Choriocapillaris reduction accurately discriminates against early-onset Alzheimer's disease.

INTRODUCTION: This study addresses the urgent need for non-invasive early-onset Alzheimer's disease (EOAD) prediction. Using optical coherence tomography angiography (OCTA), we present a choriocapillaris model sensitive to EOAD, correlating with serum biomarkers. METHODS: Eighty-four EOAD patients and 73 controls were assigned to swept-source OCTA (SS-OCTA) or the spectral domain OCTA (SD-OCTA) cohorts. Our hypothesis on choriocapillaris predictive potential in EOAD was tested and validated in these two cohorts. RESULTS: Both cohorts revealed diminished choriocapillaris signals, demonstrating the highest discriminatory capability (area under the receiver operating characteristic curve: SS-OCTA 0.913, SD-OCTA 0.991; P < 0.001). A sparser SS-OCTA choriocapillaris correlated with increased serum amyloid beta (Aß)42, Aß42/40, and phosphorylated tau (p-tau)181 levels (all P < 0.05). Apolipoprotein E status did not affect choriocapillaris measurement. DISCUSSION: The choriocapillaris, observed in both cohorts, proves sensitive to EOAD diagnosis, and correlates with serum Aß and p-tau181 levels, suggesting its potential as a diagnostic tool for identifying and tracking microvascular changes in EOAD. HIGHLIGHTS: Optical coherence tomography angiography may be applied for non-invasive screening of Alzheimer's disease (AD). Choriocapillaris demonstrates high sensitivity and specificity for early-onset AD diagnosis. Microvascular dynamics abnormalities are associated with AD.

Recurrent neural network for predicting absence of heterozygosity from low pass WGS with ultra-low depth.

BACKGROUND: The absence of heterozygosity (AOH) is a kind of genomic change characterized by a long contiguous region of homozygous alleles in a chromosome, which may cause human genetic disorders. However, no method of low-pass whole genome sequencing (LP-WGS) has been reported for the detection of AOH in a low-pass setting of less than onefold. We developed a method, termed CNVseq-AOH, for predicting the absence of heterozygosity using LP-WGS with ultra-low sequencing data, which overcomes the sparse nature of typical LP-WGS data by combing population-based haplotype information, adjustable sliding windows, and recurrent neural network (RNN). We tested the feasibility of CNVseq-AOH for the detection of AOH in 409 cases (11 AOH regions for model training and 863 AOH regions for validation) from the 1000 Genomes Project (1KGP). AOH detection using CNVseq-AOH was also performed on 6 clinical cases with previously ascertained AOHs by whole exome sequencing (WES). RESULTS: Using SNP-based microarray results as reference (AOHs detected by CNVseq-AOH with at least a 50% overlap with the AOHs detected by chromosomal microarray analysis), 409 samples (863 AOH regions) in the 1KGP were used for concordant analysis. For 784 AOHs on autosomes and 79 AOHs on the X chromosome, CNVseq-AOH can predict AOHs with a concordant rate of 96.23% and 59.49% respectively based on the analysis of 0.1-fold LP-WGS data, which is far lower than the current standard in the field. Using 0.1-fold LP-WGS data, CNVseq-AOH revealed 5 additional AOHs (larger than 10 Mb in size) in the 409 samples. We further analyzed AOHs larger than 10 Mb, which is recommended for reporting the possibility of UPD. For the 291 AOH regions larger than 10 Mb, CNVseq-AOH can predict AOHs with a concordant rate of 99.66% with only 0.1-fold LP-WGS data. In the 6 clinical cases, CNVseq-AOH revealed all 15 known AOH regions. CONCLUSIONS: Here we reported a method for analyzing LP-WGS data to accurately identify regions of AOH, which possesses great potential to improve genetic testing of AOH.

Physical and oxidative stability of flaxseed oil-in-water emulsions prepared by natural lignin-carbohydrate complex.

