LL37-mtDNA regulates viability, apoptosis, inflammation, and autophagy in lipopolysaccharide-treated RLE-6TN cells by targeting Hsp90aa1.

Sepsis-induced acute lung injury is associated with lung epithelial cell injury. This study analyzed the role of the antimicrobial peptide LL37 with mitochondrial DNA (LL37-mtDNA) and its potential mechanism of action in lipopolysaccharide (LPS)-treated rat type II alveolar epithelial cells (RLE-6TN cells). RLE-6TN cells were treated with LPS alone or with LL37-mtDNA, followed by transcriptome sequencing. Differentially expressed and pivotal genes were screened using bioinformatics tools. The effects of LL37-mtDNA on cell viability, inflammation, apoptosis, reactive oxygen species (ROS) production, and autophagy-related hallmark expression were evaluated in LPS-treated RLE-6TN cells. Additionally, the effects of Hsp90aa1 silencing following LL37-mtDNA treatment were investigated in vitro. LL37-mtDNA further suppressed cell viability, augmented apoptosis, promoted the release of inflammatory cytokines, increased ROS production, and elevated LC3B expression in LPS-treated RLE-6TN cells. Using transcriptome sequencing and bioinformatics, ten candidate genes were identified, of which three core genes were verified to be upregulated in the LPS + LL37-mtDNA group. Additionally, Hsp90aa1 downregulation attenuated the effects of LL37-mtDNA on LPS-treated RLE-6TN cells. Hsp90aa1 silencing possibly acted as a crucial target to counteract the effects of LL37-mtDNA on viability, apoptosis, inflammation, and autophagy activation in LPS-treated RLE-6TN cells.

Optimal target mean arterial pressure for patients with sepsis-associated encephalopathy: a retrospective cohort study.

BACKGROUND: Sepsis-associated encephalopathy (SAE) patients often experience changes in intracranial pressure and impaired cerebral autoregulation. Mean arterial pressure (MAP) plays a crucial role in cerebral perfusion pressure, but its relationship with mortality in SAE patients remains unclear. This study aims to investigate the relationship between MAP and the risk of 28-day and in-hospital mortality in SAE patients, providing clinicians with the optimal MAP target. METHODS: We retrospectively collected clinical data of patients diagnosed with SAE on the first day of ICU admission from the MIMIC-IV (v2.2) database. Patients were divided into four groups based on MAP quartiles. Kruskal-Wallis H test and Chi-square test were used to compare clinical characteristics among the groups. Restricted cubic spline and segmented Cox regression models, both unadjusted and adjusted for multiple variables, were employed to elucidate the relationship between MAP and the risk of 28-day and in-hospital mortality in SAE patients and to identify the optimal MAP. Subgroup analyses were conducted to assess the stability of the results. RESULTS: A total of 3,816 SAE patients were included. The Q1 group had higher rates of acute kidney injury and vasoactive drug use on the first day of ICU admission compared to other groups (P < 0.01). The Q1 and Q4 groups had longer ICU and hospital stays (P < 0.01). The 28-day and in-hospital mortality rates were highest in the Q1 group and lowest in the Q3 group. Multivariable adjustment restricted cubic spline curves indicated a nonlinear relationship between MAP and mortality risk (P for nonlinearity < 0.05). The MAP ranges associated with HRs below 1 for 28-day and in-hospital mortality were 74.6-90.2 mmHg and 74.6-89.3 mmHg, respectively.The inflection point for mortality risk, determined by the minimum hazard ratio (HR), was identified at a MAP of 81.5 mmHg. The multivariable adjusted segmented Cox regression models showed that for MAP < 81.5 mmHg, an increase in MAP was associated with a decreased risk of 28-day and in-hospital mortality (P < 0.05). In Model 4, each 5 mmHg increase in MAP was associated with a 15% decrease in 28-day mortality risk (HR: 0.85, 95% CI: 0.79-0.91, p < 0.05) and a 14% decrease in in-hospital mortality risk (HR: 0.86, 95% CI: 0.80-0.93, p < 0.05). However, for MAP ≥ 81.5 mmHg, there was no significant association between MAP and mortality risk (P > 0.05). Subgroup analyses based on age, congestive heart failure, use of vasoactive drugs, and acute kidney injury showed consistent results across different subgroups.Subsequent analysis of SAE patients with septic shock also showed results similar to those of the original cohort.However, for comatose SAE patients (GCS ≤ 8), there was a negative correlation between MAP and the risk of 28-day and in-hospital mortality when MAP was < 81.5 mmHg, but a positive correlation when MAP was ≥ 81.5 mmHg in adjusted models 2 and 4. CONCLUSION: There is a nonlinear relationship between MAP and the risk of 28-day and in-hospital mortality in SAE patients. The optimal MAP target for SAE patients in clinical practice appears to be 81.5 mmHg.

