Nanoreactors with Cascade Catalytic Activity Reprogram the Tumor Microenvironment for Enhanced Immunotherapy by Synchronously Regulating Treg and Macrophage Cells.

Immunotherapy has been extensively utilized and studied as a prominent therapeutic strategy for tumors. However, the presence of a hypoxic immunosuppressive tumor microenvironment significantly reduces the efficacy of the treatment, thus impeding its application. In addition, the hypoxic microenvironment can also lead to the enrichment of immunosuppressive cells and reduce the effectiveness of tumor immunotherapy; nanoparticles with biocatalytic activity have the ability to relieve hypoxia in tumor tissues and deliver drugs to target cells and have been widely concerned and applied in the field of tumor therapy. The present study involved the development of a dual nanodelivery system that effectively targets the immune system to modify the tumor microenvironment (TME). The nanodelivery system was developed by incorporating R848 and Imatinib (IMT) into Pt nanozyme loaded hollow polydopamine (P@HP) nanocarriers. Subsequently, their surface was modified with specifically targeted peptides that bind to M2-like macrophages and regulatory T (Treg) cells, thereby facilitating the precise targeting of these cells. When introduced into the tumor model, the nanocarriers were able to selectively target immune cells in tumor tissue, causing M2-type macrophages to change into the M1 phenotype and reducing Treg activation within the tumor microenvironment. In addition, the carriers demonstrated exceptional biocatalytic activity, effectively converting H2O2 into oxygen and water at the tumor site while the drug was active, thereby alleviating the hypoxic inhibitory conditions present in the tumor microenvironment. Additionally, this further enhanced the infiltration of M1-type macrophages and cytotoxic T lymphocytes. Moreover, when used in conjunction with immune checkpoint therapy, the proposed approach demonstrated enhanced antitumor immunotherapeutic effects. The bimodal targeted immunotherapeutic strategy developed in the present study overcomes the drawbacks of traditional immunotherapy approaches while offering novel avenues for the treatment of cancer.

Limb circumference measurements contributing to the diagnosis of snake venom-induced compartment syndrome.

Background: The present study aimed to investigate the relationship between swollen limb circumference and compartment pressure after a snakebite and to evaluate the diagnostic value of the circumference difference between the healthy and affected sides and the circumference growth rate for snake venom-induced compartment syndrome (CS). Method: The study was based on a prospective cohort study of snakebite patients at the emergency department of West China Hospital from May 2021 to October 2022. The snakebite patients were divided into the CS and non-compartment syndrome (NCS) groups. The diagnostic value of the circumference of the swollen limb for the CS after snakebite was evaluated using a receiver-operating characteristic curve analysis, and the cut-off value of the circumference of the swollen limb for CS after snakebite was calculated with sensitivity and specificity. Result: The present study enrolled 115 patients with severely swollen limbs after snakebite. The mean age was 59.1 ± 13.6 years, with 58 (50.4 %) female cases and 57 (49.6 %) male cases. There were 33 (28.7 %) cases where the upper limbs were injured and 82 (71.3 %) cases where the lower limbs were injured. These patients were divided into CS (n = 19) and NCS (n = 96) groups. The area under the curve (AUC) for the 15 cm circumference difference and circumferential growth rate of the upper edge of the patella was 0.683 (95 % CI 0.508 to 0.858, P = 0.037), and 0.685 (95 % CI 0.512 to 0.858, P = 0.035). The optimal cut-off values for the 15 cm circumference difference and circumferential growth rate of the upper edge of the patella to distinguish CS and NCS were 2.8 cm (sensitivity = 76.9 %, specificity = 66.7 %) and 7 % (sensitivity = 76.9 %, specificity = 66.7 %), respectively. Conclusion: Limb circumference measurement is a non-invasive, convenient, effective, and repeatable bedside test that can assist clinicians in the early detection of suspected snake venom-induced CS in patients exhibiting limb swelling after snake bites.

