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AbstractThis study evaluates the effects of dietary Chinese herb ultrafine powder (CHUP) supplementation in late-phase laying hens on the quality and nutritional values of eggs. A total of 576 Xinyang black-feather laying hens (300-day-old) were randomly allocated into eight groups for a 120-day feeding trial. Each group contained eight replicates with nine hens per replicate. The experimental groups included the control (basal diet) and different levels of CHUP groups (details in ‘Materials and methods’). The results showed that the eggshell strength was increased (p

AbstractChinese herbal formula (CHF) has the potential to improve the performance of aged laying hens through integrated regulation of various physiological functions. The present study aimed to investigate the effects of dietary CHF supplementation on the yolk fatty acid profile in aged laying hens. A total of 144 healthy 307-day-old Xinyang black-feather laying hens were randomly allocated into two groups: a control group (CON, fed a basal diet) and a CHF group (fed a basal diet supplemented with 1% CHF; contained 0.30% Leonurus japonicus Houtt., 0.20% Salvia miltiorrhiza Bge., 0.25% Ligustrum lucidum Ait., and 0.25% Taraxacum mongolicum Hand.-Mazz. for 120 days). The fatty acid concentrations in egg yolks were analyzed using a targeted metabolomics technology at days 60 and 120 of the trial. The results showed that dietary CHF supplementation increased (p

In early February 2024, severe low-temperature rainfall/snowfall and freezing weather events occurred in the eastern parts of Guizhou and the middle and lower reaches of the Yangtze River. Coinciding with the travel period of the Spring Festival, the event caused serious impacts on travel, energy supply guarantees, and people's daily lives. To reveal the exceptional characteristics of the weather event, observation data from the National Meteorological Information Center, NCEP/NCAR reanalysis data, and Huaihua dual-polarization radar data were used to analyze the characteristics and causes of rainfall/snowfall and freezing weather events. The results are as follows: (1) Severe freezing disasters lasting 4-6 days occurred in eastern Guizhou, northern and central parts of Hunan, eastern and southern parts of Hubei, and northern and western parts of Anhui. These disasters were primarily caused by two rounds of low-temperature rain and snow weather. The first round occurred around February 1 to 4, with the most severe period appearing on the 3rd. It was characterized by heavy snowfall and freezing rain, leading to rapid accumulation of snow and ice. The second round occurred from February 5 to 6, with freezing rain predominating in eastern Guizhou and northern and central parts of Hunan, and sleet predominating along the Yangtze River in Hubei and other areas, which sustained or further increased the ice accumulation. (2) The geopotential height anomaly of the mid to high latitudes in Asia showed a distribution of low in the west and high in the east, and the southern trough was active. Both provided important weather conditions for the low-temperature rain and snow weather. The strong southwest jet stream climbs along the front to form a tilted upward airflow, enhancing the precipitation intensity behind the front, and leading to the first round of the weather event. The weakening of the southern trough and the maintenance of the southern front area, the mid-to-low low-level jet, and the surface stationary front resulted in the second round of the weather event. (3) Affected by the formation and maintenance of the South China stationary front and the Yunnan-Guizhou stationary front, the range of inversion was wide, with a significant warm layer in the southern region of the Yangtze River, resulting in different phases of precipitation on the south and north sides of the Yangtze River. Meanwhile, there were significant differences in the vertical direction of the temperature and humidity fields on the north and south sides of the Yangtze River. When heavy snowfall dominated north of the Yangtze River, the temperature and humidity fields exhibited deep cold-wet characteristics, with a typical ice-phrase structure. However, when heavy freezing rain dominated south of the Yangtze River, the temperature and humidity fields exhibited a"strong warm-wet and cold-wet"feature. (4) The rapidly increasing amount of rainwater, ice, and snow formed strong wet snow and severe freezing rain on February 3-4. The low-level supercooled water of both light and heavy rain droplets coexisted in the southern region of the Yangtze River on the night of the 3rd day, while it was dominated by light rain on the night of the 5th day.