Flaxseed oil, rich in α-linolenic acid, plays a crucial role in various physiological processes. However, its stability presents certain challenges. In this study, the natural lignin-carbohydrate complex (LCC) was used to prepare the physical and oxidative stability of flaxseed oil-in-water emulsions. The LCC was characterized by HPLC, GPC, and FT-IR. The stability of emulsions was evaluated by viscosity, modulus, and micro-morphology changes. Then, the oxidation products were monitored by UV-vis spectrophotometer and HPLC. The results revealed that the high internal phase emulsion (HIPE) was successfully prepared with 2.5 wt% LCC at an oil/water ratio of 75/25 (v/v). Small droplet size (13.361 µm) and high viscosity (36,500 mPa·s) were found even after 30-day storage. Steric interactions of the LCC play a crucial role in ensuring stability, intricately linked to the interfacial properties of the emulsion. Meanwhile, the oxidative stability of α-linolenic acid in the encapsulated flaxseed oil was significantly higher than that in the bulk flaxseed oil. The results revealed that the LCC as a suitable emulsifier opens a new window for the storage of functional lipids rich in polyunsaturated fatty acids.

A rapid and sensitive one-pot platform integrating fluorogenic RNA aptamers and CRISPR-Cas13a for visual detection of monkeypox virus.

The recent global upsurge in Monkeypox virus (MPXV) outbreaks underscores the critical need for rapid and precise diagnostic solutions, particularly in resource-constrained settings. The gold standard diagnostic method, qRT-PCR, is hindered by its time-consuming nature, requirement for nucleic acid purification, expensive equipment, and the need for highly trained personnel. Traditional CRISPR/Cas fluorescence assays, relying on trans-cleavage of ssDNA/RNA reporters labeled with costly fluorophores and quenchers, pose challenges that limit their widespread application, especially for point-of-care testing (POCT). In this study, we utilized a cost-effective and stable fluorogenic RNA aptamer (Mango III), specifically binding and illuminating the fluorophore TO3-3 PEG-Biotin Fluorophore (TO3), as a reporter for Cas13a trans-cleavage activity. We propose a comprehensive strategy integrating RNA aptamer, recombinase-aided amplification (RAA), and CRISPR-Cas13a systems for the molecular detection of MPXV target. Leveraging the inherent collateral cleavage properties of the Cas13a system, we established high-sensitivity and specificity assays to distinguish MPXV from other Orthopoxviruses (OPVs). A streamlined one-pot protocol was developed to mitigate aerosol contamination risks. Our aptamer-coupled RAA-Cas13a one-pot detection method achieved a Limit of Detection (LoD) of 4 copies of target MPXV DNA in just 40 min. Validation using clinical MPX specimens confirmed the rapid and reliable application of our RAA-Cas13a-Apt assays without nucleic acid purification procedure, highlighting its potential as a point-of-care testing solution. These results underscore the user-friendliness and effectiveness of our one-pot RAA-Cas13a-Apt diagnostic platform, poised to revolutionize disease detection and management.

Retreatment with immunotherapy in a patient with hepatocellular carcinoma who received immune checkpoint inhibitors after primary curative treatment: a case report.

Hepatocellular carcinoma (HCC) presents a malignant pathology known for its high early recurrence rate following curative treatment, significantly impacting patient prognosis. Currently, effective strategies to mitigate early HCC recurrence remain undetermined. In this report, we document a case of HCC managed with curative radiofrequency ablation (RFA), particularly in a patient facing a high risk of early recurrence due to a substantial tumor size. In an effort to forestall recurrence, immune checkpoint inhibitors (ICIs) were preemptively administered for 6 months post-RFA. Despite this, early recurrence ensued upon ICIs cessation. Traditionally, the approach to advanced HCC has been conservative, yet recent years have seen promising outcomes with ICIs in advanced HCC. However, research on ICIs retreatment is limited. In the short term, this patient experienced widespread metastases post-ICIs discontinuation, yet exhibited prompt regression upon ICIs reinitiation. Notably, this represents the initial documented instance of employing ICIs to forestall recurrence subsequent to curative RFA in HCC. Following ICIs discontinuation, diffuse recurrence with multiple metastases emerged, with successful resolution upon ICIs retreatment.

