MovePort: Multimodal Dataset of EMG, IMU, MoCap and Insole Pressure for Analyzing Abnormal Movements and Postures in Rehabilitation Training.

In most real world rehabilitation training, patients are trained to regain motion capabilities with the aid of functional/epidural electrical stimulation (FES/EES), under the support of gravity-assist systems to prevent falls. However, the lack of motion analysis dataset designed specifically for rehabilitation-related applications largely limits the conduct of pilot research. We provide an open access dataset, consisting of multimodal data collected via 16 electromyography (EMG) sensors, 6 inertial measurement unit (IMU) sensors, and 230 insole pressure sensors (IPS) per foot, together with a 26-sensor motion capture system, under different MOVEments and POstures for Rehabilitation Training (MovePort). Data were collected under diverse experimental paradigms. Twenty four participants first imitated multiple normal and abnormal body postures including (1) normal standing still, (2) leaning forward, (3) leaning back, and (4) half-squat, which in practical applications, can be detected as feedback to tune the parameters of FES/EES and gravity-assist systems to keep patients in a target body posture. Data under imitated abnormal gaits, e.g., (1) with legs raised higher under excessive electrical stimulation, and (2) with dragging legs under insufficient stimulation, were also collected. Data under normal gaits with low, medium and high speeds are also included. Pathological gait data from a subject with spastic paraplegia further increases the clinical value of our dataset. We also provide source codes to perform both intra- and inter-participant motion analyses of our dataset. We expect our dataset can provide a unique platform to promote collaboration among neurorehabilitation engineers.

Human-induced pluripotent stem cell-derived hepatocyte platform in modeling of SARS-CoV-2 infection.

Background and Aim: Currently, SARS-CoV-2 is still spreading rapidly and globally. A large proportion of patients with COVID-19 developed liver injuries. The human-induced pluripotent stem cell (iPSC)-derived hepatocytes recapitulate primary human hepatocytes and have been widely used in studies of liver diseases. Methods: To explore the susceptibility of hepatocytes to SARS-CoV-2, we differentiated iPSCs to functional hepatocytes and tried infecting them with different MOI (1, 0.1, 0.01) of SARS-CoV-2. Results: The iPSC-derived hepatocytes are highly susceptible to virus infection, even at 0.01 MOI. Other than the ancestral strain, iHeps also support the replication of SARS-CoV-2 variants including alpha, beta, theta, and delta. More interestingly, the ACE2 expression significantly upregulated after infection, suggesting a vicious cycle between virus infection and liver injury. Conclusions: The iPSC-derived hepatocytes can support the replication of SARS-CoV-2, and this platform could be used to investigate the SARS-CoV-2 hepatotropism and hepatic pathogenic mechanisms.

Exposure to polystyrene nanoplastics induces hepatotoxicity involving NRF2-NLRP3 signaling pathway in mice.

Nanoplastic contamination has been of intense concern by virtue of the potential threat to human and ecosystem health. Animal experiments have indicated that exposure to nanoplastics (NPs) can deposit in the liver and contribute to hepatic injury. To explore the mechanisms of hepatotoxicity induced by polystyrene-NPs (PS-NPs), mice and AML-12 hepatocytes were exposed to different dosages of 20 nm PS-NPs in this study. The results illustrated that in vitro and in vivo exposure to PS-NPs triggered excessive production of reactive oxygen species and repressed nuclear factor erythroid-derived 2-like 2 (NRF2) antioxidant pathway and its downstream antioxidase expression, thus leading to hepatic oxidative stress. Moreover, PS-NPs elevated the levels of NLRP3, IL-1ß and caspase-1 expression, along with an activation of NF-κB, suggesting that PS-NPs induced hepatocellular inflammatory injury. Nevertheless, the activaton of NRF2 signaling by tert-butylhydroquinone mitigated PS-NPs-caused oxidative stress and inflammation, and inbihited NLRP3 and caspase-1 expression. Conversely, the rescuing effect of NRF2 signal activation was dramatically supressed by treatment with NRF2 inhibitor brusatol. In summary, our results demonstrated that NRF2-NLRP3 pathway is involved in PS-NPs-aroused hepatotoxicity, and the activation of NRF2 signaling can protect against PS-NPs-evoked liver injury. These results provide novel insights into the hepatotoxicity elicited by NPs exposure.