Abstract Background Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN). Activation of the neuroinflammatory response has a pivotal role in PD. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for various nerve injuries, but there are limited reports on their use in PD and the underlying mechanisms remain unclear. Methods We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa (hOM)-MSCs on neural functional recovery in both PD models and patients, as well as the preventive effects on mouse models of PD. To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure, we employed single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) combined with full-length transcriptome isoform-sequencing (ISO-seq), and functional assay. Furthermore, we present the findings from an initial cohort of patients enrolled in a phase I first-in-human clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients. Results A functional assay identified that transforming growth factor-β1 (TGF-β1), secreted from hOM-MSCs, played a critical role in modulating mitochondrial function recovery in dopaminergic neurons. This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN, which are closely associated with neuroinflammatory responses. Mechanistically, exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-β1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B (ALK/PI3K/Akt) signaling pathway in microglia located in the SN of PD patients. Furthermore, intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD. Conclusions These findings provide compelling evidence for the involvement of TGF-β1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD. Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD. Additionally, TGF-β1 may be used alone or combined with hOM-MSCs therapy for treating PD.

This study evaluates the utilization of ethyl lactate as an environmentally friendly solvent for extracting phenolic compounds from the Orthosiphon stamineus (O. stamineus) by employing aqueous two-phase system (ATPS). Ethyl lactate (EL) was selected as the primary component for the top phase due to its non-toxic attributes and cost-effectiveness. The impact of type of salt, phase compositions, sample loading, pH, equilibration time, and neutral salt’s composition on the partition coefficient, K; yield, Y; and 2,2-diphenyl-1-pircrylhydrazyl (DPPH) scavenging activity of phenolic compounds was evaluated. The EL-salt ATPS contained 41.9% (w/w) EL and 14.6% (w/w) sulfate at 1.4% (w/w) of sample load, 1.5% (w/w) of potassium chloride, and pH 6.0, had the greatest K of 23.28 ± 0.12, Y of 99.03% ± 1.37%, and DPPH scavenging activity of 98.22% ± 0.40%. Therefore, the study underscores the efficiency of EL-based ATPS for extracting phenolic compounds from plants.

BackgroundShuanghuanglian is a Chinese medicine composed of Honeysuckle Flower, Baical Skullcap Root, and Fructus Forsythiae. It has various effects, including anti-inflammatory, antibacterial, antiviral, and immunomodulatory effects. The fermented product of Shuanghuanglian can be used as an antibiotic alternative, as it has similar efficacy, which may improve the immunity, feed intake and utilization efficiency of laying hens, thus improving their production performance. The aim of this study was to optimize the fermentation conditions for Shuanghuanglian using single factor and response surface methodology, evaluate the chemical and microbial composition of the Shuanghuanglian fermentation liquor (SFL), and explore the effects of SFL on the production performance of laying hens.MethodsA total of 288 Xinyang black-feather laying hens (50 week-old) were randomly allocated to four treatments with nine replicates, each replicate containing eight hens, for a total of 37 days trial (including a 7-day adaptation period). The treatments included a control group (0% SFL in drinking water) and drinking water supplemented with 0.3, 0.5, or 0.7% SFL.ResultsThe fermentation optimization conditions for Shuanghuanglian were selected as a solid-to-liquid ratio at 1:7, 3% inoculation quantity, fermentation temperature at 28°C for 5 days, initial pH of 7, 60 mesh (sieved), and rotation speed of 150 r/min. Various bioactive compounds, such as myrtenol, 2-hexyn-1-ol, arsenous acid tris(trimethylsilyl) ester, 3(10)-caren-4-ol, and oxime-, methoxy-phenyl, were detected in SFL. The most abundant bacterial phyla in SFL were Proteobacteria and Firmicutes, with Acinetobacter being the most abundant genus. The most abundant fungal phyla were Phragmoplastophyta and Magnoliophyta. The 0.5 and 0.7% SFL supplementation in water increased egg weight and laying rate, while decreasing the feed-to-egg ratio of laying hens compared with the control group (p 0.05) in albumen height, egg shape index, egg thickness, and yolk color of the eggs.ConclusionSupplementation of SFL under optimized conditions had a positive impact on the production performance of laying hens, especially when the supplementation amount reached 0.5%. This study provides a theoretical basis for the application of Shuanghuanglian in the commercial egg industry.

