Association between frailty and acute kidney injury after cardiac surgery: unraveling the moderation effect of body fat through an international, retrospective, multi-cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication after cardiac surgery that significantly affects patient outcomes. Given the limited treatment options available, identifying modifiable risk factors is critical. Frailty and obesity, two heterogeneous physiological states, have significant implications for identifying and preventing AKI. Our study investigated the interplay among frailty, body composition, and AKI risk after cardiac surgery to inform patient management strategies. MATERIAL AND METHODS: This retrospective cohort study included three international cohorts. Primary analysis was conducted in adult patients who underwent cardiac surgery between 2014 and 2019 at Wuhan XX Hospital, China. We tested the generalizability of our findings with data from two independent international cohorts, the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU Collaborative Research Database. Frailty was assessed using a clinical lab-based frailty index (FI-LAB), while total body fat percentage (BF%) was calculated based on a formula accounting for BMI, sex, and age. Logistic regression models were used to analyze the associations between frailty, body fat, and AKI, adjusting for pertinent covariates. RESULTS: A total of 8785 patients across three international cohorts were included in the study. In the primary analysis of 3,569 patients from Wuhan XX Hospital, moderate and severe frailty were associated with an increased AKI risk after cardiac surgery. Moreover, a nonlinear relationship was observed between body fat percentage and AKI risk. When stratified by the degree of frailty, lower body fat correlated with a decreased incidence of AKI. Extended analyses using the MIMIC-IV and eICU cohorts (n=3,951 and n=1,265, respectively) validated these findings and demonstrated that a lower total BF% was associated with decreased AKI incidence. Moderation analysis revealed that the effect of frailty on AKI risk was moderated by the body fat percentage. Sensitivity analyses demonstrated results consistent with the main analyses. CONCLUSION: Higher degrees of frailty were associated with an elevated risk of AKI following cardiac surgery, and total BF% moderated this relationship. This research underscores the significance of integrating frailty and body fat assessments into routine cardiovascular care to identify high-risk patients for AKI and implement personalized interventions to improve patient outcomes.

Abnormal HCK/glutamine/autophagy axis promotes endometriosis development by impairing macrophage phagocytosis.

The presence of extensive infiltrated macrophages with impaired phagocytosis is widely recognised as a significant regulator for the development of endometriosis (EMs). Nevertheless, the metabolic characteristics and the fundamental mechanism of impaired macrophage phagocytosis are yet to be clarified. Here, we observe that there is the decreased expression of haematopoietic cellular kinase (HCK) in macrophage of peritoneal fluid from EMs patients, which might be attributed to high oestrogen and hypoxia condition. Of note, HCK deficiency resulted in impaired macrophage phagocytosis, and increased number and weight of ectopic lesions in vitro and in vivo. Mechanistically, this process was mediated via regulation of glutamine metabolism, and further upregulation of macrophage autophagy in a c-FOS/c-JUN dependent manner. Additionally, macrophages of EMs patients displayed insufficient HCK, excessive autophagy and phagocytosis dysfunction. In therapeutic studies, supplementation with glutamine-pre-treated macrophage or Bafilomycin A1 (an autophagy inhibitor)-pre-treated macrophage leads to the induction of macrophage phagocytosis and suppression of EMs development. This observation reveals that the aberrant HCK-glutamine-autophagy axis results in phagocytosis obstacle of macrophage and further increase the development risk of Ems. Additionally, it offers potential therapeutic approaches to prevent EMs, especially patients with insufficient HCK and macrophage phagocytosis dysfunction.

Aliphatic Hydrosilanes via Nickel-Catalyzed Reductive Csp3-Si Coupling of Primary Alkyl Bromides and Chlorohydrosilanes.

The reductive C-Si coupling of chlorosilanes offers efficient access to organosilanes, but its potential for constructing aliphatic ones remains largely unexplored. This manuscript presents a nickel-catalyzed Csp3-Si coupling reaction of unactivated alkyl-Br and R2Si(H)Cl. This work establishes a new approach for synthesizing highly functionalized aliphatic hydrosilanes from readily available chemical feedstocks. The reaction is easily scalable and can accommodate various functional groups, including carboxylic acids, which are usually incompatible with basic conditions.