Environmental pollutants and male infertility: Effects on CatSper.

Infertility is a growing health concern among many couples worldwide. Men account for half of infertility cases. CatSper, a sperm-specific Ca2+ channel, is expressed on the cell membrane of mammalian sperm. CatSper plays an important role in male fertility because it facilitates the entry of Ca2+ necessary for the rapid change in sperm motility, thereby allowing it to navigate the hurdles of the female reproductive tract and successfully locate the egg. Many pollutants present in the environment have been shown to affect the functions of CatSper and sperm, which is a matter of capital importance to understanding and solving male infertility issues. Environmental pollutants can act as partial agonists or inhibitors of CatSper or exhibit a synergistic effect. In this article, we briefly describe the structure, functions, and regulatory mechanisms of CatSper, and discuss the body of literature covering the effects of environmental pollutants on CatSper.

Comprehensive comparison of two models evaluating eco-environmental quality in Fangshan.

It is crucial to employ scientifically sound models for assessing the quality of the ecological environment and revealing the strengths and weaknesses of ecosystems. This process is vital for identifying regional ecological and environmental issues and devising relevant protective measures. Among the widely acknowledged models for evaluating ecological quality, the ecological index (EI) and remote sensing ecological index (RSEI) stand out; however, there is a notable gap in the literature discussing their differences, characteristics, and reasons for selecting either model. In this study, we focused on Fangshan District, Beijing, China, to examine the differences between the two models from 2017 to 2021. We summarized the variations in evaluation indices, importance, quantitative methods, and data acquisition times, proposing application scenarios for both models. The results indicate that the ecological environment quality in Fangshan District, Beijing, remained favorable from 2017 to 2021. There was a discernible trend of initially declining quality followed by subsequent improvement. The variation in the calculation results is evident in the overall correlation between the RSEI and EI. Particularly noteworthy is the significantly smaller correlation between EI and the RSEI in 2021 than in the other two years. This discrepancy is attributed to shifts in the contribution of the evaluation indices within the RSEI model. The use of diverse quantitative methods for evaluating indicators has resulted in several variations. Notably, the evaluation outcomes of the EI model exhibit a stronger correlation with land cover types. This correlation contributes to a more pronounced fluctuation in RSEI levels from 2017 to 2021, with the EI model's evaluation results in 2019 notably surpassing those of the RSEI model. Ultimately, the most prominent disparities lie in the calculation results for water areas and construction land. The substantial difference in water areas is attributed to the distinct importance assigned to evaluation indicators between the two models. Moreover, the notable difference in construction land arises from the use of different quantification methods for evaluation indicators. In general, the EI model has suggested to be more comprehensive and effectively captures the annual comprehensive status of the ecological environment and the multiyear change characteristics of the administrative region. On the other hand, RSEI models exhibit greater flexibility and ease of implementation, independent of spatial and temporal scales. These findings contribute to a clearer understanding of the models' advantages and limitations, offering guidance for decision makers and valuable insights for the improvement and development of ecological environmental quality evaluation models.

A Robust and Real-Time Framework of Cross-Subject Myoelectric Control Model Calibration via Multi-Source Domain Adaptation.

Surface electromyogram (sEMG) has been widely used in hand gesture recognition. However, most previous studies focused on user-personalized models, which require a great amount of data from each new target user to learn the user-specific EMG patterns. In this work, we present a novel real-time gesture recognition framework based on multi-source domain adaptation, which learns extra knowledge from the data of other users, thereby reducing the data collection burdens on the target user. Additionally, compared with conventional domain adaptation methods which treat data from all users in the source domain as a whole, the proposed multi-source method treat data from different users as multiple separate source domains. Therefore, more detailed statistical information on the data distribution from each user can be learned effectively. High-density sEMG (256 channels) from 20 subjects was used to validate the proposed method. Importantly, we evaluated our method with a simulated real-time processing pipeline on continuous sEMG data stream, rather than well-segmented data. The false alarm rate during rest periods in an EMG data stream, which is typically neglected by previous studies performing offline analyses, was also considered. Our results showed that, with only 1 s sEMG data per gesture from the new user, the 10-gesture classification accuracy reached 87.66 % but the false alarm rate was reduced to 1.95 %. Our method can reduce the frustratingly heavy data collection burdens on each new user.