Negative association of serum neurofilament light chain with estimated glomerular filtration rate levels and the impact of gender.

Background: The relationship between kidney function and brain function is complex and poorly understood. This study aims to investigate the association between serum neurofilament light chain (sNfL) and levels of estimated glomerular filtration rate (eGFR), offering new insights into their interactions. Methods: Data from the national health and nutrition examination survey (NHANES) in 2013-2014, linked with national death index records, were used. Participants who met specific criteria were analyzed. Baseline characteristics were stratified by tertiles of sNfL levels and compared using weighted Kruskal-Wallis and chi-square tests. Weighted linear regression models, both unadjusted and adjusted, evaluated the relationship between log sNfL and eGFR. Subgroup and interaction analyses validated the findings. Restricted cubic spline, scatter plots, and Spearman correlation confirmed the relationship between log sNfL and eGFR. Results: A total of 2,038 eligible participants were included. Higher sNfL levels were significantly associated with lower eGFR (p < 0.01). The highest sNfL tertile had a significantly higher mortality rate (p < 0.01). Fully adjusted multivariable weighted linear regression showed a significant negative correlation between log sNfL and eGFR (per 10-unit increase; ß = -0.07, 95% CI: -0.10 to -0.04, p < 0.01). Subgroup analyses consistently supported this negative correlation (p < 0.01). Interaction analysis revealed a significant gender difference (p = 0.032), with males showing a - 0.06 (-0.09, -0.04) decrease and females a - 0.07 (-0.11, -0.04) decrease in log sNfL per 10-unit increase in eGFR. Restricted cubic spline confirmed a linear relationship (p-non-linear = 0.121), and the Spearman correlation coefficient was -0.45. Females had slightly lower log sNfL levels compared to males at equivalent eGFR levels. Conclusion: A significant negative correlation was found between log sNfL and eGFR levels. Gender influenced the degree of this negative association. Further research is needed to validate these findings and elucidate their underlying mechanisms.

UCP2 knockout exacerbates sepsis-induced intestinal injury by promoting NLRP3-mediated pyroptosis.

Sepsis-induced intestinal injury is a common complication that increases the morbidity and mortality associated with sepsis. UCP2, a mitochondrial membrane protein, is involved in numerous cellular processes, including metabolism, inflammation, and pyroptosis. According to our previous studies, UCP2 expression increases in septic intestinal tissue. However, its function in intestinal damage is not known. This work investigated UCP2's role in intestinal injury caused by sepsis. A sepsis mouse model was established in wild-type and UCP2-knockout (UCP2-KO) animals using cecal ligation and puncture (CLP). MCC950, an NLRP3 inflammasome inhibitor, was injected intraperitoneally 3 h before CLP surgery. Overall, significantly higher levels of UCP2 were observed in the intestines of septic mice. UCP2-KO mice subjected to CLP exhibited exacerbated intestinal damage, characterized by enhanced mucosal erosion, inflammatory cell infiltration, and increased intestinal permeability. Furthermore, UCP2 knockout significantly increased oxidative stress, inflammation, and pyroptosis in the CLP mouse intestines. Interestingly, MCC950 not only inhibited pyroptosis but also reversed inflammation, oxidative stress as well as damage to intestinal tissues as a result of UCP2 knockout. Our results highlighted the protective functions of UCP2 in sepsis-associated intestinal injury through modulation of inflammation and oxidative stress via NLRP3 inflammasome-induced pyroptosis.

