Clinical characteristics and surgical treatment of children with 45, X/46, XY differences of sex development.

OBJECTIVE: This study retrospectively analyzes the clinical data of 18 children with 45,X/46,XY differences of sex development (DSD), summarizes their clinical features and explores gonadal and Müllerian duct remnants surgical treatment methods. METHODS: The clinical data of 18 children with karyotype 45,X/46,XY diagnosed in the Department of Urology of Hunan Children's Hospital from March 2011 to October 2021 were collected. All children underwent HCG stimulation testing, laparoscopic exploration, urethroscopy and bilateral gonadal biopsy. After DSD multidisciplinary team (MDT) meeting, some children underwent gonadectomy and genitalia reconstructive surgeries. RESULTS: The median age at first diagnosis was 1 year and 4 months (range: 10 months ∼ 16 years and 3 months). 5 children presented with female gender; they all maintained their gender assignment. The external masculinisation score (EMS) of patients raised as female was 1 (0∼3) [median (range)]. 13 children presented with male gender, 10 maintained a male gender, 3 were assigned a neutral gender. The EMS of the children raised as male was 5 (2-8) [median (range)], the EMS of the children raised as neutral gender was 4 (3.5-9.5) [median (range)]. The HCG stimulation test was positive in 11 cases, partially positive in 2 case, and negative in 5 cases. There was no relationship between the percentage of chimerism (45X ratio) and the appearance and severity of genital abnormalities. (t=-1.08, P=0.298). There was 1 case of complete gonadal dysgenesis (CGD), 10 cases of mixed gonadal dysgenesis (MGD), 5 cases of partial gonadal dysgenesis (PGD), 1 case of bilateral normal testes and 1 case of ovotesticular DSD (split-lateral type). No gonadal specimen showed germ cell tumor changes. Five cases selected to maintain the female gender, among which 3 cases underwent bilateral gonadectomy and genitalia reconstructive surgeries. Among the 10 children who chose to maintain the male gender, unilateral streak gonadectomy was performed in 4 (57.1%) with MGD, unilateral dysgenetic orchiectomy in 1 (25%) with PGD, and right ovariectomy in 1 with OTDSD. Nine of them underwent genitalia reconstructive surgeries. Four of them preserved their uterus and vagina did not have any complications during the follow-up period. CONCLUSION: Hypospadias combined with cryptorchidism and residual Müllerian duct structures is the most common phenotype of children with 45, X/46, XY DSD. Mixed gonadal dysgenesis (MGD) is the most common gonadal type. Gender assignment should be carefully selected after a thorough evaluation, while genitalia reconstructive surgery can be considered in selected patients. In children who choose the male gender, the Müllerian duct can be preserved.

SME-MFP: A novel spatiotemporal neural network with multiangle initialization embedding toward multifunctional peptides prediction.

As a promising alternative to conventional antibiotic drugs in the biomedical field, functional peptide has been widely used in disease treatment owing to its low toxicity, high absorption rate, and biological activity. Recently, several machine learning methods have been developed for functional peptide prediction. However, the main research heavily relies on statistical features and few consider multifunctional peptide identification. So, we propose SME-MFP, a novel predictor in the imbalanced multi-label functional peptide datasets. First, we employ physicochemical and evolutionary information to represent the peptide sequence's initialization features from multiple perspectives. Second, the features are fused and then put into spatial feature extractors, where the residual connection and multiscale convolutional neural network extract more discriminative features of different lengths' peptide sequences. Besides, we also design AFT-based temporal feature extractors to fully capture the global interactions of the sequences. Finally, devising a new loss to replace the traditional cross entropy loss to settle the class imbalance problems. The results show that our framework not only enhances the model's ability to capture sequence features effectively, but also accuracy improves by 3.89% over existing methods on public peptide datasets.

Draining Lymph Node Metastasis Model for Assessing the Dynamics of Antigen-Specific CD8+ T Cells During Tumorigenesis.

Tumor antigen-specific CD8+ T cells from draining lymph nodes gain an accumulating importance in mounting anti-tumor immune response during tumorigenesis. However, in many cases, cancer cells form metastatic loci in lymph nodes before further metastasizing to distant organs. To what extent the local and systematic CD8+ T cell responses were influenced by LN metastasis remains obscure. To this end, we set up a murine LN metastasis model combined with a B16F10-GP melanoma cell line expressing the surrogate neoantigen derived from lymphocytic choriomeningitis virus (LCMV), glycoprotein (GP), and P14 transgenic mice harboring T cell receptors (TCRs) specific to GP-derived peptide GP33-41 presented by the class I major histocompatibility complex (MHC) molecule H-2Db. This protocol enables the study of antigen-specific CD8+ T cell responses during LN metastasis. In this protocol, C57BL/6J mice were subcutaneously implanted with B16F10-GP cells, followed by adoptive transfer with naive P14 cells. When the subcutaneous tumor grew to approximately 5 mm in diameter, the primary tumor was excised, and B16F10-GP cells were directly injected into the tumor draining lymph node (TdLN). Then, the dynamics of CD8+ T cells were monitored during the process of LN metastasis. Collectively, this model has provided an approach to precisely investigate the antigen-specific CD8+ T cell immune responses during LN metastasis.