Orally biomimetic metal-phenolic nanozyme with quadruple safeguards for intestinal homeostasis to ameliorate ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is defined by persistent inflammatory processes within the gastrointestinal tract of uncertain etiology. Current therapeutic approaches are limited in their ability to address oxidative stress, inflammation, barrier function restoration, and modulation of gut microbiota in a coordinated manner to maintain intestinal homeostasis. RESULTS: This study involves the construction of a metal-phenolic nanozyme (Cur-Fe) through a ferric ion-mediated oxidative coupling of curcumin. Cur-Fe nanozyme exhibits superoxide dismutase (SOD)-like and •OH scavenging activities, demonstrating significant anti-inflammatory and anti-oxidant properties for maintaining intracellular redox balance in vitro. Drawing inspiration from Escherichia coli Nissle 1917 (EcN), a biomimetic Cur-Fe nanozyme (CF@EM) is subsequently developed by integrating Cur-Fe into the EcN membrane (EM) to improve the in vivo targeting ability and therapeutic effectiveness of the Cur-Fe nanozyme. When orally administered, CF@EM demonstrates a strong ability to colonize the inflamed colon and restore intestinal redox balance and barrier function in DSS-induced colitis models. Importantly, CF@EM influences the gut microbiome towards a beneficial state by enhancing bacterial diversity and shifting the compositional structure toward an anti-inflammatory phenotype. Furthermore, analysis of intestinal microbial metabolites supports the notion that the therapeutic efficacy of CF@EM is closely associated with bile acid metabolism. CONCLUSION: Inspired by gut microbes, we have successfully synthesized a biomimetic Cur-Fe nanozyme with the ability to inhibit inflammation and restore intestinal homeostasis. Collectively, without appreciable systemic toxicity, this work provides an unprecedented opportunity for targeted oral nanomedicine in the treatment of ulcerative colitis.

Relationship between maternal postpartum depression, fatigue, sleep quality and infant growth: A cross-sectional study.

BACKGROUND: Current research separately analyzed the connection between postpartum depression, fatigue, sleep and infant development. However, depression, fatigue and sleep quality often coexisted as adverse symptoms in postpartum women and influenced infant development together. This study explored the maternal postpartum symptoms on infant growth. METHODS: Our study included 224 pairs of singleton full-term mothers and their infants who underwent routine pediatric outpatient clinics. Latent profile analysis was applied to identify the latent classes based on mothers' postpartum depression, fatigue and sleep profile characteristics. We evaluated the maternal adverse symptoms and infant development using multivariable logistic regressions. RESULTS: Totally, 224 pairs of eligible mothers (28.85 ± 4.43 years) and infants (30.93 ± 3.26 days) participated in this study. Latent profile analysis identified 3 latent groups: mild (58.04%), moderate (34.37%), and severe (7.59%) postpartum adverse symptoms. Postpartum adverse symptoms were associated with delayed development in the baby's motor level (χ2 = 6.572, p = .037) and weight-for-length (χ2 = 9.652, p = .008). After controlling for mother and infant related factors, postpartum adverse symptoms remained a risk factor for infant motor level (odds ratio [OR]: 4.35; 95% confidence interval [CI]: 1.25-15.08) and weight-for-length (OR: 5.53; 95% CI: 1.55-19.74). CONCLUSIONS: Maternal postpartum depression, fatigue and sleep quality are associated with infant development. Clinically, mothers with these symptoms should be intervened timely to avoid the aggravation of maternal symptoms, which affect baby's development.

A cross-temporal contrastive disentangled model for ancient Chinese understanding.

Ancient Chinese is a crucial bridge for understanding Chinese history and culture. Most existing works utilize high-resource modern Chinese to understand low-resource ancient Chinese, but they fail to fully consider the semantic and syntactic gaps between them due to their changes over time, resulting in the misunderstanding of ancient Chinese. Hence, we propose a novel language pre-training framework for ancient Chinese understanding based on the Cross-temporal Contrastive Disentanglement Model (CCDM), which bridges the gap between modern and ancient Chinese with their parallel corpus. Specifically, we first explore a cross-temporal data augmentation method by disentangling and reconstructing the parallel ancient-modern corpus. It is noteworthy that the proposed decoupling strategy takes full account of the cross-temporal character between ancient and modern Chinese. Then, cross-temporal contrastive learning is exploited to train the model by fully leveraging the cross-temporal information. Finally, the trained language model is utilized for downstream tasks. We conduct extensive experiments on six ancient Chinese understanding tasks. Results demonstrate that our model outperforms the state-of-the-art baselines. Our framework also holds potential applicability to other languages that have undergone evolutionary changes, leading to shifts in syntax and semantics.1.

