Search

Deposition of insoluble SOD1 aggregates in motor neurons is the hallmark of SOD1-associated ALS. Mutant SOD1 protein promotes structural instability that leads to misfolded SOD1 protein aggregates, which can be recapitulated in vitro. Therefore, aggregation propensity in cell lines can be a reliable indicator for the pathogenicity classification of SOD1 variants. Herein, we performed in vitro experiment to classify the pathogenicity of 34 SOD1 variants of uncertain significance (VUS) from 215 variants reported previously. The clinical features of 234 ALS patients with 31 SOD1 likely pathogenic (LP) variants were summarized. 31 VUS variants formed aggregates spontaneously, indicating LP variants. Missense variants were mainly located in the C-terminal of SOD1. Among patients with 31 SOD1 LP variants, 75% of patients had lower limb onset. The onset of familial ALS patients (45.7±14.0 years) is earlier than sporadic ALS patients (50.6±13.1 years). Our results expand the spectrum of SOD1 mutations and highlight the natural history of SOD1-positive ALS patients for further clinical trials in SOD1-related ALS.

Meta-analysis results showed that dietary phytosterols can help reduce TC and LDL-C concentrations in hypercholesterolemia patients without affecting HDL-C and TG, which were related to many factors. Dose is an important factor affecting LDL-C level.

Melanocortin 3 and 4 receptors are two important neural G protein-coupled receptors that regulate energy homeostasis in vertebrates. Melanocortin receptor accessory protein 2 (MRAP2) is also involved in the regulation of food intake and body weight as a variable regulator of melanocortin receptors. Rainbow trout (Oncorhynchus mykiss) is a valuable cold-water fish cultured worldwide. In the rainbow trout model, we cloned and identified mrap2a, a paralog of mrap2. Rainbow trout mrap2a consisted of a 690 bp ORF and was expected to encode a putative protein of 229 amino acids. The qPCR results showed that rainbow trout mrap2a was expressed at high levels in brain tissue similar to mc3r and mc4r. In addition, co-immunoprecipitation verified that MRAP2a interacts with MC3R and MC4R in vitro and that MRAP2a is involved in and regulates the constitutive activity and signaling of MC3R and MC4R. MRAP2a reduced constitutive and agonist-stimulated cAMP levels of MC3R; furthermore, MRAP2a increased constitutive ERK1/2 activation but reduced ligand-induced stimulation at high levels of expression. For MC4R, MRAP2a showed decreased cAMP basal activity but increased agonist-stimulated cAMP signaling and increased ACTH ligand sensitivity. However, MRAP2a failed to affect MC4R constitutive activity and agonist-induced ERK1/2 signaling. Undoubtedly, our study will have great significance for revealing the conserved role of MC4R and MC3R signaling in teleost fish, especially in cold-water fish growth and energy homeostasis.

In this review, we will summarize the effects of these perioperative anesthetics and anesthetic interventions on the immune system and tumorigenesis as well as address the related clinical evidence on cancer-related mortality and recurrence.Cancer remains a leading cause of morbidity and mortality worldwide. For many solid tumors, surgery is one of the major therapies. Unfortunately, surgery promotes angiogenesis, shedding of circulating cancer cells, and suppresses immunity. Hence, the perioperative period has a close relationship with cancer metastases or recurrence. In the perioperative period, patients require multiple anesthetic management including anesthetics, anesthetic techniques, and body temperature control. Preclinical and retrospective studies have found that these anesthetic agents and interventions have complex effects on cancer outcomes. Therefore, well-planned, prospective, randomized controlled trials are required to explore the effects of different anesthetics and techniques on long-term outcomes after cancer surgery. Due to the conflicting effects of anesthetic management on cancer recurrence, further preclinical and clinical trials are required and beneficial to the development of systemic cancer therapies.