A complete oral regimen for induction therapy of patients with high-risk APL: An oral etoposide instead of intravenous infusion for cytoreductive chemotherapy.

There is an urgent need for an oral, efficient and safe regimen for high-risk APL under the pandemic of COVID-19. We retrospectively analysed 60 high-risk APL patients. For induction therapy (IT), in addition to all-trans retinoic acid (ATRA) and oral arsenic (RIF), 22 patients received oral etoposide (VP16) as cytotoxic chemotherapy (CC), and 38 patients received intravenous CC as historical control group. The median dose of oral VP16 was 1000 mg [interquartile rage (IQR), 650-1250]. One patient died during IT in the control group, 59 evaluable patients (100%) achieved complete haematological remission (CHR) after IT and complete molecular remission (CMR) after consolidation therapy. The median time to CHR and CMR was 36 days (33.8-44) versus 35 days (32-42; p = 0.75) and 3 months (0.8-3.5) versus 3.3 months (2.4-3.7; p = 0.58) in the oral VP16 group and in the control group. Two (9.1%) and 3 (7.9%) patients experienced molecular relapse in different group respectively. The 2-year estimated overall survival and event-free survival were 100% versus 94.7% (p = 0.37) and 90.9% versus 89.5% (p = 0.97) respectively. A completely oral, efficient and safe induction regimen including oral VP16 as cytoreductive chemotherapy combined with ATRA and RIF is more convenient to administer for patients with high-risk APL.

Factors associated with discontinuation of treatment for pulmonary arterial hypertension in the United States.

Information on factors leading to pulmonary arterial hypertension (PAH) treatment discontinuation is limited. This study analyzed 12,902 new PAH medication users to identify predictors of treatment discontinuation. Treatment by accredited pulmonary hypertension centers and combination therapy with PAH agents from different classes were less likely to result in discontinuation.

Hereditary and cortical morphological biomarker of sensitivity to reward in short-term withdrawal methamphetamine abusers.

Higher sensitivity to reward (SR) and weaker sensitivity to punishment (SP) construct the fundamental craving characteristics of methamphetamine abuse. However, few studies have appraised relationships between SR/SP (SR or SP) and cortical morphological alterations in methamphetamine abusers and whether hereditary factors take effects on SR/SP is unclear. Based on surface-based morphometric analysis, cortical discrepancy was investigated between 38 methamphetamine abusers and 37 healthy controls. Within methamphetamine abusers, correlation profiling was performed to discover associations among aberrant neuroimaging substrates, SR, SP, and craving. According to nine single nucleotide polymorphism sites of dopamine-related genes, we conducted univariate general linear model to find different effects of genotypes on cortical alterations and SR/SP/craving (SR, SP, or craving). Ultimately, mediation analyses were conducted among single nucleotide polymorphism sites, SR/SP/craving, and cortical morphological alterations to discover their association pathways. Compared to healthy controls, thinner cortices in inferior temporal gyrus, lateral orbitofrontal cortex, medial orbitofrontal cortex, inferior parietal lobule, and lateral occipital cortex in the left hemisphere were found in methamphetamine abusers (P < 0.05, family-wise error corrected). Cortical thickness in the inferior temporal gyrus was negatively correlated with SR scores. We found that rs1800497 A-containing genotypes had lower cortical thickness in the left inferior parietal lobule than the GG genotype. The rs5751876 had effects on SR scores. This study would provide convincing biomarkers for SR in methamphetamine abusers and offer potential genetic targets for personalizing relapse prevention.

Evaluation of antibacterial activity and influencing factors of normal and nanostructured copper-based materials.