A Mechanistic Analysis of Metformin's Biphasic Effects on Lifespan and Healthspan in C. elegans: Elixir in Youth, Poison in Elder.

Aging, a complex biological process influenced by genetic, environmental, and pharmacological factors, presents a significant challenge in understanding its underlying mechanisms. In this study, we explored the divergent impacts of metformin treatment on the lifespan and healthspan of young and old C. elegans, demonstrating a intriguing "elixir in youth, poison in elder" phenomenon. By scrutinizing the gene expression changes in response to metformin in young (day 1 of adulthood) and old (days 8) groups, we identified nhr-57 and C46G7.1 as potential modulators of age-specific responses. Notably, nhr-57 and C46G7.1 exhibit contrasting regulation patterns, being up-regulated in young worms but down-regulated in old counterparts following metformin treatment. Functional studies employing knockdown approaches targeting nhr-57, a gene under the control of hif-1 with a documented protective function against pore-forming toxins in C. elegans, and C46G7.1, unveiled their critical roles in modulating lifespan and healthspan, as well as in mediating the biphasic effects of metformin. Furthermore, deletion of hif-1 retarded the influence of metformin, implicating the involvement of hif-1/nhr-57 in age-specific drug responses. These findings underscored the necessity of deciphering the mechanisms governing age-related susceptibility to pharmacological agents to tailor interventions for promoting successful aging.

The Applicability of Polyetheretherketone and Titanium Mesh in Cranioplasty: A Retrospective Comparative Analysis.

OBJECTIVE: To compare the clinical application effect and safety of polyetheretherketone (PEEK) and titanium mesh (TM) in cranioplasty. METHODS: Four-year retrospective comparison of patients (96 cases) undergoing synthetic cranioplasty with PEEK or TM. The patients were divided into the PEEK group (24 cases) and the TM group (72 cases) according to the implants, and the patient demographics, general conditions before the operation, postoperative complications, length of postoperative hospital stay, total costs, satisfaction with shaping and long-term complications were compared between the 2 groups. RESULTS: Patients in the PEEK group were younger than those in the TM group (P=0.019). Hospitalization costs were significantly higher in the PEEK group than in the TM group (P<0.001). The incidence of postoperative subcutaneous effusion was 33% in the PEEK group and 6.9% in the TM group, which suggests that patients in the PEEK group had a higher risk of postoperative subcutaneous effusion (P=0.001). There was no significant difference in the incidence of long-term complications and cosmetic satisfaction between the 2 groups at 4 years postoperatively. CONCLUSIONS: In this study, both titanium mesh and PEEK are reliable implants for cranioplasty. Titanium mesh is widely used in cranioplasty due to its cost-effective performance. PEEK has gradually gained recognition due to the characteristics of the material and surgical procedure, but the price needs to be further reduced, and attention should be paid to the occurrence and treatment of early postoperative subcutaneous effusion.

Corrigendum to "Nutrient composition and functional constituents of daylily from different producing areas based on widely targeted metabolomics" [Food Chemistry: X Nutrient composition and functional constituents of daylily from different producing areas based on widely targeted metabolomics 21 (2024) 101239/FOCHX-D-23-01093].

[This corrects the article DOI: 10.1016/j.fochx.2024.101239.].

Penicianstinoids F-K, six undescribed meroterpenoids from the marine algicolous fungus Penicillium sp. RR-DL-1-7.

Six previously undescribed meroterpenoids, penicianstinoids F-K (1-6), together with four known analogues, dehydroaustinol (7), dehydroaustin (8), penicianstinoid A (9), and furanoaustinol (10), were isolated from the cultures of the algicolous fungus Penicillium sp. RR-DL-1-7, derived from the red alga Rhodomela confervoides. Their structures and relative configuration were established by detailed spectroscopic analysis of NMR and HR-MS experiments, and the absolute configurations were assigned by X-ray diffraction and ECD spectral analysis. None of the isolates showed obvious growth inhibitory effects against five plankton and four bacteria species tested.

Replacement of sedentary behavior with various physical activities and the risk of incident depression: a prospective analysis of accelerator-measured and self-reported UK Biobank data.