Surgical timing for asphyxiating thoracic dystrophy.

This report describes a 4-year-old girl diagnosed with asphyxiating thoracic dystrophy who experienced severe respiratory distress and multiple complications after undergoing a corrective operation for a thoracic deformity. The optimal age for children with asphyxiating thoracic dystrophy to receive a corrective operation is between 6 and 12 years old. For children under 6 years old, the decision to undergo an operation should be carefully evaluated.

Colorimetric detection of neomycin sulfate in serum based on ultra-small gold nanoparticles with peroxidase-like activity.

Neomycin sulfate (NEO) is a kind of aminoglycoside antibiotics. Because of its strong ototoxicity, nephrotoxicity and other side effects, its content in the body should be strictly monitored during use. In this paper, a rapid colorimetric detection method for NEO based on ultrasmall polyvinylpyrrolidone modified gold nanoparticles (PVP/Au NPs) with peroxidase-like activity was developed. Firstly, ultra small PVP/Au NPs with weak peroxidase-like activity were synthetized. When they were mixed with NEO, strong hydrogen bonds were formed between NEO and PVP, resulting in the aggregation of PVP/Au NPs, and the aggregated PVP/Au NPs showed stronger peroxidase-like activity. Therefore, rapid colorimetric detection of NEO was achieved by utilizing the enhanced peroxidase-like activity mechanism caused by the aggregation of ultra small PVP/Au NPs. The naked eye detection limit of this method is 50 nM. Within the range of 1 nM-300 nM, there was a good linear relationship between NEO concentration and the change in absorbance intensity of PVP/Au NPs-H2O2-TMB solution at 652 nm, with the regression curve of y = 0.0045x + 0.0525 (R2 = 0.998), and the detection limit is 1 nM. In addition, this method was successfully applied to the detection of NEO in mouse serum. The recoveries were 104.4 % -107.6 % compared with HPLC assay results, indicating that this method for NEO detection based on PVP/Au NPs has great potential in actual detection of NEO in serum.

Sybil Attacks Detection and Traceability Mechanism Based on Beacon Packets in Connected Automobile Vehicles.

Connected Automobile Vehicles (CAVs) enable cooperative driving and traffic management by sharing traffic information between them and other vehicles and infrastructures. However, malicious vehicles create Sybil vehicles by forging multiple identities and sharing false location information with CAVs, misleading their decisions and behaviors. The existing work on defending against Sybil attacks has almost exclusively focused on detecting Sybil vehicles, ignoring the traceability of malicious vehicles. As a result, they cannot fundamentally alleviate Sybil attacks. In this work, we focus on tracking the attack source of malicious vehicles by using a novel detection mechanism that relies on vehicle broadcast beacon packets. Firstly, the roadside units (RSUs) randomly instruct vehicles to perform customized key broadcasting and listening within communication range. This allows the vehicle to prove its physical presence by broadcasting. Then, RSU analyzes the beacon packets listened to by the vehicle and constructs a neighbor graph between the vehicles based on the customized particular fields in the beacon packets. Finally, the vehicle's credibility is determined by calculating the edge success probability of vehicles in the neighbor graph, ultimately achieving the detection of Sybil vehicles and tracing malicious vehicles. The experimental results demonstrate that our scheme achieves the real-time detection and tracking of Sybil vehicles, with precision and recall rates of 98.53% and 95.93%, respectively, solving the challenge of existing detection schemes failing to combat Sybil attacks from the root.

Multifunctional polyaniline modified calcium alginate aerogel membrane with antibacterial, oil-water separation, dye and heavy metal ions removal properties for complex water purification.

