Inactivation efficacy and mechanism of 9.375 GHz electromagnetic wave on coronavirus.

Epidemics caused by pathogenic viruses are a severe threat to public health worldwide. Electromagnetic waves are a type of noncontact and nonionizing radiation technology that has emerged as an effective tool for inactivating bacterial pathogens. In this study, we used a 9.375 GHz electromagnetic wave to study the inactivation effect and mechanism of electromagnetic waves on MHV-A59, a substitute virus for pathogenic human coronavirus, and to evaluate the inactivation efficiency on different surface materials. We showed that 9.375 GHz electromagnetic waves inactivate MHV-A59 by destroying viral particles, envelopes, or genomes. We also found that 9.375 GHz electromagnetic waves can decrease the infectivity of viruses on the surface of inanimate materials such as plastic, glass, cloth, and wood. In conclusion, our results suggested that the 9.375 GHz electromagnetic wave is a promising disinfection technique for preventing the spread and infection of pathogenic viruses.

Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosis.

Allogeneic chimeric antigen receptor (CAR)-T cells hold great promise for expanding the accessibility of CAR-T therapy, whereas the risks of allograft rejection have hampered its application. Here, we genetically engineered healthy-donor-derived, CD19-targeting CAR-T cells using CRISPR-Cas9 to address the issue of immune rejection and treated one patient with refractory immune-mediated necrotizing myopathy and two patients with diffuse cutaneous systemic sclerosis with these cells. This study was registered at ClinicalTrials.gov (NCT05859997). The infused cells persisted for over 3 months, achieving complete B cell depletion within 2 weeks of treatment. During the 6-month follow-up, we observed deep remission without cytokine release syndrome or other serious adverse events in all three patients, primarily shown by the significant improvement in the clinical response index scores for the two diseases, respectively, and supported by the observations of reversal of inflammation and fibrosis. Our results demonstrate the high safety and promising immune modulatory effect of the off-the-shelf CAR-T cells in treating severe refractory autoimmune diseases.

Risk prediction models for intensive care unit-acquired weakness in critically ill patients: A systematic review.

BACKGROUND: Intensive care unit (ICU)-acquired weakness (ICU-AW) is a critical complication that significantly worsens patient prognosis. It is widely thought that risk prediction models can be harnessed to guide preventive interventions. While the number of ICU-AW risk prediction models is increasing, the quality and applicability of these models in clinical practice remain unclear. OBJECTIVE: The objective of this study was to systematically review published studies on risk prediction models for ICU-AW. METHODS: We searched electronic databases (PubMed, Web of Science, The Cochrane Library, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), China National Knowledge Infrastructure (CNKI), China Science and Technology Periodical Database (VIP), and Wanfang Database) from inception to October 2023 for studies on ICU-AW risk prediction models. Two independent researchers screened the literature, extracted data, and assessed the risk of bias and applicability of the included studies. RESULTS: A total of 2709 articles were identified. After screening, 25 articles were selected, encompassing 25 risk prediction models. The area under the curve for these models ranged from 0.681 to 0.926. Evaluation of bias risk indicated that all included models exhibited a high risk of bias, with three models demonstrating poor applicability. The top five predictors among these models were mechanical ventilation duration, age, Acute Physiology and Chronic Health Evaluation II score, blood lactate levels, and the length of ICU stay. The combined area under the curve of the ten validation models was 0.83 (95% confidence interval: 0.77-0.88), indicating a strong discriminative ability. CONCLUSIONS: Overall, ICU-AW risk prediction models demonstrate promising discriminative ability. However, further optimisation is needed to address limitations, including data source heterogeneity, potential biases in study design, and the need for robust statistical validation. Future efforts should prioritise external validation of existing models or the development of high-quality predictive models with superior performance. REGISTRATION: The protocol for this study is registered with the International Prospective Register of Systematic Reviews (registration number: CRD42023453187).

Asymmetric Organocatalytic 1,3-Dipolar Cycloaddition of Azomethine Ylides with ß-Substituted Cyclic Enones.