Sulforaphane enhanced muscle growth by promoting lipid oxidation through modulating key signaling pathways.

Sulforaphane (SFN) has shown diverse effects on human health and diseases. SFN was administered daily to C57BL/6J mice at doses of 1 mg/kg (SFN1) and 3 mg/kg (SFN3) for 8 weeks. Both doses of SFN accelerated body weight increment. The cross-sectional area and diameter of Longissimus dorsi (LD) muscle fibers were enlarged in SFN3 group. Triglyceride (TG) and total cholesterol (TC) levels in LD muscle were decreased in SFN groups. RNA sequencing results revealed that 2455 and 2318 differentially expressed genes (DEGs) were found in SFN1 and SFN3 groups, respectively. Based on GO enrichment analysis, 754 and 911 enriched GO terms in the SFN1 and SFN3 groups, respectively. KEGG enrichment analysis shown that one KEGG pathway was enriched in the SFN1 group, while six KEGG pathways were enriched in the SFN3 group. The expressions of nine selected DEGs validated with qRT-PCR were in line with the RNA sequencing data. Furthermore, SFN treatment influenced lipid and protein metabolism related pathways including AMPK signaling, fatty acid metabolism signaling, cholesterol metabolism signalling, PPAR signaling, peroxisome signaling, TGFß signaling, and mTOR signaling. In summary, SFN elevated muscle fibers size and reduced TG and TC content of in LD muscle by modulating protein and lipid metabolism-related signaling pathways.

ResTransUnet: An effective network combined with Transformer and U-Net for liver segmentation in CT scans.

Liver segmentation is a fundamental prerequisite for the diagnosis and surgical planning of hepatocellular carcinoma. Traditionally, the liver contour is drawn manually by radiologists using a slice-by-slice method. However, this process is time-consuming and error-prone, depending on the radiologist's experience. In this paper, we propose a new end-to-end automatic liver segmentation framework, named ResTransUNet, which exploits the transformer's ability to capture global context for remote interactions and spatial relationships, as well as the excellent performance of the original U-Net architecture. The main contribution of this paper lies in proposing a novel fusion network that combines Unet and Transformer architectures. In the encoding structure, a dual-path approach is utilized, where features are extracted separately using both convolutional neural networks (CNNs) and Transformer networks. Additionally, an effective feature enhancement unit is designed to transfer the global features extracted by the Transformer network to the CNN for feature enhancement. This model aims to address the drawbacks of traditional Unet-based methods, such as feature loss during encoding and poor capture of global features. Moreover, it avoids the disadvantages of pure Transformer models, which suffer from large parameter sizes and high computational complexity. The experimental results on the LiTS2017 dataset demonstrate remarkable performance for our proposed model, with Dice coefficients, volumetric overlap error (VOE), and relative volume difference (RVD) values for liver segmentation reaching 0.9535, 0.0804, and -0.0007, respectively. Furthermore, to further validate the model's generalization capability, we conducted tests on the 3Dircadb, Chaos, and Sliver07 datasets. The experimental results demonstrate that the proposed method outperforms other closely related models with higher liver segmentation accuracy. In addition, significant improvements can be achieved by applying our method when handling liver segmentation with small and discontinuous liver regions, as well as blurred liver boundaries. The code is available at the website: https://github.com/Jouiry/ResTransUNet.

Inhibiting proBDNF to mature BDNF conversion leads to ASD-like phenotypes in vivo.