With the rapid development of urbanization, the discharge of industrial wastewater has led to increasingly critical water pollution issues. Additionally, heavy metals, organic dyes, microorganisms and oil pollution often coexist and have persistence and harmfulness. Developing materials that can treat these complex pollutants simultaneously has important practical significance. In this study, a calcium alginate-based aerogel membrane (PANI@CA membrane) was prepared by spraying, polymerization, Ca2+ cross-linking and freeze-drying using aniline and sodium alginate as raw materials. Oil-water emulsion can be separated by PANI@CA membrane only under gravity, and the separation efficiency was as high as 99 %. At the same time, the membrane can effectively intercept or adsorb organic dyes and heavy metal ions. The removal rates of methylene blue and Congo red were above 92 % and 63 % respectively even after ten times of cyclic filtration. The removal rate of Pb2+ was up to 95 %. In addition, PANI@CA membrane shows excellent photothermal conversion ability, and it can effectively kill Staphylococcus aureus under 808 nm laser irradiation. PANI@CA membrane has the advantages of low cost, simple preparation, good stability and high recycling ability, and has potential application prospects in wastewater treatment.

Aberrant mitochondrial aggregation of TDP-43 activated mitochondrial unfolded protein response and contributed to recovery of acetaminophen induced acute liver injury.

Mitochondrial dysfunction is a key pathological event in the acute liver injury following the overdose of acetaminophen (APAP). Calpain is the calcium-dependent protease, recent studies demonstrate that it is involved in the impairment of mitochondrial dynamics. The mitochondrial unfolded protein response (UPRmt) is commonly activated in the context of mitochondrial damage following pathological insults and contributes to the maintenance of the mitochondrial quality control through regulating a wide range of gene expression. More importantly, it is reported that abnormal aggregation of TDP-43 in mitochondria induced the activation of UPRmt. However, whether it is involved in APAP induced-hepatotoxicity remains unclear. In the present study, C57/BL6 mice were given 300 mg/kg APAP to establish a time-course model of acute liver injury. Furthermore, Calpeptin, the specific inhibiter of calpains, was used to conduct the intervention experiment. Our results showed, APAP exposure produced severe liver injury. Moreover, TDP-43 was obviously accumulated within mitochondria whereas mitochondrial protease LonP1 was significantly decreased. However, these changes exhibited significant recovery at 48 h. By contrast, the mitochondrial protease ClpP and chaperone mtHSP70 and HSP60 were consistently increased, which supported the UPRmt was activated to promote protein homeostasis. Further investigation revealed that calpain-mediated cleavage of TDP-43 could promote the accumulation of TDP-43 in mitochondria compartment, thereby facilitating the activation of UPRmt. Additionally, Calpeptin pretreatment not only protected against APAP-induced liver injury, but also suppressed the formation of TDP-43 aggregates and the activation of UPRmt. Taken together, our findings indicated that in APAP-induced acute liver injury, calpain-mediated cleavage of TDP43 caused its aberrant aggregation on the mitochondria. As a stress-protective response, the induction of UPRmt contributed to the recovery of mitochondrial function.

Prediction models of surgical site infection after gastrointestinal surgery: a nationwide prospective cohort study.