Abstract Cancer cells re-program normal lung endothelial cells (EC) into tumor-associated endothelial cells (TEC) that form leaky vessels supporting carcinogenesis. Transcriptional regulators that control the reprogramming of EC into TEC are poorly understood. We identified Forkhead box F1 (FOXF1) as a critical regulator of EC-to-TEC transition. FOXF1 was highly expressed in normal lung vasculature but was decreased in TEC within non-small cell lung cancers (NSCLC). Low FOXF1 correlated with poor overall survival of NSCLC patients. In mice, endothelial-specific deletion of FOXF1 decreased pericyte coverage, increased vessel permeability and hypoxia, and promoted lung tumor growth and metastasis. Endothelial-specific overexpression of FOXF1 normalized tumor vessels and inhibited the progression of lung cancer. FOXF1 deficiency decreased Wnt/β-catenin signaling in TECs through direct transcriptional activation of Fzd4. Restoring FZD4 expression in FOXF1-deficient TECs through endothelial-specific nanoparticle delivery of Fzd4 cDNA rescued Wnt/β-catenin signaling in TECs, normalized tumor vessels and inhibited the progression of lung cancer. Altogether, FOXF1 increases tumor vessel stability, and inhibits lung cancer progression by stimulating FZD4/Wnt/β-catenin signaling in TECs. Nanoparticle delivery of FZD4 cDNA has promise for future therapies in NSCLC.

Abstract Background Desmoplastic fibroma is an extremely rare primary bone tumor. Its characteristic features include bone destruction accompanied by the formation of soft tissue masses. This condition predominantly affects individuals under the age of 30. Since its histology is similar to desmoid-type fibromatosis, an accurate diagnosis before operation is difficult. Desmoplastic fibroma is resistant to chemotherapy, and the efficacy of radiotherapy is uncertain. Surgical excision is preferred for treatment, but it entails high recurrence. Further, skeletal reconstruction post-surgery is challenging, especially in pediatric cases. Case presentation Nine years ago, a 14-year-old male patient presented with a 4-year history of progressive pain in his left wrist. Initially diagnosed as fibrous dysplasia by needle biopsy, the patient underwent tumor resection followed by free vascularized fibular proximal epiphyseal transfer for wrist reconstruction. However, a histological examination confirmed a diagnosis of desmoplastic fibroma. The patient achieved bone union and experienced a recurrence in the ipsilateral ulna 5 years later, accompanied by a wrist deformity. He underwent a second tumor resection and wrist arthrodesis in a single stage. The most recent annual follow-up was in September 2023; the patient had no recurrence and was satisfied with the surgery. Conclusions Desmoplastic fibroma is difficult to diagnose and treat, and reconstruction surgery after tumor resection is challenging. Close follow-up by experienced surgeons may be beneficial for prognosis.