PURPOSE: To examine the dose‒response relationships of sedentary behavior (SB) and physical activities (PAs) with depression, and to explore the effects of replacing SB with PAs on depression risk. METHODS: The study used data from UK Biobank aged 37 to 73 years. Light physical activity (LPA), moderate-to-vigorous activity (MVPA), sleep duration, and total sedentary behavior (TSB) were measured by accelerometers. Self-reported SB was also adopted when daily screen-sedentary behavior time (SSB) and leisure-sedentary behavior time (LSB) were the focus. Incident depression was obtained from the part of mental and behavioral disorders in the "first occurrence fields" of UK Biobank. A Cox proportional hazard model and isotemporal substitution model were performed to explore the associations of LPA, MVPA, TSB, LSB, SSB, and sleep on depression and the effects of replacing SB time with equal PA time. RESULTS: Highest levels of MVPA (HR = 0.58, 95%CI: 0.50-0.68) were associated with decreased depression risk compared with the lowest level (Q1). Longer SSB time (HR = 1.18, 95%CI: 1.06-1.32), LSB time (HR = 1.19, 95%CI: 1.07-1.32), and TSB time (HR = 1.17, 95%CI: 1.00-1.38) could increase depression risk significantly. Replacing 1h/day TSB, SSB, and LSB with MVPA brought the greatest risk reductions [31% (HR = 0.69, 95%CI: 0.62-0.77), 30% (HR = 0.70, 95%CI: 0.65-0.77), and 29% (HR = 0.71, 95%CI: 0.65-0.77)]. Under the same conditions, the effects of LPA replacement were also significant, but weaker than those of MVPA. Subgroup analyses showed that replacing 1h/d TSB with LPA could significantly decrease the depression risk for the females, but not for the males. CONCLUSION: Large benefits for reducing the risk of incident depression could be attained by replacing a period of TSB, SSB, or LSB with equal PA time, especially for MVPA. Regular PA and less SB were recommended for improving mental health.

[Study on the value of systemic immune inflammation index and nomogram in predicting the prognosis of patients with mucoepidermoid carcinoma].

PURPOSE: To investigate the relationship between preoperative systemic immune-inflammation index (SII) and relapse-free survival (RFS) after surgical resection of mucoepidermoid carcinoma(MEC). METHODS: The data of 135 patients with MEC who underwent surgical resection in the First Affiliated Hospital of Zhengzhou University from January 2016 to July 2019 were collected, and the receiver operating characteristic(ROC) curve was performed on the SII of patients. The optimal cut-off value was obtained by ROC analysis. Therefore, the patients' SII index was divided into high and low group, and survival analysis was performed by Kaplan-Meier method. Cox proportional regression model and least absolute shrinkage and selection operator (LASSO) were used to analyze the factors influencing prognosis, and a nomogram model was built to predict patients' relapse-free survival(RFS). Area under curve (AUC) and correction curve were used to evaluate the model and verify the consistency. RESULTS: Survival analysis showed that the RFS rate in low SII group was significantly higher than that in high SII group. Cox proportional hazard regression model showed high SII(HR=2.179, 95%CI: 1.072-4.426, P=0.031) and low tumor differentiation(HR=6.894, 95%CI: 2.770-17.158, P=0.000) and cervical lymph node metastasis (HR=2.091, 95%CI: 1.034-4.230, P=0.040) were significant predictors of poor RFS. CONCLUSIONS: The lower the preoperative SII, the better the prognosis of patients. The nomogram prognosis of MEC based on SII is effective.

On-chip integrated metasystem for spin-dependent multi-channel color holography.

On-chip integrated metasurface driven by in-plane guided waves is of great interests in various light-field manipulation applications such as colorful augmented reality and holographic display. However, it remains a challenge to design colorful multichannel holography by a single on-chip metasurface. Here we present metasurfaces integrated on top of a guided-wave photonic slab that achieves multi-channel colorful holographic light display. An end-to-end scheme is used to inverse design the metasurface for projecting off-chip preset multiple patterns. Particular examples are presented for customized patterns that were encoded into the metasurface with a single-cell meta-atom, working simultaneously at RGB color channels and for several different diffractive distances, with polarization dependence. Holographic images are generated at 18 independent channels with such a single-cell metasurface. The proposed design scheme is easy to implement, and the resulting device is viable for fabrication, promising plenty of applications in nanophotonics.