OBJECTIVE: This study aimed to construct and validate a clinical prediction model for surgical site infection (SSI) risk 30 days after gastrointestinal surgery. MATERIALS AND METHODS: This multicentre study involving 57 units conducted a 30-day postoperative follow-up of 17 353 patients who underwent gastrointestinal surgery at the unit from 1 March 2021 to 28 February 2022. The authors collected a series of hospitalisation data, including demographic data, preoperative preparation, intraoperative procedures and postoperative care. The main outcome variable was SSI, defined according to the Centres for Disease Control and Prevention guidelines. This study used the least absolute shrinkage and selection operator (LASSO) algorithm to screen predictive variables and construct a prediction model. The receiver operating characteristic curve, calibration and clinical decision curves were used to evaluate the prediction performance of the prediction model. RESULTS: Overall, 17 353 patients were included in this study, and the incidence of SSI was 1.6%. The univariate analysis combined with LASSO analysis showed that 20 variables, namely, chronic liver disease, chronic kidney disease, steroid use, smoking history, C-reactive protein, blood urea nitrogen, creatinine, albumin, blood glucose, bowel preparation, surgical antibiotic prophylaxis, appendix surgery, colon surgery, approach, incision type, colostomy/ileostomy at the start of the surgery, colostomy/ileostomy at the end of the surgery, length of incision, surgical duration and blood loss were identified as predictors of SSI occurrence ( P <0.05). The area under the curve values of the model in the train and test groups were 0.7778 and 0.7868, respectively. The calibration curve and Hosmer-Lemeshow test results demonstrated that the model-predicted and actual risks were in good agreement, and the model forecast accuracy was high. CONCLUSIONS: The risk assessment system constructed in this study has good differentiation, calibration and clinical benefits and can be used as a reference tool for predicting SSI risk in patients.

Indolo[3,2-b]indole-based multi-resonance emitters for efficient narrowband pure-green organic light-emitting diodes.

Organic light-emitting diodes (OLEDs) utilizing multi-resonance (MR) emitters show great potential in ultrahigh-definition display benefitting from superior merits of MR emitters such as high color purity and photoluminescence quantum yields. However, the scarcity of narrowband pure-green MR emitters with novel backbones and facile synthesis has limited their further development. Herein, two novel pure-green MR emitters (IDIDBN and tBuIDIDBN) are demonstrated via replacing the carbazole subunits in the bluish-green BCzBN skeleton with new polycyclic aromatic hydrocarbon (PAH) units, 5-phenyl-5,10-dihydroindolo[3,2-b]indole (IDID) and 5-(4-(tert-butyl)phenyl)-5,10-dihydroindolo[3,2-b]indole (tBuIDID), to simultaneously enlarge the π-conjugation and enhance the electron-donating strength. Consequently, a successful red shift from aquamarine to pure-green is realized for IDIDBN and tBuIDIDBN with photoluminescence maxima peaking at 529 and 532 nm, along with Commission Internationale de l'Eclairage (CIE) coordinates of (0.25, 0.71) and (0.28, 0.70). Furthermore, both emitters revealed narrowband emission with small full width at half-maximum (FWHM) below 28 nm. Notably, the narrowband pure-green emission was effectively preserved in corresponding devices, which afford elevated maximum external quantum efficiencies of 16.3% and 18.3% for IDIDBN and tBuIDIDBN.

Real-Time Detection Algorithm for Kiwifruit Canker Based on a Lightweight and Efficient Generative Adversarial Network.

Disease diagnosis and control play important roles in agriculture and crop protection. Traditional methods of identifying plant disease rely primarily on human vision and manual inspection, which are subjective, have low accuracy, and make it difficult to estimate the situation in real time. At present, an intelligent detection technology based on computer vision is becoming an increasingly important tool used to monitor and control crop disease. However, the use of this technology often requires the collection of a substantial amount of specialized data in advance. Due to the seasonality and uncertainty of many crop pathogeneses, as well as some rare diseases or rare species, such data requirements are difficult to meet, leading to difficulties in achieving high levels of detection accuracy. Here, we use kiwifruit trunk bacterial canker (Pseudomonas syringae pv. actinidiae) as an example and propose a high-precision detection method to address the issue mentioned above. We introduce a lightweight and efficient image generative model capable of generating realistic and diverse images of kiwifruit trunk disease and expanding the original dataset. We also utilize the YOLOv8 model to perform disease detection; this model demonstrates real-time detection capability, taking only 0.01 s per image. The specific contributions of this study are as follows: (1) a depth-wise separable convolution is utilized to replace part of ordinary convolutions and introduce noise to improve the diversity of the generated images; (2) we propose the GASLE module by embedding a GAM, adjust the importance of different channels, and reduce the loss of spatial information; (3) we use an AdaMod optimizer to increase the convergence of the network; and (4) we select a real-time YOLOv8 model to perform effect verification. The results of this experiment show that the Fréchet Inception Distance (FID) of the proposed generative model reaches 84.18, having a decrease of 41.23 compared to FastGAN and a decrease of 2.1 compared to ProjectedGAN. The mean Average Precision (mAP@0.5) on the YOLOv8 network reaches 87.17%, which is nearly 17% higher than that of the original algorithm. These results substantiate the effectiveness of our generative model, providing a robust strategy for image generation and disease detection in plant kingdoms.