The enantioselective and diastereoselective control of 1,3-dipolar cycloaddition reactions to ß-substituted cyclic enones has been developed. The 1,3-dipolar cycloaddition of phthalazinium dicyanomethanides with cyclic dienones affords chiral tetrahydropyrrolo[2,1-a]phthalazine derivatives 3 through vinylogous iminium ion activation by combining a cinchona-based primary amine C3 and a chiral camphorsulfonic acid additive. Conversely, with a weaker 3,5-bis(trifluoromethyl)benzoic acid additive, the 1,3-dipolar cycloaddition of phthalazinium dicyanomethanides with ß-substituted cyclic enones leads to chiral hexahydroisoindolo[1,2-a]phthalazin-10(8H)-one derivatives 4 with excellent stereocontrol via endo-dienamine activation.

RNF31-mediated IKKα ubiquitination aggravates inflammation and intestinal injury through regulating NF-κB activation in human and mouse neonates.

AIMS: Neonatal necrotizing enterocolitis (NEC) is a leading cause of intestine inflammatory disease, and macrophage is significantly activated during NEC development. Posttranslational modifications (PTMs) of proteins, particularly ubiquitination, play critical roles in immune response. This study aimed to investigate the effects of ubiquitin-modified proteins on macrophage activation and NEC, and discover novel NEC-related inflammatory proteins. MATERIALS AND METHODS: Proteomic and ubiquitin proteomic analyses of intestinal macrophages in NEC/healthy mouse pups were carried out. In vitro macrophage inflammation model and in vivo NEC mouse model, as well as clinical human samples were used for further verification the inhibitor of nuclear factor-κB kinase α (IKKα) ubiquitination on NEC development through Western blot, immunofluorescence, quantitative real-time polymerase chain reaction (qRT-PCR) and flow cytometry. KEY FINDINGS: We report here that IKKα was a new ubiquitin-modified protein during NEC through ubiquitin proteomics, and RING finger protein 31 (RNF31) acted as an E3 ligase to be involved in IKKα degradation. Inhibition of IKKα ubiquitination and degradation with siRNF31 or proteasome inhibitor decreased nuclear factor-κB (NF-κB) activation, thereby decreasing the expression of pro-inflammatory factors and M1 macrophage polarization, resulting in reliving the severity of NEC. SIGNIFICANCE: Our study suggests the activation of RNF31-IKKα-NF-κB axis triggering NEC development and suppressing RNF31-mediated IKKα degradation may be therapeutic strategies to be developed for NEC treatment.

Predictors of post-healing recurrence in patients with diabetic foot ulcers: A systematic review and meta-analysis.

BACKGROUND: Diabetic foot ulcer is one of the most prevalent, serious, and costly consequences of diabetes, often associated with peripheral neuropathy and peripheral arterial disease. These ulcers contribute to high disability and mortality rates in patients and pose a major challenge to clinical management. OBJECTIVE: To systematically review the risk prediction models for post-healing recurrence in diabetic foot ulcer (DFU) patients, so as to provide a reference for clinical staff to choose appropriate prediction models. METHODS: The authors searched five databases (Cochrane Library, PubMed, Web of Science, EMBASE, and Chinese Biomedical Database) from their inception to September 23, 2023, for relevant literature. After data extraction, the quality of the literature was evaluated using the Predictive Model Research Bias Risk and Suitability Assessment tool (PROBAST). Meta-analysis was performed using STATA 17.0 software. RESULTS: A total of 9 studies involving 5956 patients were included. The recurrence rate after DFU healing ranged from 6.2 % to 41.4 %. Nine studies established 15 risk prediction models, and the area under the curve (AUC) ranged from 0.660 to 0.940, of which 12 models had an AUC≥0.7, indicating good prediction performance. The combined AUC value of the 9 validation models was 0.83 (95 % confidence interval: 0.79-0.88). Hosmer-Lemeshow test was performed for 10 models, external validation for 5 models, and internal validation for 6 models. Meta-analysis showed that 14 predictors, such as age and living alone, could predict post-healing recurrence in DFU patients (p < 0.05). CONCLUSION: To enhance the quality of these risk prediction models, there is potential for future improvements in terms of follow-up duration, model calibration, and validation processes.

[Notch1/Akt/Foxo1 Pathway Regulated by Kisspeptin Is Involved in Endometrial Decidualization in Patients With Recurrent Spontaneous Abortion]. / kisspeptin调控Notch1/Akt/Foxo1é€šè·¯å‚ä¸Žå¤å‘æ€§æµäº§æ‚£è€ å­å®«å† è†œèœ•è†œåŒ–.

