%, cure rate: 50.0% vs. 50.0%). The incidence of follicular cysts was significantly lower in the DO group than in the PS group (0.8% vs. 2.8%, DO vs. PS, p = 0.037), but there was no significant difference in the cure rates (66.7% vs. 50%). The occurrence of inactive ovary was lower in DO compared to PS (0.2% vs. 1.7%, p = 0.047). There was no significant difference in the pregnancy rate between the DO and PS groups (48.2% vs. 41.8%), although the DO group had a higher rate. What is different from our assumption is that PS did not effectively reduce the incidence of postpartum luteal cysts.

Airborne magnetite nanoparticles induced early vascular pathologies by disrupting lipid metabolism under high-fat dietary patterns.

Magnetite nanoparticles (MNPs) have been extensively detected in the atmospheric environment and implicated as a prominent threat to atherosclerosis, a chronic vascular inflammatory disease. Due to globalization and economic development, the dramatic shift in diet from traditional to high-fat dietary patterns aggravated atherosclerosis progression induced by environmental factors. However, limited knowledge is available regarding vascular risks and underlying mechanisms of airborne MNPs in high-risk populations with high-fat dietary habits. Herein, we demonstrated that MNPs exerted a proatherogenic effect under high-fat dietary patterns, leading to aortic wall thickening, elastic fiber disorganization, macrophage infiltration, and local inflammation. Based on the correlation analysis between MNPs and PM group, we identified that MNPs might be a key PM component in atherogenic toxicity. MNPs exposure disturbed the dynamic process of lipid metabolism, manifested as aortic lipid accumulation, dyslipidemia, and hepatic lipid metabolism disorder, which was modulated by the JAK-STAT pathway. Overall, these findings provide new insight into understanding the cardiovascular risks and mechanisms of MNPs among high-risk populations.

Peripheral inflammation is a potential etiological factor in Alzheimer's disease.

Peripheral inflammation could constitute a risk factor for AD. This review summarizes the research related to peripheral inflammation that appears to have a relationship with Alzheimer's disease. We find there are significant associations between AD and peripheral infection induced by various pathogens, including herpes simplex virus type 1, cytomegalovirus, Epstein-Barr virus, human immunodeficiency virus, severe acute respiratory syndrome coronavirus 2, Porphyromonas gingivalis, Helicobacter pylori, and Toxoplasma gondii. Chronic inflammatory diseases are also reported to contribute to the pathophysiology of AD. The mechanisms by which peripheral inflammation affects the pathophysiology of AD are complex. Pathogen-derived neurotoxic molecule composition, disrupted BBB, and dysfunctional neurogenesis may all play a role in peripheral inflammation, promoting the development of AD. Anti-pathogenic medications and anti-inflammatory treatments are reported to decrease the risk of AD. Studies that could improve understanding the associations between AD and peripheral inflammation are needed. If our assumption is correct, early intervention against inflammation may be a potential method of preventing and treating AD.

Silica nanoparticles induce ferroptosis of HUVECs by triggering NCOA4-mediated ferritinophagy.

Silica nanoparticles (SiNPs) have been widely used in electronics, chemistry, and biomedicine. Human exposure to SiNPs and possible health effects have attracted much attention. The potential cardiovascular toxicity of SiNPs and their related mechanisms are still unclear. Therefore, in this study, we investigated the toxic effects of SiNPs on human umbilical vein endothelial cells (HUVECs). We found that SiNPs could induce HUVECs ferroptosis. The results showed that the level of intracellular divalent iron and lipid peroxidation increased, and mitochondrial cristae decreased. In addition, the pretreatment of the iron chelator deferoxamine mesylate (DFO) could alleviate the ferroptosis of cells. Interestingly, pretreatment of 3-methyladenine (3-MA), an autophagy/PI3K inhibitor could partially inhibit autophagy and reduce ferroptosis, which indicated that autophagy played an important role in cell ferroptosis. Additionally, after knocking down nuclear receptor coactivator 4 (NCOA4), Ferritin Heavy Chain 1 (FTH1) expression was up-regulated, and the levels of divalent iron and lipid peroxidation decreased, which suggested that NCOA4 mediated the ferroptosis of HUVECs induced by SiNPs. In conclusion, this study shows that SiNPs can induce cardiovascular toxicity in which there is ferroptosis. NCOA4-mediated ferritinophagy and resultant ferroptosis by SiNPs may play an important role. This study provides a new theoretical strategy for the treatment and prevention of cardiovascular diseases in the future.