Chronic carbon disulfide exposure induces parkinsonian pathology via α-synuclein aggregation and necrosome complex interaction.

Exposure to carbon disulfide (CS2) has been associated with an increased incidence of parkinsonism in workers, but the mechanism underlying this association remains unclear. Using a rat model, we investigated the effects of chronic CS2 exposure on parkinsonian pathology. Our results showed that CS2 exposure leads to significant motor impairment and neuronal damage, including loss of dopaminergic neurons and degeneration of the substantia nigra pars compacta (SNpc). The immunoassays revealed that exposure to CS2 induces aggregation of α-synuclein and phosphorylated α-synuclein, as well as activation of necroptosis in the SNpc. Furthermore, in vitro and in vivo experiments demonstrated that the interaction between α-synuclein and the necrosome complex (RIP1, RIP3, and MLKL) is responsible for the loss of neuronal cells after CS2 exposure. Taken together, our results demonstrate that CS2-mediated α-synuclein aggregation can induce dopaminergic neuron damage and parkinsonian behavior through interaction with the necrosome complex.

RIPK3-MLKL necroptotic signalling amplifies STING pathway and exacerbates lethal sepsis.

BACKGROUNDS: The stimulator of interferon genes (STING) is an important driver in various inflammatory diseases. METHODS AND RESULTS: Here, we have demonstrated that inhibition of RIPK3 and MLKL dampens STING signaling, indicating that necroptosis may be involved in sustaining STING signaling. Furthermore, RIPK3 knockout in HT-29 cells significantly suppressed STING signaling. Mechanistically, RIPK3 inhibits autophagic flux during STING activation. RIPK3 knockout inhibits STING signaling by intensifying STING autophagy. In contrast, MLKL regulates the STING pathway bidirectionally. MLKL deficiency enhances STING signaling, whereas suppression of MLKL-mediated pore formation restricts STING signaling. Mechanistically, upon abrogating the pro-necroptotic activity of MLKL, MLKL bound to activated STING is secreted to the extracellular space, where it restricts TBK1 and IRF3 recruitment. Targeting necroptotic signaling ameliorates STING activation during DMXAA-induced intestinal injury and sepsis. CONCLUSIONS: These findings elucidate molecular mechanisms linking necroptosis to the STING pathway, and suggest a potential benefit of therapeutic targeting of necroptosis in STING-driven inflammatory diseases.

EXOSOMAL CIRCVMA21 DERIVED FROM ADIPOSE-DERIVED STEM CELLS ALLEVIATES SEPSIS-INDUCED ACUTE KIDNEY INJURY BY TARGETING MIR-16-5P.