Objective: Kisspeptin, a protein encoded by the KISS1 gene, functions as an essential factor in suppressing tumor growth. The intricate orchestration of cellular processes such as proliferation and differentiation is governed by the Notch1/Akt/Foxo1 signaling pathway, which assumes a central role in maintaining cellular homeostasis. In the specific context of this investigation, the focal point lies in a meticulous exploration of the intricate mechanisms underlying the regulatory effect of kisspeptin on the process of endometrial decidualization. This investigation delves into the interplay between kisspeptin and the Notch1/Akt/Foxo1 signaling pathway, aiming to elucidate its significance in the pathophysiology of recurrent spontaneous abortion (RSA). Methods: We enrolled a cohort comprising 45 individuals diagnosed with RSA, who were admitted to the outpatient clinic of the Reproductive Center at the Second Affiliated Hospital of Soochow University between June 2020 and December 2020. On the other hand, an additional group of 50 women undergoing elective abortion at the outpatient clinic of the Family Planning Department during the same timeframe was also included. To comprehensively assess the molecular landscape, Western blot and RT-qPCR were performed to analyze the expression levels of kisspeptin (and its gene KISS1), IGFBP1 (an established marker of decidualization), Notch1, Akt, and Foxo1 within the decidua. Human endometrial stromal cells (hESC) were given targeted interventions, including treatment with siRNA to disrupt KISS1 or exposure to kisspeptin10 (the bioactive fragment of kisspeptin), and were subsequently designated as the siKP group or the KP10 group, respectively. A control group comprised hESC was transfected with blank siRNA, and cell proliferation was meticulously evaluated with CCK8 assay. Following in vitro induction for decidualization across the three experimental groups, immunofluorescence assay was performed to identify differences in Notch1 expression and decidualization morphology between the siKP and the KP10 groups. Furthermore, RT-qPCR and Western blot were performed to gauge the expression levels of IGFBP1, Notch1, Akt, and Foxo1 across the three cell groups. Subsequently, decidualization was induced in hESC by adding inhibitors targeting Notch1, Akt, and Foxo1. The expression profiles of the aforementioned proteins and genes in the four groups were then examined, with hESC induced for decidualization without adding inhibitors serving as the normal control group. To establish murine models of normal pregnancy (NP) and RSA, CBA/J×BALB/c and CBA/J×DBA/2 mice were used. The mice were respectively labeled as the NP model and RSA model. The experimental groups received intraperitoneal injections of kisspeptin10 and kisspeptin234 (acting as a blocker) and were designated as RSA-KP10 and NP-KP234 groups. On the other hand, the control groups received intraperitoneal injections of normal saline (NS) and were referred to as RSA-NS and NP-NS groups. Each group comprised 6 mice, and uterine tissues from embryos at 9.5 days of gestation were meticulously collected for observation of embryo absorption and examination of the expression of the aforementioned proteins and genes. Results: The analysis revealed that the expression levels of kisspeptin, IGFBP1, Notch1, Akt, and Foxo1 were significantly lower in patients diagnosed with RSA compared to those in women with NP (P<0.01 for kisspeptin and P<0.05 for IGFBP1, Notch1, Akt, and Foxo1). After the introduction of kisspeptin10 to hESC, there was an observed enhancement in decidualization capability. Subsequently, the expression levels of Notch1, Akt, and Foxo1 showed an increase, but they decreased after interference with KISS1. Through immunofluorescence analysis, it was observed that proliferative hESC displayed a slender morphology, but they transitioned to a rounder and larger morphology post-decidualization. Concurrently, the expression of Notch1 increased, suggesting enhanced decidualization upon the administration of kisspeptin10, but the expression decreased after interference with KISS1. Further experimentation involved treating hESC with inhibitors specific to Notch1, Akt, and Foxo1 separately, revealing a regulatory sequence of Notch1/Akt/Foxo1 (P<0.05). In comparison to the NS group, NP mice administered with kisspeptin234 exhibited increased fetal absorption rates (P<0.001) and decreased expression of IGFBP1, Notch1, Akt, and Foxo1 (P<0.05). Conversely, RSA mice administered with kisspeptin10 demonstrated decreased fetal absorption rates (P<0.001) and increased expression levels of the aforementioned molecules (P<0.05). Conclusion: It is suggested that kisspeptin might exert its regulatory influence on the process of decidualization through the modulation of the Notch1/Akt/Foxo1 signaling cascade. A down-regulation of the expression levels of kisspeptin could result in suboptimal decidualization, which in turn might contribute to the development or progression of RSA.