Single-cell transcriptomic atlas of goat ovarian aging.

BACKGROUND: The ovaries are one of the first organs that undergo degenerative changes earlier in the aging process, and ovarian aging is shown by a decrease in the number and quality of oocytes. However, little is known about the molecular mechanisms of female age-related fertility decline in different types of ovarian cells during aging, especially in goats. Therefore, the aim of this study was to reveal the mechanisms driving ovarian aging in goats at single-cell resolution. RESULTS: For the first time, we surveyed the single-cell transcriptomic landscape of over 27,000 ovarian cells from newborn, young and aging goats, and identified nine ovarian cell types with distinct gene-expression signatures. Functional enrichment analysis showed that ovarian cell types were involved in their own unique biological processes, such as Wnt beta-catenin signalling was enriched in germ cells, whereas ovarian steroidogenesis was enriched in granulosa cells (GCs). Further analysis showed that ovarian aging was linked to GCs-specific changes in the antioxidant system, oxidative phosphorylation, and apoptosis. Subsequently, we identified a series of dynamic genes, such as AMH, CRABP2, THBS1 and TIMP1, which determined the fate of GCs. Additionally, FOXO1, SOX4, and HIF1A were identified as significant regulons that instructed the differentiation of GCs in a distinct manner during ovarian aging. CONCLUSIONS: This study revealed a comprehensive aging-associated transcriptomic atlas characterizing the cell type-specific mechanisms during ovarian aging at the single-cell level and offers new diagnostic biomarkers and potential therapeutic targets for age-related goat ovarian diseases.

A Novel Bifunctional µOR Agonist and σ1R Antagonist with Potent Analgesic Responses and Reduced Adverse Effects.

Bifunctional ligands possessing both µOR agonism and σ1R antagonism have shown promise in producing strong analgesic effects with reduced opioid-related side effects. However, the µOR agonism activity of most dual ligands diminishes compared with classical opioids, raising concern about their effectiveness in managing nociceptive pain. In this study, a new class of dual µOR agonist/σ1R antagonist was reported. Through structure-activity relationship analyses, we identified the optimal compound, 4x, which displayed picomolar µOR agonism activity (EC50: 0.6 ± 0.2 nM) and good σ1R inhibitory activity (Ki: 363.7 ± 5.6 nM) with excellent selectivity. Compound 4x exhibited robust analgesic effects in various pain models, with significantly reduced side effects. Importantly, compound 4x also possessed good safety profiles and no abnormalities were observed in biological parameters even under a high dosage. Our findings suggest that 4x may be a promising lead compound for developing safer opioids and warrants further in-depth studies.

A Self-Healing Thermoset Epoxy Modulated by Dynamic Boronic Ester for Powder Coating.

Thermoset powder coatings exhibit distinctive characteristics such as remarkable hardness and exceptional resistance to corrosion. In contrast to conventional paints, powder coatings are environmentally friendly due to the absence of volatile organic compounds (VOCs). However, their irreversible cross-linking structures limit their chain segment mobility, preventing polymers from autonomously repairing cracks. Dynamic cross-linking networks have garnered attention for their remarkable self-healing capabilities, facilitated by rapid internal bond exchange. Herein, we introduce an innovative method for synthesizing thermoset epoxy containing boronic ester moieties which could prolong the life of the powder coating. The epoxy resin system relies on the incorporation of two curing agents: one featuring small-molecule diamines with boronic bonds and the other a modified polyurethane prepolymer. A state of equilibrium in mechanical properties was achieved via precise manipulation of the proportions of these agents, with the epoxy composite exhibiting a fracture stress of 67.95 MPa while maintaining a stable glass transition temperature (Tg) of 51.39 °C. This imparts remarkable self-healing ability to the coating surface, capable of returning to its original state even after undergoing 1000 cycles of rubbing (using 1200-grit abrasive paper). Furthermore, the introduction of carbon nanotube nanoparticles enabled non-contact sequential self-healing. Subsequently, we introduce this method into powder coatings of different materials. Therefore, this work provides a strategy to develop functional interior decoration and ensure its potential for broad-ranging applications, such as aerospace, transportation, and other fields.