Background: Pulmonary fibrosis is a progressive diffuse parenchymal lung disorder with a high mortality rate. Studies have indicated that injured lung tissues release various pro-inflammatory factors, and produce a large amount of nitric oxide. There is also accumulation of collagen and oxidative stress-induced injury, collectively leading to pulmonary fibrosis. Antrodia cinnamomea is an endemic fungal growth in Taiwan, and its fermented extracts exert anti-inflammatory effects to alleviate liver damages. Hence, we hypothesized and tested the feasibility of using A. cinnamomea extracts for treatment of pulmonary fibrosis. Methods: The TGF-β1-induced human lung fibroblast cells (MRC-5) in vitro cell assay were used to evaluate the effects of A. cinnamomea extracts on the collagen production in MRC-5. Eight-week-old ICR mice were intratracheally administered bleomycin and then fed with an A. cinnamomea extract on day 3 post-administration of bleomycin. At day 21 post-bleomycin administration, the pulmonary functional test, the expression level of inflammation- and fibrosis-related genes in the lung tissue, and the histopathological change were examined. Results: The A. cinnamomea extract significantly attenuated the expression level of collagen in the TGF-β1-induced MRC-5 cells. In the A. cinnamome-treated bleomycin-induced lung fibrotic mice, the bodyweight increased, pulmonary functions improved, the lung tissues expression level of inflammatory factor and the fibrotic indicator were decreased, and the histopathological results showed the reduction of thickening of the inter-alveolar septa. Conclusions: The Antrodia cinnamomea extract significant protects mice against bleomycin-induced lung injuries through improvement of body weight gain and lung functions, and attenuation of expression of inflammatory and fibrotic indicators.

ABSTRACT: The present study aimed to investigate the effects of dietary fermented blueberry pomace (FBP) supplementation on production performance, egg quality and nutritional value, plasma biochemical parameters, follicle number, reproductive hormones, lipid metabolism, and antioxidant capacity of laying hens during the late laying period. A total of 320 (345-d-old) Yukou Jingfen No. 8 laying hens were randomly divided into 4 groups, with eight replicates per group and 10 hens per replicate. The birds were fed a basal diet (control group) and a basal diet supplemented with 0.25, 0.5, and 1.0% FBP. The trial lasted 56 d. The results showed that FBP (0.25−1.0%) supplementation increased the egg albumen height and Haugh unit compared with the control group on d 14, while 0.5 to 1.0% FBP increased the eggshell thickness compared with the 0.25% FBP group on d 28 of the trial (P < 0.05). The methionine content in egg white was higher (P < 0.05) in the 1.0% FBP group compared with the 0.25% FBP group. The CAT activity in the ovary was increased (P < 0.05) in the FBP groups compared with the control group, while plasma GSH-PX activity was higher (P < 0.05) in the 1.0% FBP group compared with the 0.25% FBP and 0.5% FBP groups. Dietary FBP supplementation up-regulated (P < 0.05) gene expressions related to lipid metabolism in the liver (ACC, FAS, SCD1, and SREBP1) and yolk precursor synthesis (ESR2 and VTG II). Moreover, CYP11A1 expression in the ovary was up-regulated (P < 0.05) in the FBP groups compared with the control group, as well as in the 0.25% FBP group compared with the 1.0% FBP group. In summary, dietary FBP supplementation improved egg quality and nutritional value, ovarian antioxidant capacity, and yolk precursor synthesis, while 1.0% FBP had better effects than 0.25 and 0.5% doses.

Background Chronic kidney disease (CKD), which has become a global public health issue, is associated with mitochondrial dysfunction. Niacin is a necessary coenzyme for mitochondrial energy metabolism. However, the association between dietary niacin intake and CKD remains uncertain. This study aimed to investigate the association between dietary niacin intake and CKD in American adults.Methods This is a cross-sectional study. 25,608 individuals aged ≥20 years from the National Health and Nutrition Examination Survey from 2007 to 2018 were involved.Dietary niacin intake was estimated based on 24-hour dietary recalls conducted by trained personnel. CKD was determined by an estimated glomerular filtration rate (eGFR) (