Socioeconomic disparity in the natural history of cutaneous melanoma: evidence from two large prospective cohorts.

BACKGROUND: Previous studies on the associations between socioeconomic status (SES) and cutaneous malignant melanoma (CMM) failed to distinguish the effects of different SES factors under an individual-data-based prospective study design. METHODS: Based on UK Biobank (UKB) and China Kadoorie Biobank (CKB), we estimated the effects of four SES factors on transitions from baseline to CMM in situ, subsequently to invasive CMM and further CMM mortality by applying multistate models. We further explored to which extent the associations between SES and CMM incidence could be explained by potential mediators including sun exposure, lifestyle and ageing in UKB. RESULTS: In multistate analyses, good household income was independently associated with an increased risk of CMM in situ (HR=1.38, 95% CI: 1.21 to 1.58) and invasive CMM (HR=1.34, 95% CI: 1.22 to 1.48) in UKB. These findings were partly validated in CKB. Especially in UKB, we observed an increased risk of CMM in situ and invasive CMM among participants with good type of house; only good education was independently associated with lower risk of evolving to invasive CMM among patients with CMM in situ (HR=0.69, 95% CI: 0.52 to 0.92); only good household income was independently associated with lower risk of CMM mortality among patients with CMM (HR=0.65, 95% CI: 0.45 to 0.95). In mediation analysis, the proportions attributable to the mediating effect were <6% for all selected variables, including self-reported sun exposure-related factors. CONCLUSION: SES factors have different effects on the incidence and progression of CMM. The association between SES and incident CMM is neither causal nor well explained by selected mediators.

Multiplex influences on vigilance and biochemical variables induced by sleep deprivation.

Introduction: Sleep loss and sleep deprivation (SD) cause deleterious influences on health, cognition, mood and behaviour. Nevertheless, insufficient sleep and SD are prevalent across many industries and occur in various emergencies. The deleterious consequences of SD have yet to be fully elucidated. This study aimed to assess the extensive influences of SD on physiology, vigilance, and plasma biochemical variables. Methods: Seventeen volunteers were recruited to participate in a 32.5-h SD experiment. Multiple physiological and cognitive variables, including tympanic temperature, blood oxygen saturation (SaO2), and vigilance were recorded. Urinal/salivary samples were collected and subjected to cortisol or cortisone analysis, and plasma samples were subjected to transcriptomic analysis of circular RNA (circRNA) expression using microarray. Plasma neurotransmitters were measured by targeted metabolic analysis, and the levels of inflammatory factors were assessed by antibody microarray. Results: The volunteers showed significantly increased sleepiness and decreased vigilance during SD, and the changes in circadian rhythm and plasma biochemistry were observed. The plasma calcium (p = 0.0007) was induced by SD, while ischaemia-modified albumin (IMA, p = 0.0030) and total bile acid (TBA, p = 0.0157) decreased. Differentially expressed circRNAs in plasma were identified, which are involved in multiple signaling pathways including neuronal regulation and immunity. Accordingly, SD induced a decrease in 3-hydroxybutyric acid (3OBH, p = 0.0002) and an increase in thyroxine (T4, p < 0.0001) in plasma. The plasma anti-inflammatory cytokine IL-10 was downregulated while other ten inflammatory factors were upregulated. Conclusion: This study demonstrates that SD influences biochemical, physiological, cognitive variables, and the significantly changed variables may serve as candidates of SD markers. These findings may further our understanding of the detrimental consequence of sleep disturbance at multiple levels.

Generation of High-Affinity Aptamers for Indazole Synthetic Cannabinoids.