Background: Copper-based materials have garnered extensive recognition for their effective nature against microorganisms and their minimal toxicity. However, the evaluation for their antibacterial activity is still in its nascent stages, and the evaluation results based on existing criteria are not representative of real-world application. Aim: To evaluate the antibacterial activity and primary determinants of influence of copper-based materials in order to investigate their practical antibacterial activity and potential mechanisms of such materials. Methods: Staphylococcus aureus and Escherichia coli bacterial suspensions were applied via inoculation onto the surfaces of normal and nanostructured copper foil. Following incubation of the inoculated surfaces under diverse experimental conditions-including varying compositions of the bacterial suspension, the use of chemical neutralizers, the existence of organic interferents, and low temperature and humidity-surviving bacteria were enumerated. Using the scanning electron microscopy and X-ray photoelectron spectroscopy, the surface changes of copper-based materials were examined. Findings: Following 1 h of exposure to 37 °C and 90% relative humidity, Staphylococcus aureus was reduced by 4.45 log10 on normal copper foil, while all of the bacteria were eradicated on nanostructured copper foil. In addition, it was discovered that preparing a bacterial suspension with PBS results in a significant number of Escherichia coli fatalities during the test, whereas using TPS promotes the bacteria's normal growth. Furthermore, the outcomes of the antibacterial activity test were diminished when chemical neutralization was employed, and the presence of organic interferents had distinct impacts on normal copper foil and nanostructured copper foil. Additionally, low temperatures and humidity diminished the antibacterial activity of copper foil, whereas normal copper foil produced significantly better results. Conclusion: While copper-based materials exhibit robust antibacterial activity as determined by standard assays, their efficacy in real-world applications is subject to various influencing mechanisms. In order to objectively evaluate the antibacterial activity of copper-based materials and provide precise guidance for their development and practical application, it is essential to regulate test conditions with targeted.

[Effect of recombinant human thrombopoietin on platelets in rats with D-galactosamine salt-induced acute liver failure].

OBJECTIVE: To evaluate the effects of recombinant human thrombopoietin (rhTPO) on platelet count (PLT) and liver function in acute liver failure (ALF) rats by observing the dynamic changes of PLT, thrombopoietin (TPO) and liver function during ALF. METHODS: Twenty-four male Sprague-Dawley (SD) rats were divided into model group, TPO group and interleukin-11 (IL-11) group using a random number table method, with eight rats in each group. All rats were intraperitoneally injected with D-galactosamine (D-GalN, 1 500 mg/kg, dosed within 72 hours) to induce the ALF model. After modeling, rats in TPO group was received subcutaneous injection of 15 µg/kg of rhTPO for 5 days, and rats in IL-11 group was received subcutaneous injection of 0.45 mg/kg of IL-11 for 5 days. Venous blood samples were collected before and at 1, 3, 5, 7 and 12 days after molding for whole blood cell detection. The level of TPO in serum was detected by enzyme-linked immunosorbent assay (ELISA). Liver function indexes including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) and albumin (ALB) were measured before and at 1, 3 and 5 days after modeling. The rats were sacrificed 12 days after the modeling, and the pathological changes of liver tissue were observed by hematoxylin-eosin (HE) staining. RESULTS: Two rats in each group died within 24-48 hours after modeling. HE staining showed that all three groups of ALF rats showed large flake necrosis of hepatocytes, disorder of hepatic lobular structure, mesh scaffold collapse, hepatic sinus congestion and hemorrhage, and flake infiltration of inflammatory cells on day 12 after modeling. The levels of serum ALT, AST and TBil of rats in each group were significantly increased 1 day after modeling and then decreased. The level of ALB decreased significantly on the first day after modeling and then increased, but there was no significant difference in the trend of liver function indexes among the three groups. PLT in the three groups decreased rapidly on day 1 after modeling, and then recovered gradually with the improvement of liver function. The PLT of the TPO group rose to the peak value 7 days after molding and was significantly higher than that of the model group [PLT (×109/L): 1 673.3±347.5 vs. 855.3±447.0, P < 0.05], while there was no significant difference between the IL-11 group and the model group [PLT (×109/L): 1 350.3±386.6 vs. 855.3±447.0, P > 0.05]. The level of serum TPO of the three groups increased significantly on day 1 after modeling, then decreased, and dropped to the lowest value on day 5, but there was no significant difference in the trend of serum TPO level among the three groups. CONCLUSIONS: PLT in ALF rats decreased rapidly in the early stage and recovered gradually with the improvement of liver function, and the serum TPO level increased first and then decreased. Injection of rhTPO can significantly increase PLT in ALF rats, but has no significant effect on liver function and survival rate.