Autism Spectrum Disorders (ASD) comprise a range of early age-onset neurodevelopment disorders with genetic heterogeneity. Most ASD related genes are involved in synaptic function, which is regulated by mature brain-derived neurotrophic factor (mBDNF) and its precursor proBDNF in a diametrically opposite manner: proBDNF inhibits while mBDNF potentiates synapses. Here we generated a knock-in mouse line (BDNFmet/leu) in which the conversion of proBDNF to mBDNF is attenuated. Biochemical experiments revealed residual mBDNF but excessive proBDNF in the brain. Similar to other ASD mouse models, the BDNFmet/leu mice showed reduced dendritic arborization, altered spines, and impaired synaptic transmission and plasticity in the hippocampus. They also exhibited ASD-like phenotypes, including stereotypical behaviors and deficits in social interaction. Moreover, the plasma proBDNF/mBDNF ratio was significantly increased in ASD patients compared to normal children in a case-control study. Thus, deficits in proBDNF to mBDNF conversion in the brain may contribute to ASD-like behaviors, and plasma proBDNF/mBDNF ratio may be a potential biomarker for ASD.

Recent advances and challenges in the interaction between myofibrillar proteins and flavor substances.

Myofibrillar proteins are an important component of proteins. Flavor characteristics are the key attributes of food quality. The ability of proteins to bind flavor is one of their most fundamental functional properties. The dynamic balance of release and retention of volatile flavor compounds in protein-containing systems largely affects the sensory quality and consumer acceptability of foods. At present, research on flavor mainly focuses on the formation mechanism of flavor components, while there are few reports on the release and perception of flavor components. This review introduces the composition and structure of myofibrillar proteins, the classification of flavor substances, the physical binding and chemical adsorption of myofibrillar proteins and volatile flavor substances, as well as clarifies the regulation law of flavor substances from the viewpoint of endogenous flavor characteristics and exogenous environment factors, to provide a theoretical reference for the flavor regulation of meat products.

Endothelial POFUT1 controls injury-induced liver fibrosis by repressing fibrinogen synthesis.

BACKGROUND & AIMS: NOTCH signaling in liver sinusoidal endothelial cells (LSECs) regulates liver fibrosis, a pathological feature of chronic liver diseases. POFUT1 is an essential regulator of NOTCH signaling. Here, we investigated the role of LSEC-expressed POFUT1 in liver fibrosis. METHODS: Endothelial-specific Pofut1 knockout mice were generated and experimental liver fibrosis was induced by chronic carbon tetrachloride exposure or common bile duct ligation. Liver samples were assessed by ELISA, histology, electron microscopy, immunostaining and RNA in situ hybridization. LSECs and hepatic stellate cells (HSCs) were isolated for gene expression analysis by RNA sequencing, qPCR, and western blotting. Signaling crosstalk between LSECs and HSCs was investigated by treating HSCs with supernatant from LSEC cultures. Liver single-cell RNA sequencing datasets from patients with cirrhosis and healthy individuals were analyzed to evaluate the clinical relevance of gene expression changes observed in mouse studies. RESULTS: POFUT1 loss promoted injury-induced LSEC capillarization and HSC activation, leading to aggravated liver fibrosis. RNA sequencing analysis revealed that POFUT1 deficiency upregulated fibrinogen expression in LSECs. Consistently, fibrinogen was elevated in LSECs of patients with cirrhosis. HSCs treated with supernatant from LSECs of Pofut1 null mice showed exacerbated activation compared to those treated with supernatant from control LSECs, and this effect was attenuated by knockdown of fibrinogen or by pharmacological inhibition of fibrinogen receptor signaling, altogether suggesting that LSEC-derived fibrinogen induced the activation of HSCs. Mechanistically, POFUT1 loss augmented fibrinogen expression by enhancing NOTCH/HES1/STAT3 signaling. CONCLUSIONS: Endothelial POFUT1 prevents injury-induced liver fibrosis by repressing the expression of fibrinogen, which functions as a profibrotic paracrine signal to activate HSCs. Therapies targeting the POFUT1/fibrinogen axis offer a promising strategy for the prevention and treatment of fibrotic liver diseases. IMPACT AND IMPLICATIONS: Paracrine signals produced by liver vasculature play a major role in the development of liver fibrosis, which is a pathological hallmark of most liver diseases. Identifying those paracrine signals is clinically relevant in that they may serve as therapeutic targets. In this study, we discovered that genetic deletion of Pofut1 aggravated experimental liver fibrosis in mouse models. Moreover, fibrinogen was identified as a downstream target repressed by Pofut1 in liver endothelial cells and functioned as a novel paracrine signal that drove liver fibrosis. In addition, fibrinogen was found to be relevant to cirrhosis and may serve as a potential therapeutic target for this devastating human disease.