Synthetic cannabinoids are a widely abused class of dangerous psychoactive substances, especially among youths and young adults. Dozens of such drugs have been identified to date, and new ones continue to emerge. The ability to detect these drugs is important for interdiction efforts and the diagnosis of drug overdose, but existing analytical methods lack broad cross-reactivity to diverse members of this drug family. Here, we have utilized library-immobilized SELEX to generate DNA aptamers that can broadly recognize various members of the indazole-3-carboxamide synthetic cannabinoid family. Using two representatives of this family, AB-FUBINACA and 5F-AMB, we identify two aptamers FUB4 and AMB2F with respective dissociation constants (KDs) of 138 ± 15 and 411 ± 20 nM for their targets. These aptamers can recognize many indazole-based synthetic cannabinoids with high affinity and excellent specificity against natural cannabinoids as well as other structurally similar interferents like serotonin and tryptophan. We use these two aptamers to develop fluorescence strand-displacement sensors that successfully detect these synthetic cannabinoids at concentrations as low as 50 nM in human serum. The sensors can also detect up to 14 different drugs from this family─a major improvement over the six recognized by an existing commercial immunoassay.

Mutant IDH1 inhibition induces dsDNA sensing to activate tumor immunity.

Isocitrate dehydrogenase 1 (IDH1) is the most commonly mutated metabolic gene across human cancers. Mutant IDH1 (mIDH1) generates the oncometabolite (R)-2-hydroxyglutarate, disrupting enzymes involved in epigenetics and other processes. A hallmark of IDH1-mutant solid tumors is T cell exclusion, whereas mIDH1 inhibition in preclinical models restores antitumor immunity. Here, we define a cell-autonomous mechanism of mIDH1-driven immune evasion. IDH1-mutant solid tumors show selective hypermethylation and silencing of the cytoplasmic double-stranded DNA (dsDNA) sensor CGAS, compromising innate immune signaling. mIDH1 inhibition restores DNA demethylation, derepressing CGAS and transposable element (TE) subclasses. dsDNA produced by TE-reverse transcriptase (TE-RT) activates cGAS, triggering viral mimicry and stimulating antitumor immunity. In summary, we demonstrate that mIDH1 epigenetically suppresses innate immunity and link endogenous RT activity to the mechanism of action of a US Food and Drug Administration-approved oncology drug.

Macrophage α7nAChR alleviates the inflammation of neonatal necrotizing enterocolitis through mTOR/NLRP3/IL-1ß pathway.

BACKGROUND: Neonatal necrotizing enterocolitis (NEC) is one of the most prevalent and severe intestinal emergencies in newborns. The inflammatory activation of macrophages is associated with the intestinal injury of NEC. The neuroimmune regulation mediated by α7 nicotinic acetylcholine receptor (α7nAChR) plays an important role in regulating macrophage activation and inflammation progression, but in NEC remains unclear. This study aims to explore the effect of macrophage α7nAChR on NEC. METHODS: Mice NEC model were conducted with high-osmolarity formula feeding, hypoxia, and cold stimulation. The α7nAChR agonist PNU-282987 and mTOR inhibitor rapamycin were treated by intraperitoneal injections in mice. The expression and distribution of macrophages, α7nAChR, and phospho-mammalian target of rapamycin (p-mTOR) in the intestines of NEC patients and mice was assessed using immunohistochemistry, immunofluorescence, and flow cytometry. The expression of NLRP3, activated caspase-1 and IL-1ß in mice intestines was detected by flow cytometry, western blot or ELISA. In vitro, the mouse RAW264.7 macrophage cell line was also cultured followed by various treatments. Expression of p-mTOR, NLRP3, activated caspase-1, and IL-1ß in macrophages was determined. RESULTS: Macrophages accumulated in the intestines and the expression of α7nAChR in the mucosal and submucosal layers of the intestines was increased in both the NEC patients and mice. The p-mTOR and CD68 were increased and co-localized in intestines of NEC patients. In vitro, α7nAChR agonist PNU-282987 significantly reduced the increase of NLRP3, activated caspase-1, and IL-1ß in macrophages. PNU-282987 also significantly reduced the increase of p-mTOR. The effect was blocked by AMPK inhibitor compound C. The expression of NLRP3, activated caspase-1, and IL-1ß was inhibited after mTOR inhibitor rapamycin treatment. In NEC model mice, PNU-282987 reduced the expression of p-mTOR, NLRP3, activated caspase-1, and IL-1ß in the intestine. Meanwhile, rapamycin significantly attenuated NLRP3 activation and the release of IL-1ß. Moreover, the proportion of intestinal macrophages and intestinal injury decreased after PNU-282987 treatment. CONCLUSION: Macrophage α7nAChR activation mitigates NLRP3 inflammasome activation by modulating mTOR phosphorylation, and subsequently alleviates intestinal inflammation and injury in NEC.