Minor Spliceosomal 65K/RNPC3 Interacts with ANKRD11 and Mediates HDAC3-Regulated Histone Deacetylation and Transcription.

RNA splicing is crucial in the multilayer regulatory networks for gene expression, making functional interactions with DNA- and other RNA-processing machineries in the nucleus. However, these established couplings are all major spliceosome-related; whether the minor spliceosome is involved remains unclear. Here, through affinity purification using Drosophila lysates, an interaction is identified between the minor spliceosomal 65K/RNPC3 and ANKRD11, a cofactor of histone deacetylase 3 (HDAC3). Using a CRISPR/Cas9 system, Deletion strains are constructed and found that both Dm65KΔ/Δ and Dmankrd11Δ/Δ mutants have reduced histone deacetylation at Lys9 of histone H3 (H3K9) and Lys5 of histone H4 (H4K5) in their heads, exhibiting various neural-related defects. The 65K-ANKRD11 interaction is also conserved in human cells, and the HsANKRD11 middle-uncharacterized domain mediates Hs65K association with HDAC3. Cleavage under targets and tagmentation (CUT&Tag) assays revealed that HsANKRD11 is a bridging factor, which facilitates the synergistic common chromatin-binding of HDAC3 and Hs65K. Knockdown (KD) of HsANKRD11 simultaneously decreased their common binding, resulting in reduced deacetylation of nearby H3K9. Ultimately, this study demonstrates that expression changes of many genes caused by HsANKRD11-KD are due to the decreased common chromatin-binding of HDAC3 and Hs65K and subsequently reduced deacetylation of H3K9, illustrating a novel and conserved coupling mechanism that links the histone deacetylation with minor spliceosome for the regulation of gene expression.

Differential impacts of nonsteroidal anti-inflammatory drugs on lifespan and healthspan in aged Caenorhabditis elegans.

Aging and age-related diseases are intricately associated with oxidative stress and inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown their promise in mitigating age-related conditions and potentially extending lifespan in various model organisms. However, the efficacy of NSAIDs in older individuals may be influenced by age-related changes in drug metabolism and tolerance, which could result in age-dependent toxicities. This study aimed to evaluate the potential risks of toxicities associated with commonly used NSAIDs (aspirin, ibuprofen, acetaminophen, and indomethacin) on lifespan, healthspan, and oxidative stress levels in both young and old Caenorhabditis elegans. The results revealed that aspirin and ibuprofen were able to extend lifespan in both young and old worms by suppressing ROS generation and enhancing the expression of antioxidant SOD genes. In contrast, acetaminophen and indomeacin accelerated aging process in old worms, leading to oxidative stress damage and reduced resistance to heat stress through the pmk-1/skn-1 pathway. Notably, the harmful effects of acetaminophen and indomeacin were mitigated when pmk-1 was knocked out in the pmk-1(km25) strain. These results underscore the potential lack of benefit from acetaminophen and indomeacin in elderly individuals due to their increased susceptibility to toxicity. Further research is essential to elucidate the underlying mechanisms driving these age-dependent responses and to evaluate the potential risks associated with NSAID use in the elderly population.

Group A Streptococcal meningitis in children: a short case series and systematic review.