Hepatomegaly and jaundice as the presenting symptoms of systemic light-chain amyloidosis: A case report.

BACKGROUND: Light chain (AL) amyloidosis is a plasma cell dyscrasia characterized by the pathologic production and extracellular tissue deposition of fibrillar proteins derived from immunoglobulin AL fragments secreted by a clone of plasma cells, which leads to progressive dysfunction of the affected organs. The two most commonly affected organs are the heart and kidneys, and liver is rarely the dominant affected organ with only 3.9% of cases, making them prone to misdiagnosis and missed diagnosis. CASE SUMMARY: A 65-year-old woman was admitted with a 3-mo history of progressive jaundice and marked hepatomegaly. Initially, based on enhanced computed tomography scan and angiography, Budd-Chiari syndrome was considered and balloon dilatation of significant hepatic vein stenoses was performed. However, additional diagnostic procedures, including liver biopsy and bone marrow-examination, revealed immunoglobulin kapa AL amyloidosis with extensive liver involvement and hepatic vascular compression. The disease course was progressive and fatal, and the patient eventually died 5 mo after initial presentation of symptoms. CONCLUSION: AL amyloidosis with isolated liver involvement is very rare, and can be easily misdiagnosed as a vascular disease.

Full-term pregnancy with retroperitoneal giant mucinous cyst: A case report and literature review.

RATIONALE: Retroperitoneal benign cysts during pregnancy are extremely rare and often remain asymptomatic until they attain a very large size. Diagnosis typically relies on a pathological tissue biopsy. The decision to pursue 1-step or 2-step surgical treatment should be tailored to each individual case rather than generalized. PATIENT CONCERNS: This case report presents the unique scenario of a pregnant woman with a confirmed pregnancy complicated by a large retroperitoneal cyst. The patient had a retroperitoneal cyst during her initial pregnancy, which went undetected during the first cesarean section. However, it was identified during her second pregnancy by which time it had grown to 13.0 cm × 15.0 cm × 25.0 cm, and extended from the liver margin to right ovarian pelvic infundibulopelvic ligament. Consequently, it was removed smoothly during her second cesarean section. DIAGNOSES: Postoperative pathology results indicated a massive retroperitoneal mucinous cystadenoma. INTERVENTIONS: The giant retroperitoneal cyst was smoothly excised during the second cesarean delivery for 1-step surgical treatment. OUTCOMES: Under the combined spinal and epidural anesthesia, a live female infant was delivered at 38 3/7 gestational weeks and the neonatal weight was 3200g. Under general anesthesia with endotracheal intubation, the giant retroperitoneal cyst was excised smoothly without complications. LESSONS: The findings of this case report contribute to the understanding of the diagnostic modalities, surgical approaches and postoperative considerations of giant retroperitoneal cysts associated with pregnancy.

Clinical characteristics and prognosis of acute myeloid leukemia patients with Runt-related transcription factor 1 mutation: A single-center retrospective analysis.

This study aimed to investigate the clinical characteristics and prognosis of Runt-related transcription factor 1 (RUNX1) mutant acute myeloid leukemia (AML) patients by comparing the features of AML patients with or without RUNX1 mutation. We retrospectively analyzed 180 AML patients including 36 AML patients with mutant RUNX1(AML-RUNX1mut ) and 144 AML patients with wild-type RUNX1(AML-RUNX1wt ) were selected using the case-pair method(1:4). Compared to AML-RUNX1wt , AML-RUNX1mut showed higher frequency of ASXL1 (p < 0.001), SRSF2 (p < 0.001), BCORL1 (p < 0.001), RAS (p = 0.010) mutations, and absent NPM1 mutations (p = 0.022). The 3-year overall survival (OS) and disease-free survival (DFS) of AML-RUNX1mut and AML-RUNX1wt were 73.1% versus 68.0% (p = 0.64) and 80.7% versus 71.6% (p = 0.37), respectively. AML-RUNX1mut receiving allogeneic hematopoietic cell transplantation (allo-HSCT) showed better survival than those who did not receive allo-HSCT (3-year OS, 84.3% vs. 52.7%; p = 0.006). Multivariate analysis showed that EZH2 mutation (p = 0.003), white blood cell (WBC) ≥30 × 109 /L (p = 0.036) and age ≥60 years (p = 0.038) were significant independent risk factors for inferior OS of AML-RUNX1mut ; WBC ≥30 × 109 /L (p = 0.013) and DNMT3A mutation (p = 0.045) were significant independent risk factors for shorter DFS of AML-RUNX1mut . In conclusion, AML-RUNX1mut showed unique clinical characteristics, but the survival between AML-RUNX1mut and AML-RUNX1wt were comparable. EZH2 co-mutation, DNMT3A co-mutation, old age and high WBC count were associated with inferior survival of AML-RUNX1mut . Allo-HSCT can significantly improve the prognosis of AML-RUNX1mut .