Combined effects of microplastics and pharmaceutical and personal care products on algae: A critical review.

Microplastics (MPs) and pharmaceuticals and personal care products (PPCPs) are ubiquitous in aquatic environments. Algae play an important role in aquatic environments. Thus, it is important to study the response of algae to combined exposure of MPs and PPCPs. Here, we review the effects of MPs and PPCPs on algae. First, the individual effects of MPs and PPCPs on algae were summarized. Second, the combined effects of MPs and PPCPs on algae were systematically analyzed. (1) Antagonism: ① when the MPs are too large to enter the algal cells, the adsorption of PPCPs onto MPs results in decreased the contact of MPs and PPCPs with algae; ② PPCPs and MPs have opposing actions on the same biological target; ③ MPs increase the activity of metabolic enzymes in algae, thus promoting the PPCP degradation. (2) Synergy: ① when the MPs are small enough to enter algal cells, the adsorption of PPCPs on MPs promotes the entry of PPCPs; ② when MPs are negatively charged, the adsorption of positively charged PPCPs by MPs decreases the electrostatic repulsion, increasing the interaction between algae and MPs; ③ complementary modes of action between MPs and PPCPs show combined effects on the same biological target. Third, the relative importance of the factors that impact the combined effects are evaluated using the random forest model decreased in the following order: PPCP types > algal species > MP size > MP concentration > MP types > exposure time. Finally, future directions for the combined effects of MPs and PPCPs are proposed, which will facilitate a better understanding of the environmental fate and risks of both MPs and PPCPs.

Dynamics of polarization-tuned mirror symmetry breaking in a rotationally symmetric system.

Lateral momentum conservation is typically kept in a non-absorptive rotationally symmetric system through mirror symmetry via Noether's theorem when illuminated by a homogeneous light wave. Therefore, it is still very challenging to break the mirror symmetry and generate a lateral optical force (LOF) in the rotationally symmetric system. Here, we report a general dynamic action in the SO(2) rotationally symmetric system, originating from the polarization-tuned mirror symmetry breaking (MSB) of the light scattering. We demonstrate theoretically and experimentally that MSB can be generally applied to the SO(2) rotationally symmetric system and tuned sinusoidally by polarization orientation, leading to a highly tunable and highly efficient LOF (9.22 pN/mW/µm-2) perpendicular to the propagation direction. The proposed MSB mechanism and LOF not only complete the sets of MSB of light-matter interaction and non-conservative force only using a plane wave but also provide extra polarization manipulation freedom.

Associations of sugar intake, high-sugar dietary pattern, and the risk of dementia: a prospective cohort study of 210,832 participants.

BACKGROUND: Limited evidence demonstrated the potential relationship between dietary sugar intake and dementia. This association demands further clarification in a large-scale population. METHODS: A total of 210,832 participants from the UK Biobank cohort were included in this prospective cohort study. Absolute and relative sugar intake and high-sugar dietary scores were utilized to reflect dietary sugar intake. Absolute sugar intake was identified by the Oxford WebQ in the UK Biobank. Relative sugar intake was calculated by dividing the absolute sugar intake by total diet energy. High-sugar dietary pattern was identified using the method of reduced rank regression. Cox proportional hazards regression analyses and restricted cubic splines were performed to examine the longitudinal associations between dietary sugar intake and all-cause dementia and its main subtype, Alzheimer's disease. Explorative mediation analyses were conducted to explore underlying mechanisms. RESULTS: Increased absolute sugar intake (g/day) was significantly associated with a higher risk of all-cause dementia (HR = 1.003, [95%CI: 1.002-1.004], p < 0.001) and Alzheimer's disease (1.002, [1.001-1.004], 0.005). Relative sugar intake (%g/kJ/day) also demonstrated significant associations with all-cause dementia (1.317, [1.173-1.480], p < 0.001) and Alzheimer's disease (1.249, [1.041-1.500], 0.017), while the high-sugar dietary score was only significantly associated with a higher risk of all-cause dementia (1.090, [1.045-1.136], p < 0.001). In addition, both sugar intake and high-sugar dietary score demonstrated significant non-linear relationships with all-cause dementia and Alzheimer's disease (all p values for non-linearity < 0.05). CONCLUSIONS: Our study provided evidence that excessive sugar intake was associated with dementia. Controlling the excess consumption of dietary sugar may be of great public health implications for preventing dementia.