BACKGROUND: Group A streptococcal(GAS) meningitis is a severe disease with a high case fatality rate. In the era of increasing GAS meningitis, our understanding about this disease is limited. PURPOSE: To gain a better understanding about GAS meningitis. METHODS: Five new cases with GAS meningitis were reported. GAS meningitis related literatures were searched for systematic review in PUBMED and EMBASE. Case reports and case series on paediatric cases were included. Information on demographics, risk factors, symptoms, treatments, outcomes, and emm types of GAS was summarized. RESULTS: Totally 263 cases were included. Among 100 individuals, 9.9% (8/81) had prior varicella, 11.1% (9/81) had anatomical factors, and 53.2% (42/79) had extracranial infections. Soft tissue infections were common among infants (10/29, 34.5%), while ear/sinus infections were more prevalent in children ≥ 3 years (21/42, 50.0%). The overall case fatality rate (CFR) was 16.2% (12/74). High risk of death was found in patients with shock or systemic complications, young children(< 3 years) and cases related to hematogenic spread. The predominate cause of death was shock(6/8). Among the 163 patients included in case series studies, ear/sinus infections ranged from 21.4 to 62.5%, while STSS/shock ranged from 12.5 to 35.7%, and the CFR ranged from 5.9 to 42.9%. CONCLUSIONS: A history of varicella, soft tissue infections, parameningeal infections and CSF leaks are important clinical clues to GAS in children with meningitis. Young children and hematogenic spread related cases need to be closely monitored for shock due to the high risk of death.

Pyrazolone compounds could inhibit CES1 and ameliorates fat accumulation during adipocyte differentiation.

Carboxylesterase 1 (CES1), a member of the serine hydrolase superfamily, is involved in a wide range of xenobiotic and endogenous substances metabolic reactions in mammals. The inhibition of CES1 could not only alter the metabolism and disposition of related drugs, but also be benefit for treatment of metabolic disorders, such as obesity and fatty liver disease. In the present study, we aim to develop potential inhibitors of CES1 and reveal the preferred inhibitor structure from a series of synthetic pyrazolones (compounds 1-27). By in vitro high-throughput screening method, we found compounds 25 and 27 had non-competitive inhibition on CES1-mediated N-alkylated d-luciferin methyl ester (NLMe) hydrolysis, while compound 26 competitively inhibited CES1-mediated NLMe hydrolysis. Additionally, Compounds 25, 26 and 27 can inhibit CES1-mediated fluorescent probe hydrolysis in live HepG2 cells with effect. Besides, compounds 25, 26 and 27 could effectively inhibit the accumulation of lipid droplets in mouse adipocytes cells. These data not only provided study basis for the design of newly CES1 inhibitors. The present study not only provided the basis for the development of lead compounds for novel CES1 inhibitors with better performance, but also offered a new direction for the explore of candidate compounds for the treatment of hyperlipidemia and related diseases.

Blocking Sigmar1 exacerbates methamphetamine-induced hypertension.

AIM: Methamphetamine (METH) chronic exposure is an important risk factor for hypertension development. However, the mechanisms behind METH-induced hypertension remain unclear. Therefore, we aimed to reveal the potential mechanisms underlying METH-induced hypertension. METHODS AND RESULTS: We structured the mouse hypertension model by METH, and observed that METH-treated mice have presented vascular remodeling (large-and small-size arteries) with collagen deposit around the vessel and increasing blood pressure (BP) and Sigma1 receptor (Sigmar1) in vascular tissue. We hypothesized that Sigmar1 is crucial in METH-induced hypertension and vascular remodeling. Sigmar1 knockout (KO) mice and antagonist (BD1047) pretreated mice exposed to METH for six-week showed higher BP and more collagen deposited around vessels than wild-type (WT) mice exposed to METH for six-week, in contrast, mice pretreated with Sigmar1 agonist (PRE-084) had unchanged BP and perivascular collagen despite the six-week METH exposure. Furthermore, we found that METH exposure induced vascular smooth muscle cells (VSMCs) and mesenchymal stem cells to differentiate into the myofibroblast-like cell and secrete collagen into surrounding vessels. Mechanically, Sigmar1 can suppress the COL1A1 expression by blocking the classical fibrotic TGF-ß/Smad2/3 signaling pathway in METH-exposed VSMCs and mesenchymal stem cells. CONCLUSION: Our results suggest that Sigmar1 is involved in METH-induced hypertension and vascular fibrosis by blocking the activation of the TGF-ß/Smad2/3 signaling pathway. Accordingly, Sigmar1 may be a novel therapeutic target for METH-induced hypertension and vascular fibrosis.

In Situ Analysis of Interfacial Morphological and Chemical Evolution in All-Solid-State Lithium-Metal Batteries.