Williams-Beuren syndrome in pediatric T-cell acute lymphoblastic leukemia: A rare case report and review of literature.

BACKGROUND: Williams-Beuren syndrome (WBS) is a rare genetic disorder caused by hemizygous microdeletion of contiguous genes on chromosome 7q11.23. Although the phenotype features extensive heterogeneity in severity and performance, WBS is not considered to be a predisposing factor for cancer development. Currently, hematologic cancers, mainly Burkitt lymphoma, are rarely reported in patients with WBS. Here in, we report a unique case of T-cell acute lymphoblastic leukemia in a male child with WBS. METHODS: This retrospective study analyzed the clinical data of this case receiving chemotherapy were analyzed. This is a retrospective study. RESULTS: The patient, who exhibited a typical WBS phenotype and presented with hemorrhagic spots. Chromosomal genome-wide chip analysis (CMA) revealed abnormalities on chromosomes 7 and 9. The fusion gene STIL-TAL1 and mutations in BCL11B, NOTCH1, and USP7 have also been found and all been associated with the occurrence of T-cell leukemia. The patient responded well to the chemotherapy. CONCLUSION: To the best of our knowledge, this is the first reported case of WBS in T-cell acute lymphoblastic leukemia. We want to emphasize that the occurrence of leukemia in this patient might be related to the loss of 7q11.23 and microdeletion of 9p21.3 (including 3 TSGs), but the relationship between WBS and malignancy remains unclear. Further studies are required to clarify the relationship between WBS and malignancy.

Identification of copy number variations among fetuses with isolated ultrasound soft markers in pregnant women not of advanced maternal age.

BACKGROUND: Pathogenic (P) copy number variants (CNVs) may be associated with second-trimester ultrasound soft markers (USMs), and noninvasive prenatal screening (NIPS) can enable interrogate the entire fetal genome to screening of fetal CNVs. This study evaluated the clinical application of NIPS for detecting CNVs among fetuses with USMs in pregnant women not of advanced maternal age (AMA). RESULTS: Fetal aneuploidies and CNVs were identified in 6647 pregnant women using the Berry Genomics NIPS algorithm.Those with positive NIPS results underwent amniocentesis for prenatal diagnosis. The NIPS and prenatal diagnosis results were analyzed and compared among different USMs. A total of 96 pregnancies were scored positive for fetal chromosome anomalies, comprising 37 aneuploidies and 59 CNVs. Positive predictive values (PPVs) for trisomy 21, trisomy 18, trisomy 13, and sex chromosome aneuploidies were 66.67%, 80.00%, 0%, and 30.43%, respectively. NIPS sensitivity for aneuploidies was 100%. For CNVs, the PPVs were calculated as 35.59% and false positive rate of 0.57%. There were six P CNVs, two successfully identified by NIPS and four missed, of which three were below the NIPS resolution limit and one false negative. The incidence of aneuploidies was significantly higher in fetuses with absent or hypoplastic nasal bone, while that of P CNVs was significantly higher in fetuses with aberrant right subclavian artery (ARSA), compared with other groups. CONCLUSIONS: NIPS yielded a moderate PPV for CNVs in non-AMA pregnant women with fetal USM. However, NIPS showed limited ability in identifying P CNVs. Positive NIPS results for CNVs emphasize the need for further prenatal diagnosis. We do not recommend the use of NIPS for CNVs screening in non-AMA pregnant women with fetal USM, especially in fetuses with ARSA.

Polysaccharides from Chinese herbal medicine: a review on the hepatoprotective and molecular mechanism.