ABSTRACT: Background: Exosome from adipose-derived stem cells (ADSCs-Exo) has been shown to inhibit the progression of human diseases, including sepsis-related acute kidney injury (AKI). CircVMA21 is considered to be an important regulator for sepsis-related AKI. However, whether ADSCs-Exo affected sepsis-induced AKI by delivering circVMA21 is not clear. Methods: Adipose-derived stem cells were identified by alizarin red staining, oil red O staining, and flow cytometry. Exosome from adipose-derived stem cells was authenticated by transmission electron microscopy, nanoparticle tracking analysis, western blot analysis, and immunofluorescence assay. Cell apoptosis was assessed by flow cytometry, and inflammation cytokine levels were determined by ELISA. Lactate production was assessed using Lactate Acid Content Assay Kit. The expression levels of aerobic glycolysis-related markers, circVMA21 and miR-16-5p, was evaluated by quantitative real time-polymerase chain reaction. Dual-luciferase reporter assay and RIP assay were employed to detect RNA interaction. Animal experiments were used to evaluate the role of ADSCs-Exo on renal function and cell injury in LPS-induced AKI mice model. Results: Exosome from adipose-derived stem cells inhibited LPS-induced HK-2 cell apoptosis, inflammation, and aerobic glycolysis. Knockdown of exosomal circVMA21 derived from ADSCs enhanced HK-2 cell injury induced by LPS. In terms of mechanism, circVMA21 could serve as sponge for miR-16-5p. Besides, miR-16-5p inhibitor reversed the promotion effect of Exo-sh-circVMA21 on LPS-induced cell injury. In addition, ADSCs-Exo protected LPS-induced AKI in mice by increasing circVMA21 expression and decreasing miR-16-5p expression. Conclusion: Exosomal circVMA21 derived by ADSCs relieved LPS-induced AKI through targeting miR-16-5p, which provided a potential molecular target for treating sepsis-related AKI.

Identification of Risk Factors and Phenotypes of Surgical Site Infection in Patients After Abdominal Surgery.

OBJECTIVES: We aimed to determine the current incidence rate and risk factors for surgical site infection (SSI) after abdominal surgery in China and to further demonstrate the clinical features of patients with SSI. BACKGROUND: Contemporary epidemiology and clinical features of SSI after abdominal surgery remain poorly characterized. METHODS: A prospective multicenter cohort study was conducted from March 2021 to February 2022; the study included patients who underwent abdominal surgery at 42 hospitals in China. Multivariable logistic regression analysis was performed to identify risk factors for SSI. Latent class analysis (LCA) was used to explore the population characteristics of SSI. RESULTS: In total, 23,982 patients were included in the study, of whom 1.8% developed SSI. There was a higher SSI incidence in open surgery (5.0%) than in laparoscopic or robotic surgeries (0.9%). Multivariable logistic regression indicated that the independent risk factors for SSI after abdominal surgery were older age, chronic liver disease, mechanical bowel preparation, oral antibiotic bowel preparation, colon or pancreas surgery, contaminated or dirty wounds, open surgery, and colostomy/ileostomy. LCA revealed 4 subphenotypes in patients undergoing abdominal surgery. Types α and ß were mild subclasses with a lower SSI incidence; whereas types γ and δ were the critical subgroups with a higher SSI incidence, but their clinical features were different. CONCLUSIONS: LCA identified 4 subphenotypes in patients who underwent abdominal surgery. Types γ and δ were critical subgroups with a higher SSI incidence. This phenotype classification can be used to predict SSI after abdominal surgery.

Mitophagy suppresses motor neuron necroptotic mitochondrial damage and alleviates necroptosis that converges to SARM1 in acrylamide-induced dying-back neuropathy.

Acrylamide (ACR), a common industrial ingredient that is also found in many foodstuffs, induces dying-back neuropathy in humans and animals. However, the mechanisms remain poorly understood. Sterile alpha and toll/interleukin 1 receptor motif-containing protein 1 (SARM1) is the central determinant of axonal degeneration and has crosstalk with different cell death programs to determine neuronal survival. Herein, we illustrated the role of SARM1 in ACR-induced dying-back neuropathy. We further demonstrated the upstream programmed cell death mechanism of this SARM1-dependent process. Spinal cord motor neurons that were induced to overexpress SARM1 underwent necroptosis rather than apoptosis in ACR neuropathy. Mechanically, non-canonical necroptotic pathways mediated mitochondrial permeability transition pore (mPTP) opening, reactive oxygen species (ROS) production, and mitochondrial fission. What's more, the final executioner of necroptosis, phosphorylation-activated mixed lineage kinase domain-like protein (MLKL), aggregated in mitochondrial fractions. Rapamycin intervention removed the impaired mitochondria, inhibited necroptosis for axon maintenance and neuronal survival, and alleviated ACR neuropathy. Our work clarified the functional links among mitophagy, necroptosis, and SARM1-dependent axonal destruction during ACR intoxication, providing novel therapeutic targets for dying-back neuropathies.