Visualizing lithium (Li) ions and understanding Li plating/stripping processes as well as evolution of solid electrolyte interface (SEI) are critical for optimizing all-solid-state Li metal batteries (ASSLMB). However, the buried solid-solid interfaces present a challenge for detection which preclude the employment of multiple analysis techniques. Herein, by employing complementary in situ characterizations, morphological/chemical evolution, Li plating/stripping dynamics and SEI dynamics were efficiently decoupled and Li ion behavior at interface between different solid-state electrolytes (SSE) was successfully detected. The innovative combining experiments of in situ atomic force microscopy and in situ X-ray photoelectron spectroscopy on Li metal anode revealed interfacial morphological/chemical evolution and decoupled Li plating/stripping process from SEI evolution. Though Li plating speed in Li10GeP2S12 (LGPS) was higher than Li3PS4 (LPS), speed of SSE decomposition was similar and ~85% interfacial SSE turned into SEI during plating and remained unchanged in stripping. To leverage strengths of different SSEs, an LPS-LGPS-LPS sandwich electrolyte was developed, demonstrating enhanced ionic conductivity and improved interfacial stability with less SSE decomposition (25%). Using in situ Kelvin Probe Force Microscopy, Li-ion behavior at interface between different SSEs was effectively visualized, uncovering distribution of Li ions at LGPS|LPS interface under different potentials.

A new era of cancer immunotherapy: combining revolutionary technologies for enhanced CAR-M therapy.

Significant advancements have been made in the application of chimeric antigen receptor (CAR)-T treatment for blood cancers during the previous ten years. However, its effectiveness in treating solid tumors is still lacking, necessitating the exploration of alternative immunotherapies that can overcome the significant challenges faced by current CAR-T cells. CAR-based immunotherapy against solid tumors shows promise with the emergence of macrophages, which possess robust phagocytic abilities, antigen-presenting functions, and the ability to modify the tumor microenvironment and stimulate adaptive responses. This paper presents a thorough examination of the latest progress in CAR-M therapy, covering both basic scientific studies and clinical trials. This study examines the primary obstacles hindering the realization of the complete potential of CAR-M therapy, as well as the potential strategies that can be employed to overcome these hurdles. With the emergence of revolutionary technologies like in situ genetic modification, synthetic biology techniques, and biomaterial-supported gene transfer, which provide a wider array of resources for manipulating tumor-associated macrophages, we suggest that combining these advanced methods will result in the creation of a new era of CAR-M therapy that demonstrates improved efficacy, safety, and availability.

Dual-Mechanism Peptide SR25 has Broad Antimicrobial Activity and Potential Application for Healing Bacteria-infected Diabetic Wounds.

The rise of antibiotic resistance poses a significant public health crisis, particularly due to limited antimicrobial options for the treatment of infections with Gram-negative pathogens. Here, an antimicrobial peptide (AMP) SR25 is characterized, which effectively kills both Gram-negative and Gram-positive bacteria through a unique dual-targeting mechanism without detectable resistance. Meanwhile, an SR25-functionalized hydrogel is developed for the efficient treatment of infected diabetic wounds. SR25 is obtained through genome mining from an uncultured bovine enteric actinomycete named Nonomuraea Jilinensis sp. nov. Investigations reveal that SR25 has two independent cellular targets, disrupting bacterial membrane integrity and restraining the activity of succinate:quinone oxidoreductase (SQR). In a diabetic mice wound infection model, the SR25-incorporated hydrogel exhibits high efficacy against mixed infections of Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA), accelerating wound healing. Overall, these findings demonstrate the therapeutic potential of SR25 and highlight the value of mining drugs with multiple mechanisms from uncultured animal commensals for combating challenging bacterial pathogens.

A near-infrared fluorescent probe for imaging peroxynitrite levels in paw edema mice and drug evaluation.

A near-infrared fluorescent probe (TX-P) for detecting peroxynitrite is constructed. The probe has a near-infrared emission (725 nm), large Stokes shift (125 nm) and excellent sensitivity and selectivity. In addition, TX-P can be used to visualize ONOO- in living cells, image ONOO- in paw edema mice and evaluate anti-inflammatory drugs.