Liver cancer as the main leading cancer has caused heavy burdens globally. The prognosis of liver cancer is closely related with postoperative nutrition support. Corn oligopeptides (COPs) are protein hydrolysates produced by enzymatic treatments, which have shown potential bioactivities, such as inhibiting angiotensin I-converting enzyme, resisting lipid peroxidation and anti-oxidant. However, the correlation between COPs and liver cancer patients is still unknown and the potential mechanism of COPs on liver cancer is unclear as well. The aim of this study was to assess effects of 7-day intervention of COPs after surgery on liver function and serum metabolic profiles of liver cancer patients.Patients were assigned into COPs intervention group (n=50) and control group (n=91) for 7 days. Investigations were scheduled at 1Seven-day supplementation of COPs on early post-surgery liver cancer patients down-regulated levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin and up-regulated prothrombin time activity and prealbumin levels. LC/MS analysis revealed metabolic signatures including regulation of 16 metabolites, which was closely related with two metabolic pathways (nicotinate and nicotinamide metabolism, fatty acid metabolism).COPs supplementation has displayed the potentials on alleviating the injury of liver function and it may be due to regulation of fatty acid metabolism, nicotinate and nicotinamide metabolism, lipid peroxidation and anti-inflammatory action. More researches are warranted in future to confirm the exact mechanisms.

Phosphoenolpyruvate/phosphate translocator (PPT) transports phosphoenolpyruvate from the cytosol into the plastid for fatty acid (FA) and other metabolites biosynthesis.This study investigated PPTs' functions in plant growth and seed oil biosynthesis in oilseed crop Brassica napus.We created over-expression and mutant material of BnaPPT1. The plant development, oil content, lipids, metabolites and ultrastructure of seeds were compared to evaluate the gene function.The plastid membrane localized BnaPPT1 was found to be required for normal growth of B. napus. The plants grew slower with yellowish leaves in BnaA08.PPT1 and BnaC08.PPT1 double mutant plants. The results of chloroplast ultrastructural observation and lipid analysis show that BnaPPT1 plays an essential role in membrane lipid synthesis and chloroplast development in leaves, thereby affecting photosynthesis. Moreover, the analysis of primary metabolites and lipids in developing seeds showed that BnaPPT1 could impact seed glycolytic metabolism and lipid level. Knockout of BnaA08.PPT1 and BnaC08.PPT1 resulted in decreasing of the seed oil content by 2.2 to 9.1%, while overexpression of BnaC08.PPT1 significantly promoted the seed oil content by 2.1 to 3.3%.Our results suggest that BnaPPT1 is necessary for plant chloroplast development, and it plays an important role in maintaining plant growth and promoting seed oil accumulation in B. napus.

Wenchengia alternifolia C.Y. Wu & S. Chow (Lamiaceae), the sole species of the genus Wenchengia C.Y. Wu & S. Chow, is extremely rare and is currently listed as Critically Endangered (CR) on the IUCN Red List. The species had long been considered endemic to Hainan Island, China and was once believed to be extinct until a small remnant population was rediscovered at the type locality in 2010. Four more populations were later found on Hainan and in Vietnam. In order to develop genomic resources for further studies on population genetics and conservation biology of this rare species, we identified infraspecific molecular markers in the present study, using genome skimming data of five individuals collected from two populations on Hainan Island and three populations in Vietnam respectively. The length of plastome of the five individuals varied from 152,961 bp to 150,204 bp, and exhibited a typical angiosperm quadripartite structure. Six plastid hotspot regions with the Pi > 0.01 (trnH-psbA, psbA-trnK, rpl22, ndhE, ndhG-ndhI and rps15-ycf1), 1621 polymorphic gSSRs, as well as 1657 candidate SNPs in 237 variant nuclear genes were identified, thereby providing important information for further genetic studies.

In brief Insufficient trophoblast invasion at the maternal–fetal interface contributes to abortion-prone pregnancy. Our study shows that decreased levels of IGFBP7 in unexplained recurrent spontaneous abortion (URSA) trophoblast cells inhibit MMP2 and Slug expression as well as trophoblast invasion, suggesting that IGFBP7 should be considered a potential therapeutic protein target in URSA. Abstract Insufficient trophoblast invasion at the maternal–fetal interface contributes to abortion-prone pregnancy. Cyclosporine A (CsA) can exert therapeutic effects on URSA by promoting trophoblast invasion. A previous study showed decreased expression of insulin-like growth factor-binding protein 7 (IGFBP7) in the sera of recurrent spontaneous abortion patients. However, the role of IGFBP7 in URSA remains unknown. The aim of this study was to determine whether IGFBP7 modulates trophoblast invasion in URSA and the underlying molecular mechanisms. We found that IGFBP7 was expressed at lower levels in villous specimens from URSA patients. Manipulating IGFBP7 expression significantly affected the MMP2 and Slug expression in HTR-8/SVneo cells as well as trophoblast invasion in vitro. Inactivation of IGF-1R by IGFBP7 was observed, and IGF-1R inhibition increased the IGFBP7-induced MMP2 and Slug expression in HTR-8/SVneo cells. Moreover, the level of c-Jun was significantly upregulated in the URSA group. Silencing IGFBP7 increased the binding of downstream c-Jun to the MMP2 and Slug promoter regions in HTR-8/SVneo cells, thus suppressing transcription. In addition, increased expression of IGFBP7 in HTR-8/SVneo cells was observed upon CsA treatment. Knockdown of IGFBP7 inhibited the CsA-enhanced MMP2 and Slug expression in HTR-8/SVneo cells. Our results suggest that in normal pregnancy, IGFBP7 induces MMP2 and Slug expression via the IGF-1R-mediated c-Jun signaling pathway, thereby promoting trophoblast invasion. IGFBP7 depletion in URSA inhibits MMP2 and Slug expression as well as trophoblast invasion. Moreover, IGFBP7 participates in CsA-induced trophoblast invasion, suggesting that IGFBP7 is a potential therapeutic target for URSA.