Successful Retrieval of a Broken Aspiration Needle Penetrated into the Right Pulmonary Artery: A Case Report with Experience Sharing.

INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration is increasingly used as a minimally invasive procedure in clinical settings. It is generally regarded as a safe procedure with high diagnostic accuracy. However, a complication involving a needle fracture that penetrated a nearby artery has not been reported during this procedure. CASE PRESENTATION: A male patient, 58 years of age, underwent endobronchial ultrasound-guided transbronchial needle aspiration for a mediastinal lymph node biopsy at a local hospital. The aspiration needle fractured and penetrated from the right middle segmental bronchus into the right pulmonary artery. The patient was then transferred to our hospital. After conducting repeated chest imaging examinations to confirm the presence of the foreign body and holding multidisciplinary team consultations, we first inserted a deflated balloon catheter near the puncture site in the right middle segmental bronchus. Following the needle retrieval through a flexible bronchoscope, the balloon catheter was inflated to ensure local hemostasis. Follow-up evaluations revealed no further complications for this patient. CONCLUSION: Intragenic vascular injury can occur during endobronchial ultrasound-guided transbronchial needle aspiration. Careful pre-procedure preparations should be planned to minimize complications. In patients experiencing complications due to needle penetration, consultation and coordination with a multidisciplinary team are essential to ensure the safe retrieval of the broken needle.

Longitudinal associations between serum IL-34 with severity and prognosis in community-acquired pneumonia patients.

BACKGROUND: Interleukin-34 (IL-34) is a hematopoietic cytokine and a ligand of colony-stimulating factor 1 receptor (CSF-1R). Numerous studies have demonstrated that IL-34 is involved in several inflammatory diseases. Nevertheless, the role of IL-34 is obscure in community-acquired pneumonia (CAP) patients. This research aimed to assess the associations of serum IL-34 with severity and prognosis in CAP patients through a longitudinal study. METHODS: CAP patients and healthy volunteers were recruited. Peripheral blood samples were collected. Serum IL-34 and inflammatory cytokines were tested by enzyme linked immunosorbent assay (ELISA). Demographic characteristics and clinical information were acquired through electronic medical records. RESULTS: Serum IL-34 was elevated in CAP patients compared with healthy volunteers. The content of serum IL-34 was gradually upregulated with increased CAP severity scores. Mixed logistic and linear regression models suggested that serum IL-34 elevation was associated with increased PSI and SMART-COP scores. Correlative analysis found that serum IL-34 was positively correlated with inflammatory cytokines among CAP patients. A longitudinal study indicated that higher serum IL-34 at admission elevated the risks of mechanical ventilation and death during hospitalization. Serum IL-34 had a higher predictive capacity for death than CAP severity scores. CONCLUSION: There are prominently positive dose-response associations between serum IL-34 at admission with the severity and poor prognosis, suggesting that IL-34 is implicated in the occurrence and development of CAP. Serum IL-34 may serve as a biomarker to forecast disease progression and poor prognosis in CAP patients.

Effects of the excitation wavelength and temperature on the zero-phonon emission line of Cr:YAG.