Abstract A nanostructured copper oxide (nCO) coating which can be electrochemically reduced to copper metal is demonstrated as an anti‐reflection coating, enabling interference lithography of three‐dimensionally structured templates on a surface compatible with subsequent electrodeposition steps. The nCO presents a black needle‐like structure which effectively absorbs the incident radiation during interference lithography. Specular and diffused reflectivity measurements confirm nCO has near‐zero reflectivity from at least UV (350 nm) to near IR (700 nm) wavelengths. A particularly important aspect of the nCO is its ability to be reduced to copper metal, enabling electrodeposition inside porous templates fabricated on the nCO. It is demonstrated electrodeposition of copper within 3D templates defined by interference lithography and proximity field nano‐patterning processes, forming mesostructured metals which enhance two‐phase cooling. The resultant 5 µm thick structures exhibited up to 3 times the critical heat flux and 2 times heat transfer coefficient of bare silicon. The structures are optimized via computational tools including Finite Difference Time Domain (FDTD) and COMSOL Multiphysics. The use of the approach demonstrated here can potentially find application in many areas given the broad importance of mesostructured metals for energy, biomedical, and mechanical applications.

Pyrazines are important flavor components and healthy active components in Baijiu, which including tetramethylpyrazine (TTMP). During the brewing process, the traceability of microbial communities and the content distribution characteristics of TTMP are important for improving the quality and style characteristics of compound-flavored Baijiu (CFB). However, the traceability analysis of microorganisms in fermented grains (FG)—used in the production of CFB—lacks quantitative and systematic evaluation. In this study, the microbial communities and TTMP content of Jiuqu (JQ), Liangpei (LP), FG, and pit mud (CP) used in CFB production were characterized; further, coordinate and discriminant analyses were employed to determine differences in microbial communities. Additionally, traceability and correlation analyses were performed to reveal the origin of microbial communities in FG. The source, content, and distribution characteristics of TTMP based on the brewing process have also been discussed. The results showed that most of the bacterial and fungal communities at different levels of FG came from other sources, and the microorganisms of Cladosporium, Acetobacter, Aspergillus, Methanosarcina, and Bacillus were considered have a osculating correlations with TTMP content of FG. Taken together, this study provides insights into the origin of microbial communities in FG and the distribution characteristics of TTMP based on the CFB brewing process. The current findings are conducive for optimizing the fermentation process and improving the quality and style characteristics of CFB.

Fruit and vegetable wastes are linked to the depletion of natural resources and can pose serious health and environmental risks (e.g. eutrophication, water and soil pollution, and GHG emissions) if improperly managed. Current waste management practices often fail to recover high-value compounds from fruit wastes. Among emerging valorization methods, the utilization of fruit wastes as a feedstock for microalgal biorefineries is a promising approach for achieving net zero waste and sustainable development goals. This is due to the ability of microalgae to efficiently sequester carbon dioxide through photosynthesis, utilize nutrients in wastewater, grow in facilities located on non-arable land, and produce several commercially valuable compounds with applications in food, biofuels, bioplastics, cosmetics, nutraceuticals, pharmaceutics, and various other industries. However, the application of microalgal biotechnology towards upcycling fruit wastes has yet to be implemented on the industrial scale due to several economic, technical, operational, and regulatory challenges. Here, we identify sources of fruit waste along the food supply chain, evaluate current and emerging fruit waste management practices, describe value-added compounds in fruit wastes, and review current methods of microalgal cultivation using fruit wastes as a fermentation medium. We also propose some novel strategies for the practical implementation of industrial microalgal biorefineries for upcycling fruit waste in the future.