The Alfin-like (AL) family is a group of small plant-specific transcriptional factors involved in abiotic stresses in dicotyledon. In an early study, we found an AL gene in rice that was associated with grain yield under drought stress. However, little information is known about the AL family in rice. In this study, AL genes in the rice genome were identified, and the OsAL proteins were found to locate in the nucleus and have no transcriptional self-activation activity. The expression of the OsALs was regulated by different environmental stimulations and plant hormones. Association and domestication analysis revealed that natural variation of most OsALs was significantly associated with yield traits, drought resistance and divergence in grain size in indica and japonica rice varieties. Hap1 of OsAL7.1 and Hap7 of OsAL11 were favorable haplotypes of seed weight and germination under osmotic stress. Furthermore, osal7.1 and osal11 mutants have larger seeds and are more sensitive to abscisic acid and mannitol during germination stage. Overexpressing of OsAL7.1 and OsAL11 in rice weakened the tolerance to drought in the adult stage. Thus, our work provides informative knowledge for exploring and harnessing haplotype diversity of OsALs to improve yield stability under drought stress.

Phototheranostics that integrates real-time optical imaging and light-controlled therapy has recently emerged as a promising paradigm for cancer theranostics. Herein, a new small molecule dye DPP-BT-TPA with strong emission above 1000 nm and a redox-responsive prodrug camptothecin-combretastatin A4 (CPT-CA4) were designed and successfully synthesized. A multifunctional phototheranostic nanoplatform was then fabricated by encapsulating them within an amphiphilic polymer. The presence of DPP-BT-TPA enabled high-resolution imaging in the second near-infrared window (NIR-II) and efficient photothermal therapy. The prodrug was cleaved by the overexpressed glutathione (GSH) in the tumor microenvironment to release the chemotherapeutic drug CPT and the angiogenesis inhibitor CA4. Because this process can be accelerated with elevated temperature, laser-induced hyperthermia was utilized to control the drug release and enhance the therapeutic effect. Tumors in living mice were observed through NIR-II imaging after intravenous injection of the obtained nanoparticles. Improved antitumor efficacy by photothermal/chemo/antiangiogenic combination therapy was achieved with a NIR laser both in vitro and in vivo. This work provides a promising strategy for developing tumor microenvironment responsive and light-controlled theranostic platforms. STATEMENT OF SIGNIFICANCE: Fluorescence imaging in the second near-infrared (NIR-II, 1000-1700 nm) window and near-infrared light-controlled drug release have been recognized as efficient strategies for cancer theranostics. Herein, we present a phototheranostic platform fabricated with a biocompatible NIR-II emissive dye DPP-BT-TPA and a redox-responsive prodrug camptothecin-combretastatin A4 (CPT-CA4). DPP-BT-TPA not only provides high-resolution NIR-II imaging in vivo but also enables efficient photothermal therapy. In addition, the photothermal effect largely accelerates the release of the chemotherapeutic drug CPT and the angiogenesis inhibitor CA4 in the glutathione-overexpressed tumor microenvironment. Thus, the designed phototheranostic platform can be used for NIR-II imaging-guided photothermal/chemo/antiangiogenic combination therapy for tumors with a single laser.