Co-exposure to polystyrene nanoplastics and triclosan induces synergistic cytotoxicity in human KGN granulosa cells by promoting reactive oxygen species accumulation.

In recent years, nanoplastics (NPs) and triclosan (TCS, a pharmaceutical and personal care product) have emerged as environmental pollution issues, and their combined presence has raised widespread concern regarding potential risks to organisms. However, the combined toxicity and mechanisms of NPs and TCS remain unclear. In this study, we investigated the toxic effects of polystyrene NPs and TCS and their mechanisms on KGN cells, a human ovarian granulosa cell line. We exposed KGN cells to NPs (150 µg/mL) and TCS (15 µM) alone or together for 24 hours. Co-exposure significantly reduced cell viability. Compared with exposure to NPs or TCS alone, co-exposure increased reactive oxygen species (ROS) production. Interestingly, co-exposure to NPs and TCS produced synergistic effects. We examined the activity of superoxide dismutase (SOD) and catalase (CAT), two antioxidant enzymes; it was significantly decreased after co-exposure. We also noted an increase in the lipid oxidation product malondialdehyde (MDA) after co-exposure. Furthermore, co-exposure to NPs and TCS had a more detrimental effect on mitochondrial function than the individual treatments. Co-exposure activated the NRF2-KEAP1-HO-1 antioxidant stress pathway. Surprisingly, the expression of SESTRIN2, an antioxidant protein, was inhibited by co-exposure treatments. Co-exposure to NPs and TCS significantly increased the autophagy-related proteins LC3B-II and LC3B-Ⅰ and decreased P62. Moreover, co-exposure enhanced CASPASE-3 expression and inhibited the BCL-2/BAX ratio. In summary, our study revealed the synergistic toxic effects of NPs and TCS in vitro exposure. Our findings provide insight into the toxic mechanisms associated with co-exposure to NPs and TCS to KGN cells by inducing oxidative stress, activations of the NRF2-KEAP1-HO-1 pathway, autophagy, and apoptosis.

Evaluation of the clinical utility of extended non-invasive prenatal testing in the detection of chromosomal aneuploidy and microdeletion/microduplication.

BACKGROUND: With the development of whole-genome sequencing technology, non-invasive prenatal testing (NIPT) has been applied gradually to screen chromosomal microdeletions and microduplications that cannot be detected by traditional karyotyping. However, in NIPT, some false positives and false negatives occur. This study aimed to investigate the applicability of extended NIPT (NIPT-PLUS) in the detection of chromosomal aneuploidy and microdeletion/microduplication syndrome (MMS). METHODS: A total of 452 pregnancies that underwent prenatal diagnostic testing (amniocentesis or chorionic villus sampling) by chromosomal microarray analysis (CMA), were screened by NIPT-PLUS from the peripheral blood sample of the pregnant women. The results of the two tested items were compared and analysed. RESULTS: Of the 452 cases, 335 (74.12%) had positive CMA results, and 117 (25.88%) had no abnormal results. A total of 86 cases of trisomy 21, 18 and 13 and sex chromosome aneuploidy (SCA) were detected by CMA and NIPT-PLUS, with a detection rate of 96.51% (83/86). Among them, the detection rates of T18, T13; 47, XXY; 47, XXX and 47 XYY were 100%, and the detection rates of T21 and 45 XO were 96.55% and 90%, respectively. The detection sensitivity of rare chromosomal trisomy (RAT) was 80% (4/5). The positive predictive values of NIPT-PLUS for chromosome aneuploidy T21, T18 and T13 and for SCA and RAT were 90.32%, 87.50%, 25.00%, 88.89% and 50%, respectively. A total of 249 cases (74.32%) of chromosomal MMS were detected by CMA. The detection rate of NIPT-PLUS was 63.86% (159/249), and 90 cases (36.14%) were missed. The larger the MMS fragment, the higher the NIPT-PLUS detection sensitivity. In addition, most small fragments were of maternal origin. CONCLUSION: The comparison between the CMA and NIPT-PLUS techniques shows that NIPT-PLUS has high sensitivity for detecting chromosomal aneuploidy and chromosomal copy number variations (CNVs) with fragments > 5 M. However, the sensitivity of CNV for fragments < 5 M is low, and the missed detection rate is high. Additionally, confined placental mosaicism and foetal mosaicism are the key factors causing false negatives in NIPT-PLUS, while maternal chromosomal abnormalities and confined placental mosaicism are key contributors to false positives, so appropriate genetic counselling is especially important for pregnant women before and after NIPT-PLUS testing.