In this work, a detailed study was conducted of the temperature and excitation wavelength-dependent photoluminescence (PL) spectra of the chromium-doped yttrium aluminum garnet (Cr:YAG) transparent ceramic. Focusing on the two sets of zero-phonon lines (ZPLs) of the 2 E→4 A 2 transition in this material, the PL spectra are discovered to evolve significantly with respect to temperature and be highly dependent on the excitation wavelength. Compared to the continuous variation behavior with temperature, an increase in the excitation wavelength leads to a blueshift of the peak position within the regions of 450 nm to 465 nm, 465 nm to 490 nm, and 490 nm to 500 nm, and a sharp change in the PL position at the excitation wavelengths of 465 nm and 490 nm. The electron-phonon coupling (EPC) effect is believed to be more sensitive to the excitation wavelength. Different excitation wavelengths involve different electronic levels participating in the light emission processes, which explains the evolution behavior of the PL peak position with respect to the excitation wavelength. Moreover, the emergence of weak peaks next to the ZPLs at particular temperatures and excitation wavelengths is also observed. This work compares the influence of the temperature and excitation wavelength to the PL properties of the Cr:YAG transparent ceramic, which promotes an advanced understanding of the luminescence behavior of the Cr:YAG transparent ceramics.

Polysaccharide Isolated from Agaricus blazei Murill Alleviates Intestinal Ischemia/Reperfusion Injury through Regulating Gut Microbiota and Mitigating Inflammation in Mice.

Intestinal ischemia-reperfusion (I/R) injury is a serious disease in medical settings, and gut dysbiosis is a major contributor to its development. Polysaccharides from Agaricus blazei Murill (ABM) showed a range of pharmacological activities, yet no studies assessed the potential of ABM polysaccharides for alleviating intestinal I/R injury. Here, we purified a major polysaccharide (ABP1) from an ABM fruit body and subsequently tested its potential to mitigate intestinal I/R injury in a mouse model of temporary superior mesenteric artery occlusion. The results reveal that ABP1 pretreatment enhances gut barrier function via upregulation of the expression of tight junction proteins such as ZO-1 and occludin. Additionally, ABP1 intervention reduces the recruitment of neutrophils and the polarization of M1 macrophages and limits inflammation by blocking the assembly of the NLRP3 inflammasome. Moreover, the role of ABP1 in regulating the gut microbiota was confirmed via antibiotic treatment. The omics data reveals that ABP1 reprograms gut microbiota compositions, characterized by a decrease of Proteobacteria and an increase of Lachnospiraceae and Lactobacillaceae, especially the SCFA-producing genera such as Ligilactobacillus and Blautia. Overall, this work highlights the therapeutic potential of ABP1 against intestinal I/R injury, which mainly exhibits its effects via regulating the gut microbiota and suppressing the overactivated inflammation response.

The genetic susceptibility analysis of TAAR1 rs8192620 to methamphetamine and heroin abuse and its role in impulsivity.

Abnormal genetic polymorphism of trace amine-associated receptor 1 (TAAR1) rs8192620 site has been confirmed to induce methamphetamine (MA) use and drug craving. However, the genetic susceptibility difference between MA addicts and heroin addicts is unknown. This study evaluated genetic heterogeneity of TAAR1 rs8192620 between MA and heroin addicts and elucidated whether rs8192620 genotypes associated with discrepancy in emotional impulsivity, which would help to instruct individualized treatment in addiction via acting on TAAR1 and evaluate risk of varied drug addiction. Participants consisting of gender-matched 63 MA and 71 heroin abusers were enrolled in the study. Due to mixed drug usage in some MA addicts, MA users were further subdivided into 41 only-MA (only MA taking) and 22 mixed-drug (Magu composed of about 20% MA and 70% caffeine) abusers. Via inter-individual single nucleotide polymorphism (SNP) analysis and two-sample t tests, respectively, the genotypic and Barratt Impulsiveness Scale-11 (BIS-11) scores differences between groups were completed. With following genotypic stratification, the differences in BIS-11 scores between groups were analyzed through two-sample t test. Individual SNP analysis showed significant differences in alleles distribution of rs8192620 between MA and heroin subjects (p = 0.019), even after Bonferroni correction. The TT homozygotes of rs8192620 dominated in MA participants, while C-containing genotypes in heroin (p = 0.026). There was no association of genotypes of TAAR1 rs8192620 with addicts' impulsivity. Our research indicates that the TAAR1 gene polymorphism might mediate the susceptibility discrepancy between MA and heroin abuse.