BACKGROUND: Early identification of metabolic-associated fatty liver disease (MAFLD) is urgent. Atherogenic index of plasma (AIP) is a reference predictor of obesity-related diseases, but its predictive value for MAFLD remains unclear. No studies have reported whether its combination with waist circumference (WC) and body mass index (BMI) can improve the predictive performance for MAFLD. AIM: To systematically explore the relationship between AIP and MAFLD and evaluate its predictive value for MAFLD and to pioneer a novel noninvasive predictive model combining AIP, WC, and BMI while validating its predictive performance for MAFLD. METHODS: This cross-sectional study consecutively enrolled 864 participants. Multivariate logistic regression analysis and receiver operating characteristic curve were used to evaluate the relationship between AIP and MAFLD and its predictive power for MAFLD. The novel prediction model A-W-B combining AIP, WC, and BMI to predict MAFLD was established, and internal verification was completed by magnetic resonance imaging diagnosis. RESULTS: Subjects with higher AIP exhibited a significantly increased risk of MAFLD, with an odds ratio of 12.420 (6.008-25.675) for AIP after adjusting for various confounding factors. The area under receiver operating characteristic curve of the A-W-B model was 0.833 (0.807-0.858), which was significantly higher than that of AIP, WC, and BMI (all P < 0.05). Subgroup analysis illustrated that the A-W-B model had significantly higher area under receiver operating characteristic curves in female, young and nonobese subgroups (all P < 0.05). The best cutoff values for the A-W-B model to predict MAFLD in males and females were 0.5932 and 0.4105, respectively. Additionally, in the validation set, the area under receiver operating characteristic curve of the A-W-B model to predict MAFLD was 0.862 (0.791-0.916). The A-W-B level was strongly and positively associated with the liver proton density fat fraction (r = 0.630, P < 0.001) and significantly increased with the severity of MAFLD (P < 0.05). CONCLUSION: AIP was strongly and positively associated with the risk of MAFLD and can be a reference predictor for MAFLD. The novel prediction model A-W-B combining AIP, WC, and BMI can significantly improve the predictive ability of MAFLD and provide better services for clinical prediction and screening of MAFLD.

Objective: To investigate the effectiveness of applying a multidisciplinary collaborative model for the diagnosis and treatment of patients with vertigo. Methods: The study was carried out in Xianyang Hospital of Yan’an University, in which 100 patients with vertigo were selected from April 2021 to April 2022 and were divided into two groups: the control group was under the single diagnosis and treatment model, whereas the experimental group was under the multidisciplinary collaborative diagnosis and treatment model, with 50 cases in each group. The diagnostic effects of the two groups were compared. Results: The diagnostic and therapeutic efficiency of the patients in the experimental group were 94% and 98%, respectively, while those of the patients in the control group were 78% and 82%, respectively, with a significant difference between the two groups (p < 0.05). The balance scores of the patients in both groups were low before the treatment, in which the difference was not significant (p > 0.05); after the treatment, the scores improved, with those of the patients in the experimental group being significantly higher than those in the control group (p < 0.05). Moreover, the satisfaction rate of patients in the experimental group (98%) was significantly higher than that of the control group (80%) (p < 0.05). Conclusion: The application of the multidisciplinary collaborative diagnosis and treatment model in the diagnosis of patients with vertigo is effective. The multidisciplinary model can improve clinical diagnosis, enhance the treatment effect, improve the clinical symptoms of patients, and increase the satisfaction of patient care. Hence, it is of high clinical application value.

Masked hypertension is difficult to identify and is associated with adverse outcomes. How and to what extent masked hypertension is related to overweight and obesity remain unclear. In participants with a clinic blood pressure (BP) 140/90 mmHg enrolled in a nationwide prospective registry in China, we performed ambulatory and home BP measurements and defined masked hypertension and masked uncontrolled hypertension as an elevated 24-h (≥130/80 mmHg), daytime (≥135/85 mmHg) or nighttime ambulatory BP (≥120/70 mmHg) or an elevated home BP (≥135/85 mmHg). Overweight and obesity were defined as a body mass index of 25.0-29.9 and ≥30.0 kg/m