[Positive effects of Xuebijing injection on intestinal microbiota and metabolite spectrum in septic rats].

OBJECTIVE: To explore the effect of Xuebijing injection on inflammation in sepsis by regulating intestinal microbiota and its metabolites. METHODS: A total of 45 male Sprague-Dawley (SD) rats were randomly divided into Sham operation group (Sham group), cecal ligation and perforation (CLP) induced sepsis group (CLP group), and Xuebijing intervention group (XBJ group, 4 mL/kg Xuebijing injection was injected intraperitoneally at 1 hour after CLP), with 15 rats in each group. The survival of rats was observed at 24 hours after operation and sacrificed. Feces were collected for 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) analysis. RESULTS: At 24 hours after operation, all rats in the Sham group survived, the mortality of rats in the XBJ group was lower than that in the CLP group [47% (7/15) vs. 60% (9/15), P > 0.05]. Compared with the Sham group, the diversity of gut microbiota in the CLP group decreased, the dominant flora changed, and the abundance of inflammation-related flora increased. Xuebijing improved the changes in gut microbiota caused by sepsis, and α diversity showed an increasing trend (Ace index: 406.0±22.5 vs. 363.2±38.2, Chao1 index: 409.7±21.8 vs. 362.4±42.5, both P > 0.05). Restrictive constrained principal coordinate analysis (cPCoA) showed a high similarity in gut microbiota among the same group of rats. The CLP group was dominated by Bacteroidetes, while the Sham and XBJ groups were dominated by Firmicutes. In addition, compared with the CLP group, Xuebijing treatment increased the abundance of beneficial bacteria in septic rats, such as Verrucomicrobia, Akkermansia and Lactobacillus. LC-MS and orthogonal partial least squares discriminant analysis (OPLS-DA) showed that there were 12 main differential metabolites among the three groups, and there were certain correlations between these metabolites, which were related to amino acid and lipid metabolism. Correlation analysis showed a significant correlation between changes in metabolites and microbial communities. CONCLUSIONS: Xuebijing can improve the survival rate of septic rats, regulate the composition of intestinal flora and related metabolites, which provides a new pathophysiological mechanism for Xuebijing in the treatment of sepsis.

VPT-like genes modulate Rhizobium-legume symbiosis and phosphorus adaptation.