IntroductionThere is a decline in the quality and nutritive value of eggs in aged laying hens. Fruit pomaces with high nutritional and functional values have gained interest in poultry production to improve the performance.MethodsThe performance, egg nutritive value, lipid metabolism, ovarian health, and cecal microbiota abundance were evaluated in aged laying hens (320 laying hens, 345-day-old) fed on a basal diet (control), and a basal diet inclusion of 0.25%, 0.5%, or 1.0% fermented Aronia melanocarpa pomace (FAMP) for eight weeks.ResultsThe results show that 0.5% FAMP reduced the saturated fatty acids (such as C16:0) and improved the healthy lipid indices in egg yolks by decreasing the atherogenicity index, thrombogenic index, and hypocholesterolemia/hypercholesterolemia ratio and increasing health promotion index and desirable fatty acids (P < 0.05). Additionally, FAMP supplementation (0.25%−1.0%) increased (P < 0.05) the ovarian follicle-stimulating hormone, luteinizing hormone, and estrogen 2 levels, while 1.0% FAMP upregulated the HSD3B1 expression. The expression of VTG II and ApoVLDL II in the 0.25% and 0.5% FAMP groups, APOB in the 0.5% FAMP group, and ESR2 in the 1% FAMP group were upregulated (P < 0.05) in the liver. The ovarian total antioxidant capacity was increased (P < 0.05) by supplementation with 0.25%−1.0% FAMP. Dietary 0.5% and 1.0% FAMP downregulated (P < 0.05) the Keap1 expression, while 1.0% FAMP upregulated (P < 0.05) the Nrf2 expression in the ovary. Furthermore, 1.0% FAMP increased cecal acetate, butyrate, and valerate concentrations and Firmicutes while decreasing Proteobacteria (P < 0.05).ConclusionOverall, FAMP improved the nutritive value of eggs in aged laying hens by improving the liver–blood–ovary function and cecal microbial and metabolite composition, which might help to enhance economic benefits.

Background and purpose: Exogenous bone morphogenetic protein 9 (BMP9) inhibits the malignant progression of human breast cancer, but its expression is often abnormally low in breast cancer. In this study, we intended to explore the expression and role of epigenetically-modified histone lysine-specific demethylase 4A (KDM4A) in breast cancer, and to investigate the relationship between KDM4A and BMP9 and its possible regulatory mechanism. Methods: The expression of KDM4A in breast cancer and its relationship with BMP9 were analyzed by bioinformatics and verified by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blot. Chromatin immunoprecipitation (ChIP) verified the regulatory role of KDM4A on BMP9, and RNA stability experiments and CHX protein stability experiments verified the effect of KDM4A in BMP9 expression. Exogenous recombinant MDA-MB-231 cells transfected with KDM4A small interfering RNA (siKDM4A) or infected with siBMP9 adenovirus (Ad-siBMP9) were constructed using RNA interference technology and adenoviruses knocking down BMP9, and the migratory and invasive abilities of the cells were detected by scratch healing assay and transwell assay, respectively. Results: Bioinformatics analysis showed that the expression of KDM4A was significantly higher in breast cancer than in normal tissues, and there was a negative correlation between the expression of KDM4A and that of BMP9 in breast cancer; RTFQ-PCR and Western blot showed that KDM4A was highly expressed in different breast cancer cell lines, and the knockdown of KDM4A significantly up-regulated BMP9. ChIP experiment confirmed that KDM4A could be significantly enriched in the promoter region of BMP9 gene, reducing its histone lysine 36 position instead of position 4 methyl status, thus silencing the expression of BMP9. RNA stability assay and CHX protein stability assay confirmed that KDM4A had no significant effect on the mRNA of BMP9, but could affect its protein degradation. After knocking down KDM4A, the migration and invasion abilities of breast cancer cells MDA-MB-231 were significantly inhibited, and this effect could be partially reversed by knocking down BMP9. Conclusion: KDM4A is highly expressed in breast cancer and breast cancer cell MDA-MB-231, and can silence its expression by down-regulating the level of histone methylation in the promoter region of the BMP9 gene, as well as affecting the stability of BMP9 at the protein level rather than at the level of mRNA, and promoting the migration and invasion of breast cancer.