CAR-T cell combination therapies in hematologic malignancies.

Chimeric antigen receptor-T cell therapy, a groundbreaking cancer treatment, has achieved remarkable success against hematologic malignancies. However, CAR-T monotherapy faces challenges in certain cases, including treatment tolerance and relapse rates. To overcome these challenges, researchers are investigating combining CAR-T cells with other treatments to enhance therapeutic efficacy. Therefore, this review aims to investigate the progress of research in combining CAR-T cells for hematologic malignancies. It covers the basic principles and clinical applications of CAR-T cell therapy, detailing combinations with chemotherapy, immune checkpoint inhibitors, targeted drugs, radiotherapy, hematopoietic stem cell transplantation, and other treatments. These combinations synergistically enhance the antitumor effects of CAR-T cells and comprehensively target tumors through different mechanisms, improving patient response and survival rates.

Mitochondrial­associated endoplasmic reticulum membrane interference in ovarian cancer (Review).

The mitochondria­associated endoplasmic reticulum (ER) membrane (MAM), serving as a vital link between the mitochondria and ER, holds a pivotal role in maintaining the physiological function of these two organelles. Its specific functions encompass the participation in the biosynthesis and functional regulation of the mitochondria, calcium ion transport, lipid metabolism, oxidative stress and autophagy among numerous other facets. Scientific exploration has revealed that MAMs hold potential as effective therapeutic targets influencing the mitochondria and ER within the context of cancer therapy. The present review focused on elucidating the related pathways of mitochondrial autophagy and ER stress and their practical application in ovarian cancer, aiming to identify commonalities existing between MAMs and these pathways, thereby extending to related applications of MAMs in ovarian cancer treatment. This endeavor aimed at exploring new potential for MAMs in clinically managing ovarian cancer.

Role of hydrogen sulfide in dermatological diseases.

Hydrogen sulfide (H2S), together with carbon monoxide (CO) and nitric oxide (NO), is recognized as a vital gasotransmitter. H2S is biosynthesized by enzymatic pathways in the skin and exerts significant physiological effects on a variety of biological processes, such as apoptosis, modulation of inflammation, cellular proliferation, and regulation of vasodilation. As a major health problem, dermatological diseases affect a large proportion of the population every day. It is urgent to design and develop effective drugs to deal with dermatological diseases. Dermatological diseases can arise from a multitude of etiologies, including neoplastic growth, infectious agents, and inflammatory processes. The abnormal metabolism of H2S is associated with many dermatological diseases, such as melanoma, fibrotic diseases, and psoriasis, suggesting its therapeutic potential in the treatment of these diseases. In addition, therapies based on H2S donors are being developed to treat some of these conditions. In the review, we discuss recent advances in the function of H2S in normal skin, the role of altering H2S metabolism in dermatological diseases, and the therapeutic potential of diverse H2S donors for the treatment of dermatological diseases.

Updates of primary central nervous system lymphoma.

Lymphoma occurring in the central nervous system is considered primary central nervous system lymphoma (PCNSL), usually without systematic lesions. Over the last few decades, a deep understanding of PCNSL has been lacking due to the low incidence rate, and the overall survival and progression-free survival of patients with PCNSL are lower than those with other types of non-Hodgkin lymphoma. Recently, there have been several advancements in research on PCNSL. Advances in diagnosis of the disease are primarily reflected in the promising diagnostic efficiency of novel biomarkers. Pathogenesis mainly involves abnormal activation of nuclear factor kappa-B signaling pathways, copy number variations, and DNA methylation. Novel therapies such as Bruton's tyrosine kinase inhibitors, immunomodulatory drugs, immune checkpoint inhibitors, and phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors are being evaluated as possible treatment options for PCNSL, especially for relapsed/refractory (R/R) cases. Several clinical trials also indicated the promising feasibility and efficacy of chimeric antigen receptor T-cell therapy for selected R/R PCNSL patients. This review focuses on discussing recent updates, including the diagnosis, pathogenesis, and novel therapy of PCNSL.