Although vacuolar phosphate transporters (VPTs) are essential for plant phosphorus adaptation, their role in Rhizobium-legume symbiosis is unclear. In this study, homologous genes of VPT1 (MtVPTs) were identified in Medicago truncatula to assess their roles in Rhizobium-legume symbiosis and phosphorus adaptation. MtVPT2 and MtVPT3 mainly positively responded to low and high phosphate, respectively. However, both mtvpt2 and mtvpt3 mutants displayed shoot phenotypes with high phosphate sensitivity and low phosphate tolerance. The root-to-shoot phosphate transfer efficiency was significantly enhanced in mtvpt3 but weakened in mtvpt2, accompanied by lower and higher root cytosolic inorganic phosphate (Pi) concentration, respectively. Low phosphate induced MtVPT2 and MtVPT3 expressions in nodules. MtVPT2 and MtVPT3 mutations markedly reduced the nodule number and nitrogenase activity under different phosphate conditions. Cytosolic Pi concentration in nodules was significantly lower in mtvpt2 and mtvpt3 than in the wildtype, especially in tissues near the base of nodules, probably due to inhibition of long-distance Pi transport and cytosolic Pi supply. Also, mtvpt2 and mtvpt3 could not maintain a stable cytosolic Pi level in the nodule fixation zone as the wildtype under low phosphate stress. These findings show that MtVPT2 and MtVPT3 modulate phosphorus adaptation and rhizobia-legume symbiosis, possibly by regulating long-distance Pi transport.

Transcriptional repression of MdMa1 by MdMYB21 in Ma locus decreases malic acid content in apple fruit.

Malic acid is a major organic acid component of apples and a crucial determinant of fruit organoleptic quality. A candidate gene for malic acid content, designated MdMa1, was previously identified in the Ma locus, which is a major quantitative trait locus (QTL) for apple fruit acidity located on the linkage group 16. Region-based association mapping to detect candidate genes in the Ma locus identified MdMa1 and an additional MdMYB21 gene putatively associated with malic acid. MdMYB21 was significantly associated with fruit malic acid content, accounting for ~7.48% of the observed phenotypic variation in the apple germplasm collection. Analyses of transgenic apple calli, fruits and tomatoes demonstrated that MdMYB21 negatively regulated malic acid accumulation. The apple fruit acidity-related MdMa1 and its tomato ortholog, SlALMT9, exhibited lower expression profiles in apple calli, mature fruits and tomatoes in which MdMYB21 was overexpressed, compared with their corresponding wild-type variety. MdMYB21 directly binds to the MdMa1 promoter and represses its expression. Interestingly, a 2-bp variation in the MdMYB21 promoter region altered its expression and regulation of its target gene, MdMa1, expression. Our findings not only demonstrate the efficiency of integrating QTL and association mapping in the identification of candidate genes controlling complex traits in apples, but also provide insights into the complex regulatory mechanism of fruit malic acid accumulation.

Pharmacogenomics of oxcarbazepine in the treatment of epilepsy.

Oxcarbazepine (OXC) is one of the preferred drugs for partial seizures and generalized tonic-clonic seizures. However, clinical studies have found that there are considerable differences among different populations in OXC therapeutic efficacy or safety that result from the function changes of metabolic enzymes, transporters and other receptors involved in pharmacokinetics and pharmacodynamics in vivo. The authors collected all the information on the clinically reported associations between variants of common genes (e.g., UGT1A9, HLA-B, ABCB1) and OXC. In conclusion, these associations based on variants are beneficial for adjusting the medication regimen, which could be useful for individualized treatment with OXC.

As a new-generation aromatic antiepileptic drug, oxcarbazepine (OXC) is often used for epilepsy treatment. It is known that when OXC is absorbed, it is reduced to an active metabolite in the liver and enters the brain through the blood circulation to play an antiepileptic role. Therefore, the variations of proteins participating in the process, including drug metabolic enzymes, transporters, drug targets and other receptors, have an effect on the efficacy and safety of OXC in vivo. In this study, the associations of some variants of common genes with OXC are summarized to provide epileptic patients an appropriate dose of OXC or reduce the risk of OXC-induced toxicity, which are in favor of personalized OXC treatment for patients with epilepsy.

Oral exposure to polystyrene nanoplastics reduced male fertility and even caused male infertility by inducing testicular and sperm toxicities in mice.