Polysaccharides, predominantly extracted from traditional Chinese medicinal herbs such as Lycium barbarum, Angelica sinensis, Astragalus membranaceus, Dendrobium officinale, Ganoderma lucidum, and Poria cocos, represent principal bioactive constituents extensively utilized in Chinese medicine. These compounds have demonstrated significant anti-inflammatory capabilities, especially anti-liver injury activities, while exhibiting minimal adverse effects. This review summarized recent studies to elucidate the hepatoprotective efficacy and underlying molecular mechanisms of these herbal polysaccharides. It underscored the role of these polysaccharides in regulating hepatic function, enhancing immunological responses, and improving antioxidant capacities, thus contributing to the attenuation of hepatocyte apoptosis and liver protection. Analyses of molecular pathways in these studies revealed the intricate and indispensable functions of traditional Chinese herbal polysaccharides in liver injury management. Therefore, this review provides a thorough examination of the hepatoprotective attributes and molecular mechanisms of these medicinal polysaccharides, thereby offering valuable insights for the advancement of polysaccharide-based therapeutic research and their potential clinical applications in liver disease treatment.

Reliability, validity, and simplification of the Chinese version of the Global Pain Scale in patients with rheumatoid arthritis.

BACKGROUND: Persistent pain is the most reported symptom in patients with rheumatoid arthritis (RA); however, effective and brief assessment tools are lacking. We validated the Chinese version of the Global Pain Scale (C-GPS) in Chinese patients with RA and proposed a short version of the C-GPS (s-C-GPS). METHOD: The study was conducted using a face-to-face questionnaire survey with a multicenter cross-sectional design from March to December 2019. Patients aged > 18 years who met the RA diagnostic criteria were included. Based on the classical test theory (CTT) and the item response theory (IRT), we assessed the validity and reliability of the C-GPS and the adaptability of each item. An s-C-GPS was developed using IRT-based computerized adaptive testing (CAT) analytics. RESULTS: In total, 580 patients with RA (mean age, 51.04 ± 24.65 years; mean BMI, 22.36 ± 4.07 kg/m2), including 513 (88.4%) women, were included. Most participants lived in a suburb (49.3%), were employed (72.2%) and married (91.2%), reported 9-12 years of education (66.9%), and had partial medical insurance (57.8%). Approximately 88.1% smoked and 84.5% drank alcohol. Analysis of the CTT demonstrated that all items in the C-GPS were positively correlated with the total scale score, and the factor loadings of all these items were > 0.870. A significant positive relationship was found between the Visual Analog Scale (VAS) and the C-GPS. IRT analysis showed that discrimination of the C-GPS was between 2.271 and 3.312, and items 6, 8, 13, 14, and 16 provided a large amount of information. Based on the CAT and clinical practice, six items covering four dimensions were included to form the s-C-GPS, all of which had very high discrimination. The s-C-GPS positively correlated with the VAS. CONCLUSION: The C-GPS has good reliability and validity and can be used to evaluate pain in RA patients from a Chinese cultural background. The s-C-GPS, which contains six items, has good criterion validity and may be suitable for pain assessment in busy clinical practice. TRIAL REGISTRATION: This cross-sectional study was registered in the Chinese Clinical Trial Registry (ChiCTR1800020343), granted on December 25, 2018.

Construction and Mechanism of IL-15-Based Coactivated Polymeric Micelles for NK Cell Immunotherapy.

Natural killer (NK) cells are an important contributor to cancer immunotherapy, but their antitumor efficacy remains suboptimal. While cytokine-based priming shows promise in enhancing NK-cell activity, its clinical translation faces many challenges, including coactivation of multiple cytokines, poor pharmacokinetics, and limited mechanistic understanding. Here, this work develops a polymeric micelle-based IL-15/IL-2 codelivery system (IL-15/2-PEG-PTMC) for NK-cell activation. In vivo studies demonstrate that half-life of IL-15 and IL-2 and the recruitment of NK cell within tumor tissue are significantly increased after PEG-PTMC loading. Coupled with the coactivation effect of IL-15 and IL-2 conferred by this system, it noticeably delays the growth of tumors compared to conventional NK-cell activation approach, that is free IL-15 and IL-2. It is also surprisingly found that cholesterol metabolism is highly involved in the NK cell activation by IL-15/2-PEG-PTMC. Following stimulation with IL-15/2-PEG-PTMC or IL-15, NK cells undergo a series of cholesterol metabolism reprogramming, which elevates the cholesterol levels on NK cell membrane. This in turn promotes the formation of lipid rafts and activates immune synapses, effectively contributing to the enhancement of NK cell's antitumor activity. It is believed that it will open a new avenue for improving the efficacy of NK cell immunotherapy by regulating cholesterol metabolism.