Increased IP3R-3 degradation induced by acrylamide promoted Ca2+-dependent calpain activation and axon damage in rats.

Occupational and environmental exposure to acrylamide (ACR) can cause selective peripheral and central nerve fiber degeneration. IP3R-3 is an important transmembrane Ca2+ channel on the endoplasmic reticulum (ER), previous studies have found that ACR could induce Ca2+-dependent calpain activation and axon injury, but the exact role of IP3R-3 in ACR neuropathy is still unclear. Here we show that ACR exposure (40 mg/kg) markedly increased the ubiquitination of IP3R-3 in rat spinal cords, and promoted the degradation of IP3R-3 through the ubiquitin-proteasome pathway. Furthermore, the normal structure of ER, especially the mitochondrial associated membranes (MAMs) component, was significantly impaired in ACR neuropathy, and the ER stress pathway was activated, which indicated that the aberrant increase of cytoplasmic Ca2+ could be attributed the destruction of IP3R-3. Further investigation demonstrated that the proteasome inhibitor MG-132 effectively rescued the IP3R-3 loss, attenuated the intracellular Ca2+ increase, and reduced the axon loss of Neuron 2a (N2a) cells following ACR exposure. Moreover, the calpain inhibitor ALLN also reduced the loss of IP3R-3 and axon injury in N2a cells, but did not alleviate the Ca2+ increase in cytosol, supporting that the abnormal ubiquitination of IP3R-3 was the upstream of the cellular Ca2+ rise and axon damage in ACR neuropathy. Taken together, our results suggested that the aberrant IP3R-3 degradation played an important role in the disturbance of Ca2+ homeostasis and the downstream axon loss in ACR neuropathy, thus providing a potential therapeutic target for ACR neurotoxicity.

Potential distribution of Leptotrombidium scutellare in Yunnan and Sichuan Provinces, China, and its association with mite-borne disease transmission.

BACKGROUND: Leptotrombidium scutellare is one of the six main vectors of scrub typhus in China and is a putative vector of hemorrhagic fever with renal syndrome (HFRS). This mite constitutes a large portion of the chigger mite community in southwest China. Although empirical data on its distribution are available for several investigated sites, knowledge of the species' association with human well-being and involvement in the prevalence of mite-borne diseases remains scarce. METHODS: Occurrence data on the chigger mite were obtained from 21 years (2001-2021) of field sampling. Using boosted regression tree (BRT) ecological models based on climate, land cover and elevation variables, we predicted the environmental suitability for L. scutellare in Yunnan and Sichuan Provinces. The potential distribution range and shifts in the study area for near-current and future scenarios were mapped and the scale of L. scutellare interacting with human activities was evaluated. We tested the explanatory power of the occurrence probability of L. scutellare on incidences of mite-borne diseases. RESULTS: Elevation and climate factors were the most important factors contributing to the prediction of the occurrence pattern of L. scutellare. The most suitable habitats for this mite species were mainly concentrated around high-elevation areas, with predictions for the future showing a trend towards a reduction. Human activity was negatively correlated with the environmental suitability of L. scutellare. The occurrence probability of L. scutellare in Yunnan Province had a strong explanatory power on the epidemic pattern of HFRS but not scrub typhus. CONCLUSIONS: Our results emphasize the exposure risks introduced by L. scutellare in the high-elevation areas of southwest China. Climate change may lead to a range contraction of this species towards areas of higher elevation and lessen the associated exposure risk. A comprehensive understanding of the transmission risk requires more surveillance efforts.