Nanoplastics (NPs) are the novel hazardous materials and ubiquitous in environment with different sizes. Although recent studies showed testicular toxicity of PS-NPs, whether and how NPs affect male fertility and whether they have the size-dependent effect remain ambiguous in mammals. In this study, the male mice were orally exposed to 25-, 50-, and 100-nm polystyrene NPs (PS-NPs) for 56 days. All three sized PS-NPs reduced male fertility and even caused male infertility. They accumulated in the testes, induced oxidative stress, affected the expression of apoptosis- and inflammation-related genes, and compromised energy metabolism, resulting in damaged testicular microstructure and functions. PS-NPs caused more severe testicular toxicity in infertile mice than in fertile mice. In addition, PS-NPs inhibited sperm capacitation and capacitation-dependent processes in infertile mice but not in fertile mice. In infertile mice, PS-NPs reduced the sperm levels of two Rho GTPases (RAC1 and CDC42) via increasing their ubiquitination levels and diminished sperm filamentous actin polymerization, thus inhibiting sperm capacitation. However, these testicular and sperm toxicities showed no size-dependent effect among three sized PS-NPs. In conclusion, PS-NPs inhibit male fertility by their multifaceted toxicity on testes and sperm in mice, providing novel insights into reproductive risks of NPs to mammals.

GBC: a parallel toolkit based on highly addressable byte-encoding blocks for extremely large-scale genotypes of species.

Whole -genome sequencing projects of millions of subjects contain enormous genotypes, entailing a huge memory burden and time for computation. Here, we present GBC, a toolkit for rapidly compressing large-scale genotypes into highly addressable byte-encoding blocks under an optimized parallel framework. We demonstrate that GBC is up to 1000 times faster than state-of-the-art methods to access and manage compressed large-scale genotypes while maintaining a competitive compression ratio. We also showed that conventional analysis would be substantially sped up if built on GBC to access genotypes of a large population. GBC's data structure and algorithms are valuable for accelerating large-scale genomic research.

[Efficacy and safety of sivelestat sodium in patients with sepsis].

OBJECTIVE: To investigate the efficacy and safety of sivelestat sodium in patients with sepsis. METHODS: The clinical data of 141 adult patients with sepsis admitted to the intensive care unit (ICU) of the First Affiliated Hospital of Zhengzhou University from January 1, 2019 to January 1, 2022 were retrospectively analyzed. The patients were divided into the sivelestat sodium group (n = 70) and the control group (n = 71) according to whether they received sivelestat sodium or not. The efficacy indexes included oxygenation index, procalcitonin (PCT), C-reactive protein (CRP), white blood count (WBC), sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II (APACHE II) before and after 7 days of treatment, as well as ventilator supporting time, the length of ICU stay, the length of hospital stay and ICU mortality. The safety indicators included platelet count (PLT) and liver and kidney function. RESULTS: There were no significant differences in age, gender, underlying diseases, infection site, basic drugs, etiology, oxygenation index, biochemical indexes, SOFA and APACHE II scores between the two groups. Compared with the control group, the oxygenation index in 7 days was significantly increased [mmHg (1 mmHg ≈ 0.133 kPa): 233.5 (181.0, 278.0) vs. 202.0 (153.0, 243.0), P < 0.01], the levels of PCT, CRP, alanine aminotransferase (ALT) and APACHE II score were significantly decreased in the sivelestat sodium group [PCT (µg/L): 0.87 (0.41, 1.61) vs. 1.53 (0.56, 5.33), CRP (mg/L): 64.12 (19.61, 150.86) vs. 107.20 (50.30, 173.00), ALT (U/L): 25.0 (15.0, 43.0) vs. 31.0 (20.0, 65.0), APACHE II: 14 (11, 18) vs. 16 (13, 21), all P < 0.05]. However, there were no significant differences in SOFA, WBC, serum creatinine (SCr), PLT, total bilirubin (TBil), aspartate aminotransferase (AST) in 7 days between the sivelestat sodium group and the control group [SOFA: 6.5 (5.0, 10.0) vs. 7.0 (5.0, 10.0), WBC (×109/L): 10.5 (8.2, 14.7) vs. 10.5 (7.2, 15.2), SCr (µmol/L): 76.0 (50.0, 124.1) vs. 84.0 (59.0, 129.0), PLT (×109/L): 127.5 (59.8, 212.3) vs. 121.0 (55.0, 211.0), TBil (µmol/L): 16.8 (10.0, 32.1) vs. 16.6 (8.4, 26.9), AST (U/L): 31.5 (22.0, 62.3) vs. 37.0 (24.0, 63.0), all P > 0.05]. The ventilator supporting time and the length of ICU stay in the sivelestat sodium group were significantly shorter than those in control group [ventilator supporting time (hours): 147.50 (86.83, 220.00) vs. 182.00 (100.00, 360.00), the length of ICU stay (days): 12.5 (9.0, 18.3) vs. 16.0 (11.0, 23.0), both P < 0.05]. However, there were no significant differences in the length of hospital stay and ICU mortality between the sivelestat sodium group and the control group [the length of hospital stay (days): 20.0 (11.0, 27.3) vs. 13.0 (11.0, 21.0), ICU mortality: 17.1% (12/70) vs. 14.1% (10/71), both P > 0.05]. CONCLUSIONS: Sivelestat sodium is safe and effective in patients with sepsis. It can improve the oxygenation index and APACHE II score, reduce the levels of PCT and CRP, shorten ventilator supporting time and the length of ICU stay. No adverse reactions such as liver and kidney function injury and platelet abnormality are observed.