Drinking water quality evaluation in supply systems in Wuhan, China: application of entropy weight water quality index and multivariate statistical analysis.

In this study, source water, finished water, and tap water were sampled monthly from two large drinking water treatment plants in Wuhan city, China for 12 months where physicochemical and microbiological parameters were measured, and the complex monitoring data was analyzed using single-factor assessment method, entropy weight water quality index (EWQI), and multivariate statistical techniques (i.e., cluster analysis (CA), discriminant analysis, and correlation analysis). The results of the single-factor assessment method showed that the total nitrogen pollution was the main problem in the source water quality, and the finished and tap water met the required quality standards. The EWQI values indicated that the overall quality of the source, finished, and tap water samples was "Excellent." In addition, strengthening monitoring of parameters with high entropy weights, including Pb, Hg, sulfide, Cr in surface water and Hg, aerobic bateria count, and As in drinking water, were suggested, as they were prone to drastic changes. Spatial CA grouped the finished and tap water samples from the same plant into a cluster. Temporal CA grouped 12 sampling times of source water into Cluster 1 (June), Cluster 2 (April-May, and July-November), and Cluster 3 (December-March). Concerning finished and tap water, except the October was regrouped, the result of temporal CA was consistent to that of the source water. Based on similar characteristics of water samples, monitoring sites and frequency can be optimized. Moreover, stepwise discriminant analysis indicated that the spatiotemporal variations in water quality among CA-groups were enough to be explained by four or five parameters, which provided a basis for the selection of monitoring parameters. The results of correlation analysis showed that few pairwise correlations were both significant (P < 0.05) and stable across sampling sites, suggesting that the number of monitoring parameters was difficult to reduce through substitution. In summary, this study illustrates the usefulness of EWQI and the multivariate statistical techniques in the water quality assessment and monitoring strategy optimization.

A Minimized Measurement Scheme for Predicting HbA1c Using Discrete Self-Monitoring Blood Glucose Data Within 4 Weeks for People with Type 2 Diabetes.

Objective: To establish an accurate and robust calculation model for predicting hemoglobin A1c (HbA1c) for people with type 2 diabetes (T2D) by using the fewest discrete blood glucose values according to an irregular data set and propose an appropriate cost-effective and scientific scheme for routine blood glucose monitoring. Methods: By using two data sets obtained from 2017 to 2022, which involved 2432 people with T2D, ∼420,000 irregular blood glucose values, and 10,000 HbA1c values, multiple blood glucose monitoring schemes were designed and compared to find the optimal one. The data were structured and then fitted using a regularized extreme learning machine, and the results were evaluated on the basis of indicators such as mean absolute error (MAE), root mean square error, and the relevance analysis (R) value; the optimal scheme for routine blood glucose monitoring was determined by combining the accuracy and the cost and was compared with previous studies in terms of accuracy and stability. Results: Data fitting results for the chosen scheme: R = 0.8029 (P < 0.001), MAE = 0.3181% (95% confidence interval, 0.2666-0.3695%). Within the last 4 weeks before the prediction of HbA1c, a minimum of only seven fasting and seven postprandial blood glucose values are needed, of which are one fasting and one postprandial blood glucose values per 4 days. Compared with previous studies, the prediction model shows better accuracy and stability (P < 0.05), especially under the great glucose fluctuation group. Conclusion: A minimized calculation model for accurately and robustly predicting HbA1c using discrete self-monitoring of blood glucose data within 4 weeks for people with T2D has been established and provides a new reference for the design of a scheme for blood glucose monitoring. The diabetes care clinic of Peking University First Hospital (Registration Number: ChiCTR2300068139).