In Alzheimer's disease (AD), cerebral iron accumulation colocalizes with the pathological proteins amyloid-β (Aβ) and tau. Furthermore, tau-induced cortical thinning is associated with cognitive decline. In this study, quantitative susceptibility mapping (QSM) was used to investigate the whole-brain distribution pattern of cortical iron deposition and its relationships with cognition and cortical thickness in AD.This cross-sectional study prospectively recruited 30 participants with AD and 26 age- and sex-matched healthy controls (HCs). All participants underwent QSM and TWhole-brain QSM cross-sectional analysis in the AD group demonstrated widespread increased susceptibility across the cortical ribbon, asymmetrically covering the left hemisphere cerebral cortex, caudate nucleus, putamen, and partial cerebellar cortex. Whole-brain QSM regression analyses in the AD group showed that increased susceptibility covaried with lower MMSE and MoCA scores, and was predominantly located in the right parietal cortex and lateral occipital cortex. In the AD group, cortical thickness was reduced in the left superior temporal gyrus, right frontal pole, fusiform gyus, and pars opercularis, and there were increases in susceptibility in the right frontal pole (AD: mean ± SD 0.034±0.007 ppm, 95% CI: 0.032-0.037 ppm; HC: 0.030±0.005 ppm, 95% CI: 0.028-0.032 ppm; P=0.016) and pars opercularis (AD: 0.020±0.003 ppm, 95% CI: 0.018-0.021 ppm; HC: 0.017±0.002 ppm, 95% CI: 0.017-0.018 ppm; P=0.002). Susceptibility was negatively correlated with cortical thickness in the right pars opercularis in the entire cohort (r=-0.521, P0.001) and AD group (r=-0.510, P=0.005).Widespread cortical iron, as measured by QSM, accumulated in AD and iron deposition was associated with poor cognitive performance. Increased iron content was also associated with brain atrophy. Our study suggests QSM may be a useful imaging biomarker for monitoring the neurodegenerative progression of AD.

The successful diagnosis of dermatomycosis depends on specimen collection. Dermatomycosis is sampled mainly for scales, but there is a lack of research on specimens of blister fluid.To explore whether blister fluid can diagnose dermatomycosis and compare blister fluid and scale specimens for dermatomycosis diagnosis.From April to July 2021, we prospectively gathered 34 patients who needed to meet all inclusion criteria simultaneously and collected their blister fluid and scales as specimens. The two samples were tested by fluorescent stain microscopy, fungal culture and PCR, and the diagnosis results were compared.The blister fluid sample's sensitivity, specificity and accuracy were 90%, 100% and 94.1%, respectively, whereas the scales sample were 60%, 100% and 76.5%, respectively. The positive likelihood ratios were10 for both blister fluid and scales specimen, and the negative likelihood ratios were not0.1. On the Youden's index, the blister fluid specimen was 90%, and the scales specimen was 60%. As for the diagnostic odds ratio, both of them were1. By fungal culture, we detected 14 cases of fungi in blister fluid and eight in scales. On PCR, 22 cases of fungi in blister fluid and ten in scales were identified.This study demonstrated that a sample of blister fluid had better sensitivity, accuracy and Youden's index in diagnosing dermatomycosis with blister fluid. Collection of blister fluid might compensate for the inadequacy of collecting only scales specimens for mycological testing.

Plum (Prunus spp.) is an economically and nutritionally important stone fruit that is grown worldwide. Gummosis disease (GD) is one of the most common limiting factors that adversely affects the yield and quality of stone fruits such as plum. Elucidating plum fruit metabolomics responses is essential to develop sustainable agricultural practices to combat GD in the future. Herein, an ultra-high-performance liquid chromatography coupled to mass-spectrometry (UHPLC-MS) pseudo-targeted metabolomic profiling was first performed to elucidate the overall metabolic alterations in Asian plum (Prunus salicina Lindl.) fruit in response to GD. The most pivotal differential metabolites, including certain amino acids and proanthocyanidins, in GD and control groups were identified by combining multivariate data analysis with strict statistical criteria. Metabolic pathway enrichment analysis showed that GD induced a series of coordinated defence responses and reprogramming of various metabolic pathways, including glucosinolate biosynthesis, 2-oxocarboxylic acid metabolism, valine, leucine and isoleucine degradation, and isoquinoline alkaloid biosynthesis pathways. Using UHPLC-MS-based pseudo-targeted metabolomic profiling, we systematically evaluated overall metabolic modifications in Asian plum fruits in response to GD for the first time. The identified metabolic pathway alterations helped to better understand the internal relationships and related metabolic networks.

A 52-year-old woman was injured in an accident, emergency tests showed rib fracture and pleural effusion. However, lung incarceration was found during thoracic exploration which was not detected in preoperative imaging findings. Although rare, Clinicians should be careful of this possible pitfall, which may bring about poor prognosis after rib fracture.