Abstract Background The development of alcohol-associated liver disease (ALD) is influenced by the amount and duration of alcohol consumption. The resulting liver damage can range from reversible stages, such as steatosis, steatohepatitis and alcoholic fibrosis, to the advanced and irreversible stage of cirrhosis. Aldo-keto reductase family 1 member A1 (AKR1A1) is a member of the aldo-keto reductase family that catalyzes the reduction of aldehyde groups to their corresponding alcohols in an NADPH-dependent manner. AKR1A1 was found to be downregulated in patients diagnosed with ALD. This study aims to interpret the protective effects of AKR1A1 on the development of ALD. Methods A 5% alcohol-fed (AF) Akr1a1 knockout (Akr1a1 −/−) mouse model and an AML12 hepatocyte model were used. The effects of AKR1A1 on liver function, inflammation, oxidative stress, lipid accumulation, and fibrosis were assessed by ELISA, western blotting, RT‒PCR, and a variety of histological staining methods in AF-induced wild-type (WT) and Akr1a1 −/− mice compared to control liquid diet-fed (PF) WT and Akr1a1 −/− mice. Results The results demonstrated that AF-WT mice expressed higher levels of AKR1A1 than WT mice fed a control diet, and they did not show any noticeable liver steatosis. However, AF-Akr1a1 −/− mice displayed a lower survival rate and more severe liver injury than AF-WT mice, as demonstrated by increased proinflammatory cytokines, oxidative stress, lipid accumulation, fibrosis, and reduced antioxidant enzymes in their livers. Additionally, elevated levels of 4-HNE and p53 phosphorylation were observed in AF-Akr1a1 −/− mice, suggesting that the loss of AKR1A1 led to increased 4-HNE accumulation and subsequent activation of p53, which contributed to the progression of ALD. Furthermore, in AML12 hepatocytes, Akr1a1 knockdown aggravated oxidative stress and steatosis induced by palmitic acid/oleic acid (P/O) inflammation induced by lipopolysaccharide (LPS), and fibrosis induced by TGF-β1. Conclusions This loss-of-function study suggests that AKR1A1 plays a liver-protective role during chronic alcohol consumption by reducing the accumulation of 4-HNE and inhibiting 4-HNE-mediated p53 activation.

Abstract Background Neuroleptospirosis and anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis are both very rare and have only been reported in the form of respective case reports. There are no reports of anti-DPPX encephalitis combined with neuroleptospirosis in the literature. We reported the first case of neuroleptospirosis combined with elevated DPPX antibodies in serum and cerebrospinal fluid (CSF). Case presentation A previously healthy 53-year-old Chinese male farmer with a history of drinking raw stream water and flood sewage exposure was brought to the hospital due to an acute onset of neuropsychiatric symptoms. No fever or meningeal irritation signs were detected on physical examination. Routine laboratory investigations, including infection indicators, leukocyte and protein in CSF, electroencephalogram and gadolinium-enhanced magnetic resonance imaging of the brain, all revealed normal. While metagenomic next-generation sequencing (mNGS) identified the DNA genome of Leptospira interrogans in the CSF. Anti-DPPX antibody was detected both in blood and in CSF. A diagnosis of neuroleptospirosis combined with autoimmune encephalitis associated with DPPX-Ab was eventually made. He resolved completely after adequate amount of penicillin combined with immunotherapy. Conclusion We highlight that in patients with acute or subacute behavioral changes, even in the absence of fever, if the most recent freshwater exposure is clear, physicians should pay attention to leptospirosis. Due to the low sensitivity of routine microscopy, culture, polymerase chain reaction and antibody testing, mNGS may have more advantages in diagnosing neuroleptospirosis. As autoimmune encephalitis can be triggered by various infections, neuroleptospirosis may be one of the causes of autoimmune encephalitis. Since neuronal antibody measurements themselves are not that common in neuroleptospirosis, future studies are needed to determine whether the detection of anti-DPPX antibodies is a rare event in leptospirosis. Early identification of autoimmune encephalitis and timely administration of immunotherapy may lead to a better outcome.