Diet Is Associated with Frailty in Lung Cancer: A Possible Role of Gut Microbiota.

This study investigated the associations between diet and frailty in lung cancer patients and the potential role of the gut microbiota involved. We assessed dietary intake and frailty status in 231 lung cancer patients by 3-day, 24-h dietary recalls and Fried frailty criteria, respectively, and collected 50 fecal samples for next-generation sequencing. A total of 75 (32.5%) patients were frail, which might be related to significantly lower intake of energy, protein, carbohydrate, dietary fiber, niacin, leucine, some minerals, and a poorer dietary quality as indicated by the Chinese Healthy Eating Index (p < 0.05). Among these, carbohydrate (OR = 0.98; 95% CI 0.96-0.99; p = 0.010), calcium (OR = 0.99; 95% CI 0.99-1.00; p = 0.025), and selenium (OR = 1.03; 95% CI 1.00-1.06; p = 0.022) were all significantly associated with frailty. A multivariate logistic regression analysis showed that the mean risk of frailty was 0.94 times lower (95% CI 0.90-0.99; p = 0.009) among participants with higher CHEI scores. Additionally, the frail patients demonstrated significantly lower gut microbiota ß diversity (p = 0.001) and higher relative abundance of Actinobacteriota (p = 0.033). Frailty in lung cancer patients might be associated with insufficient nutrients intake and a poor dietary quality through gut microbiota regulation.

The Complex Network of ADP-Ribosylation and DNA Repair: Emerging Insights and Implications for Cancer Therapy.

ADP-ribosylation is a post-translational modification of proteins that plays a key role in various cellular processes, including DNA repair. Recently, significant progress has been made in understanding the mechanism and function of ADP-ribosylation in DNA repair. ADP-ribosylation can regulate the recruitment and activity of DNA repair proteins by facilitating protein-protein interactions and regulating protein conformations. Moreover, ADP-ribosylation can influence additional post-translational modifications (PTMs) of proteins involved in DNA repair, such as ubiquitination, methylation, acetylation, phosphorylation, and SUMOylation. The interaction between ADP-ribosylation and these additional PTMs can fine-tune the activity of DNA repair proteins and ensure the proper execution of the DNA repair process. In addition, PARP inhibitors have been developed as a promising cancer therapeutic strategy by exploiting the dependence of certain cancer types on the PARP-mediated DNA repair pathway. In this paper, we review the progress of ADP-ribosylation in DNA repair, discuss the crosstalk of ADP-ribosylation with additional PTMs in DNA repair, and summarize the progress of PARP inhibitors in cancer therapy.

Spatial Configuration Effects on the Dissociation between Active and Latent States in Visual Working Memory.

Visual working memory includes both active, recallable items and latent items not directly available for recall. During the online manipulation of active working memory, latent items gain robust retention. According to the dissociation account, active and passive memories exist in independent states, both of which take up their own cognitive resources. However, it is unclear whether dissociation is a universal phenomenon during memory maintenance. Given that memory information is retained as a binding of identity and location, the spatial proximity of memory items might shield the dissociation property. To test this, we adopted a retro-cue memory task where the cued and uncued items were separated in the active and latent states. In Experiment 1, the memory items were presented at a relatively large spatial distance. The results supported the dissociation account for well-separated items. However, Experiment 2 rejected the dissociation for closer-in items, possibly because items in visual working memory were spatially labeled. These findings suggest that while memory maintenance generally conforms to the dissociation account, the spatial configuration of memory items can affect the dissociation property between the active and latent neural states in visual working memory.