Correlation Between Plasma NLRP3, IL-1ß, and IL-18 and Diabetic Nephropathy in Patients With Type 2 Diabetes.

Context: Diabetic nephropathy (DN) is a common microvascular complication in diabetic patients. The pathogenesis of DN is complex. Inflammatory response may play a key role as a common downstream pathway. Objective: The study intended to explore the relationship between the levels of plasma nucleotide-binding oligomeric domain-like receptor protein 3 (NLRP3 inflammasome), interleukin-1ß (IL-1ß), and IL-18 and the progression of type 2 diabetic nephropathy to clarify their relationship with type 2 diabetes mellitus (T2DM) and to provide evidence for clinical treatment. Design: The research team performed a controlled observational study. Setting: The study took place at Baoding No. 1 Central Hospital in Baoding, Hebei, China. Participants: Participants were 153 patients with T2DM who received treatment at the hospital between October 2020 and October 2021. The research team allocated 30 participants without evidence of DN to the control group. Based on the DN stage, the team assigned the 123 remaining participants to one of five observation groups: (1) 32 participants with stage 1 DN to the DN1 group, (2) 31 participants with stage 2 DN to the DN2 group, (3) 30 participants with stage 3 DN to the DN3 group, (4) 30 participants with stage 4 DN to the DN4 group, and (5) 29 participants with stage 5 DN to the DN5 group. Outcome Measures: The research team measured participants' levels of "nucleotide binding oligomeric domain-like receptor protein 3" (NLRP3), interleukin-1 beta (IL-1ß), and IL-18 and used the Spearman rank correlation analysis to determine the correlation between those levels and the DN stages. Results: The levels of NLRP3 , IL-1ß and IL-18 in all the five observation groups were significantly higher than those in the control group (all P < .01). The levels were also significantly higher: (1) in the DN2, DN3, DN4, and DN5 groups than those in the DN1 group (all P < .01); (2) in the DN3, DN4, and DN5 groups than those in the DN2 group (all P < .01); (3) in the DN4 and DN5 groups than those in the DN3 group (all P < .01); and (4) in the DN5 groups than those in the DN4 group (all P < .01). The Spearman rank correlation analysis showed that the NLRP3, IL-1ß, and IL-18 levels were significantly positively correlated with the DN stage (P = .01). Conclusions: NLRP3, IL-1ß and IL-18 played an important role in the progression of T2DM, and their levels increased with the aggravation of DN. Therefore, the plasma levels of NLRP3, IL-1ß and IL-18 can be useful as indicators of the occurrence and development of DN and can provide clinical guidance for the early diagnosis of DN and for the determination and adjustment of treatment plans.

Exposure to nanoplastics induces mitochondrial impairment and cytomembrane destruction in Leydig cells.