Maternal CHD7 gonosomal mosaicism in a fetus with CHARGE syndrome.

Parental mosaicism is important in families with de novo mutations. Herein, we report a case of fetal CHARGE syndrome (CS) with a CHD7 variant inherited from maternal CHD7 gonosomal mosaicism. The variant was detected through trio-based whole-exome sequencing and Sanger sequencing. High-depth whole-exome sequencing was performed for the identification of parental mosaicism. A novel heterozygous CHD7 nonsense mutation (c.5794G>T/ p.E1932*) was detected in the tissue from the aborted fetus. The parents were wild-type, indicating that the mutation was a de novo variant. The mutation was suspected to be the cause of the fetal CS. However, high-depth whole-exome sequencing revealed maternal gonosomal mosaicism at a variant allele frequency of 3.2%-23.3%. The variant was identified in various tissues (peripheral blood, hair follicles, buccal epithelia, and pharyngeal epithelia) from the asymptomatic mother. We confirmed maternal CHD7 gonosomal mosaicism as a genetic cause of fetal CS. Our results emphasize the importance of clinical analysis in accurately determining the parents' status in detecting the CHD7 de novo variant in fetal CS, as this analysis has vital implications for evaluating the recurrence risk for genetic counseling.

Maternal, neonatal, pregnancy outcome characteristics of pregnant women with high plasma cell-free DNA concentration in non-invasive prenatal screening: a retrospective analysis.

Objective: Cell-free DNA (cfDNA) is a useful biomarker in various clinical contexts. Herein, we aimed to identify maternal characteristics and pregnancy outcomes associated with a failed NIPS test due to high cfDNA concentrations. Methods: A retrospective study of cases with high plasma cfDNA concentration in pregnant women in which NIPS test was performed (from 174,318 cases). We reported the detection of 126 cases (118 with complete clinical information) in which the high amount of cfDNA did not allow the performance of NIPS and study the possible causes of this result. Results: 622 (0.35%) of 174,318 pregnant women had failed the NIPS test, including 126 (20.3%) cases with high plasma cfDNA concentrations. The failed NIPS due to high plasma cfDNA concentrations was associated with maternal diseases and treatment with low-molecular-weight heparin (LMWH). Further follow-up of the 118 pregnant women in the case group revealed that the pregnancy outcomes included 31 premature deliveries, 21 abortions. The cfDNA concentrations of pregnant women with preterm deliveries were 1.15 (0.89, 1.84), which differed significantly from those who had full-term deliveries. Conclusions: Among pregnant women with high cfDNA concentrations, systemic autoimmune diseases, pregnancy complications and LMWH were associated with increased incidence of failed NIPS test. High maternal cfDNA concentrations may not be associated with chromosomal abnormalities in the fetus. However, they should be alerted to the possibility of preterm births and stillbirths. Further clinical studies on pregnant women with high cfDNA concentrations are required.

Optimizing postbiotic production through solid-state fermentation with Bacillus amyloliquefaciens J and Lactiplantibacillus plantarum SN4 enhances antibacterial, antioxidant, and anti-inflammatory activities.