Plastic particle pollution poses an emerging threat to ecological and human health. Laboratory animal studies have illustrated that nano-sized plastics can accumulate in the testis and cause testosterone deficiency and spermatogenic impairment. In this study, TM3 mouse Leydig cells were in vitro exposed to polystyrene nanoparticles (PS-NPs, size 20 nm) at dosages of 50, 100 and 150 µg/mL to investigate their cytotoxicity. Our results demonstrated that PS-NPs can be internalized into TM3 Leydig cells and led to a concentration-dependent decline in cell viability. Furthermore, PS-NPs stimulation amplified ROS generation and initiated cellular oxidative stress and apoptosis. Moreover, PS-NPs treatment affected the mitochondrial DNA copy number and collapsed the mitochondrial membrane potential, accompanied by a disrupted energy metabolism. The cells exposed to PS-NPs also displayed a down-regulated expression of steroidogenesis-related genes StAR, P450scc and 17ß-HSD, along with a decrease in testosterone secretion. In addition, treatment with PS-NPs destructed plasma membrane integrity, as presented by increase in lactate dehydrogenase release and depolarization of cell membrane potential. In summary, these data indicated that exposure to PS-NPs in vitro produced cytotoxic effect on Leydig cells by inducing oxidative injury, mitochondrial impairment, apoptosis, and cytomembrane destruction. Our results provide new insights into male reproductive toxicity caused by NPs.

Toxic effects of per- and polyfluoroalkyl substances on sperm: Epidemiological and experimental evidence.

As emerging organic contaminants, per- and polyfluoroalkyl substances (PFASs) have aroused worldwide concern due to their environmental persistence, ubiquitous presence, bioaccumulation, and potential toxicity. It has been demonstrated that PFASs can accumulate in human body and cause multiple adverse health outcomes. Notably, PFASs have been detected in the semen of human, posing a potential hazard to male fecundity. This article reviews the evidence about the toxic effects of exposure to PFASs on male reproduction, focusing on the sperm quality. Epidemiological studies showed that PFASs, such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), were adversely associated with the semen parameters in humans, including sperm count, morphology and motility. Experimental results also confirmed that PFAS exposure led to testicular and epididymal damage, therefore impairing spermatogenesis and sperm quality. The mechanisms of reproductive toxicity of PFASs may be involved in blood-testosterone barrier destruction, testicular apoptosis, testosterone synthesis disorder, and membrane lipid composition alteration, oxidative stress and Ca2+ influx in sperm. In conclusion, this review highlighted the potential threat of exposure to PFASs to human spermatozoa.

Allelic variation of MdMYB123 controls malic acid content by regulating MdMa1 and MdMa11 expression in apple.

Acidity is a key determinant of fruit organoleptic quality. Here, a candidate gene for fruit acidity, designated MdMYB123, was identified from a comparative transcriptome study of two Ma1Ma1 apple (Malus domestica) varieties, "Qinguan (QG)" and "Honeycrisp (HC)" with different malic acid content. Sequence analysis identified an A→T SNP, which was located in the last exon, resulting in a truncating mutation, designated mdmyb123. This SNP was significantly associated with fruit malic acid content, accounting for 9.5% of the observed phenotypic variation in apple germplasm. Differential MdMYB123- and mdmyb123-mediated regulation of malic acid accumulation was observed in transgenic apple calli, fruits, and plantlets. Two genes, MdMa1 and MdMa11, were up- and down-regulated in transgenic apple plantlets overexpressing MdMYB123 and mdmyb123, respectively. MdMYB123 could directly bind to the promoter of MdMa1 and MdMa11, and induce their expression. In contrast, mdmyb123 could directly bind to the promoters of MdMa1 and MdMa11, but with no transcriptional activation of both genes. In addition, gene expression analysis in 20 different apple genotypes based on SNP locus from "QG" × "HC" hybrid population confirmed a correlation between A/T SNP with expression levels of MdMa1 and MdMa11. Our finding provides valuable functional validation of MdMYB123 and its role in the transcriptional regulation of both MdMa1 and MdMa11, and apple fruit malic acid accumulation.