Background: Postbiotics are an emerging research interest in recent years and are fairly advanced compared to prebiotics and probiotics. The composition and function of postbiotics are closely related to fermentation conditions. Methods: In this study, we developed a solid-state fermentation preparation method for postbiotics with antimicrobial, antioxidant, and anti-inflammatory activities. The antibacterial activity was improved 3.62 times compared to initial fermentation conditions by using optimization techniques such as single factor experiments, Plackett-Burman design (PBD), steepest ascent method (SAM), and central composite design (CCD) methods. The optimized conditions were carried out with an initial water content of 50% for 8 days at 37°C and fermentation strains of Bacillus amyloliquefaciens J and Lactiplantibacillus plantarum SN4 at a ratio of 1:1 with a total inoculum size of 8%. The optimized SSF medium content ratios of peptide powder, wheat bran, corn flour, and soybean meal were 4, 37.4, 30, and 28.6%, respectively. Results: Under these optimized conditions, postbiotics with a concentration of 25 mg/mL showed significant broad-spectrum antibacterial capabilities against Escherichia coli, Salmonella, and Staphylococcus aureus and strong antioxidant activity against ABTS, DPPH, and OH radicals. Moreover, the optimized postbiotics exhibited good anti-inflammatory ability for reducing nitric oxide (NO) secretion in RAW 264.7 macrophage cells in response to LPS-induced inflammation. Furthermore, the postbiotics significantly improved intestinal epithelial wound healing capabilities after mechanical injury, such as cell scratches in IPEC-J2 cells (p < 0.05). Conclusion: In brief, we developed postbiotics through optimized solid-state fermentation with potential benefits for gut health. Therefore, our findings suggested that the novel postbiotics could be used as potential functional food products for improving body health.

Effect of ultrasonic treatment on the quality of Mianning ham.

This paper investigates the optimal process for ultrasonic desalination of Mianning ham. The study analyzed various factors such as ultrasonic treatment time, temperature, and power to determine their impact on the rate of desalination of hams. A single factor test was conducted to study the rate of desalination. Further, A Box-Behnken experimental design was used to evaluate the effect of Mianning ham desalination. The design examined the impacts of ultrasound on the physicochemical properties, texture, and sensory of the ham. Response surface processing group underwent oral processing to determine the optimal ultrasonic treatment conditions with the highest acceptance level. The results show that the best conditions were: ultrasonic time 84.56 min, ultrasonic temperature 40.35°C, and ultrasonic power 150.85 W. The average desalination rate of the ham under the optimal conditions was 25.93% ± 0.69%, and the hardness was 4.48 N ± 0.62 N. Overall, this process significantly improved the desalination rate, texture, and sensory quality of Mianning ham, providing solid theoretical support for desalination processing at the back end of ham.

Efficacy and safety comparison between axillary lymph node dissection with no axillary surgery in patients with sentinel node-positive breast cancer: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to study the evidence on the efficacy and safety of omitting axillary lymph node dissection (ALND) for patients with clinically node-negative but sentinel lymph node (SLN)-positive breast cancer using all the available evidence. METHODS: The Embase, Medline, and Cochrane Library databases were searched through February 25, 2023. Original trials that compared only the sentinel lymph node biopsy (SLNB) with ALND as the control group for patients with clinically node-negative but SLN-positive breast cancer were included. The primary outcomes were axillary recurrence rate, total recurrence rate, disease-free survival (DFS), and overall survival (OS). Meta-analyses were performed to compare the odds ratio (OR) in rates and the hazard ratios (HR) in time-to-event outcomes between both interventions. Based on different study designs, tools in the revised Cochrane risk of bias tool were used for randomized trials and the risk of bias in nonrandomized studies of interventions to assess the risk of bias for each included article. Funnel plots and Egger's test were used for the publication's bias assessment. RESULTS: In total, 30 reports from 26 studies were included in the systematic review (9 reports of RCTs, 21 reports of retrospective cohort studies). According to our analysis, omitting ALND in patients with clinically node-negative but SLN-positive breast cancer had a similar axillary recurrence rate (OR = 0.95, 95% confidence interval (CI): 0.76-1.20), DFS (HR = 1.02, 95% CI: 0.89-1.16), and OS (HR = 0.97, 95% CI: 0.92-1.03), but caused a significantly lower incidence of adverse events and benefited in locoregional recurrence rate (OR = 0.76, 95% CI: 0.59-0.97) compared with ALND. CONCLUSION: For patients with clinically node-negative but SLN-positive breast cancer (no matter the number of the positive SLN), this review showed that SLNB alone had a similar axillary recurrence rate, DFS, and OS, but caused a significantly lower incidence of adverse events and showed a benefit for the locoregional recurrence compared with ALND. An OS benefit was found in the Macro subset that used SLNB alone versus complete ALND. Therefore, omitting ALND is feasible in this setting. TRIAL REGISTRATION: CRD 42023397963.