Correlation Between DCAMKL-1 Protein Expression and K-ras Gene Mutation in Colorectal Cancer.

Aim: To investigate the correlation between doublecortin and CaM kinase-like-1 (DCAMKL-1) protein expression, K-ras gene mutation, and their impact on patient prognosis in colorectal cancer (CRC). Methods: Immunohistochemistry was used to detect the expression of DCAMKL-1 protein in 60 cases of colorectal adenoma, 82 cases of CRC (including 65 cases of lymph node metastasis) and paraffin-embedded paracancerous intestinal mucosal tissue. K-ras gene mutations in primary CRC lesions were detected using an amplification-refractory mutation system and fluorescent polymerase chain reaction. The relationship between DCAMKL-1 protein expression and K-ras gene mutations with the clinicopathological characteristics of patients with CRC was analyzed. Univariate Kaplan‒Meier survival analysis and multivariate Cox regression analysis were performed using follow-up data. Results: The mutation rate of the K-ras gene in 82 cases of CRC was 48.8% (40/82). The positivity rate for the presence of DCAMKL-1 protein in CRC was 70.7% (58/82), significantly higher than that for colorectal adenomas (53.3%; 32/60) and paracancerous intestinal mucosa (0%; 0/82) (P<0.05). The positive expression rate for the presence of DCAMKL-1 protein in 65 patients with lymph node metastasis was higher in the primary lesions (69.2%; 45/65) than in the lymph node metastases (52.3%; 34/65) (χ2=12.087, P=0.001). The K-ras gene mutation status was positively correlated with DCAMKL-1 protein expression (r=0.252, P=0.022). Conclusion: In this study, a potential positive correlation between K-ras gene mutation and DCAMKL-1 protein expression was identified in CRC tissues. The assessment of K-ras gene mutation status and DCAMKL-1 protein expression holds promise for augmenting early diagnosis and prognosis evaluation in CRC. This approach may improve the overall prognosis and survival outcomes for CRC patients.

Clinical Application of Ureteroscope-Assisted Laparoscopic Surgery for Prostatic Utricle in Children.

Purpose: To investigate the use of ureteroscope-assisted laparoscopic surgery (UALS) in treating symptomatic prostatic utricle (PU) in children. Materials and Methods: Data on surgically treated cases of PU at the Department of Urology in Hunan Children's Hospital between September 2014 and September 2022 were retrospectively collected and analyzed. The diagnosis was confirmed by cystourethroscopy followed by ureteroscopy, and PU was excised by ureteroscope-assisted laparoscopy. Results: A total of 21 patients with PU were enrolled in this study. The median age of the patients at surgery was 8.1 (4.6-11.5) years. Karyotyping was available for 15 children: 13 (86.7%) were 46XY, 1 (6.7%) was 45X/46XY, and 1 (6.7%) was 45X/46XY/47XYY. The median length of the PU was 5.0 (4.1-7.1) cm. Nineteen patients underwent only ureteroscope-assisted laparoscopic excision, whereas 2 also had a perineal incision. All excisions were successfully performed. The median intraoperative blood loss was 25.0 (20.0-37.5) mL. The median hospital stay and follow-up durations were 18.0 (14.5-25.0) days and 24.0 (13.5-49.0) months, respectively. The patients reported no postoperative clinical symptoms. Conclusion: UALS allows for accurate patient positioning and thorough exposure of the anatomical structures, and it is a safe, effective, and minimally invasive treatment for PU in children.

Risk-Factor Analysis and Prediction-Model Construction of Urethral Stricture after Hypospadias Surgery in Children: A Single-Centre Retrospective Study.

OBJECTIVE: This study aimed to explore the incidence of postoperative urethral stricture in children after hypospadias surgery, analyse its risk factors, and construct a prediction model. METHODS: We retrospectively analysed the clinical data of 402 children with hypospadias surgery in Hunan Children's Hospital from January 2022 to January 2023. To explore the risk factors of urethral stricture after hypospadias surgery in children, the incidence of postoperative urethral stricture in children was statistically analysed, and univariate and multivariate logistic regression analyses were adopted. A prediction model was established, and the prediction efficiency of the model was examined using a receiver operating characteristic curve. RESULTS: The incidence of postoperative urethral stricture in children after hypospadias surgery was 9.20% (37/402). On this basis, the children were divided into stricture group (SG, n = 37) and normal group (NG, n = 365). Both groups had overt differences in disease classification, urinary tract infection, indwelling-catheter time, and surgical methods (p < 0.05). Logistic regression analysis showed that urinary tract infection, surgical methods, and long indwelling-catheter time were the risk factors (p < 0.001). The prediction model constructed based on the above results had certain prediction efficiency. CONCLUSIONS: More attention should be paid to children with urinary tract infection, high-risk surgery, and long indwelling-catheter time after hypospadias surgery. Our prediction model can serve as an effective reference for evaluating the occurrence of postoperative urethral stricture.

Risk factors for postoperative complications following one-stage proximal hypospadias repair involving the disconnection of the urethral plate: a retrospective study.

BACKGROUND: Children with hypospadias are at risk of serious physical and mental health problems, including abnormal urination, sexual dysfunction, and infertility. The sole available treatment is the surgical restoration of genital appearance and function. Proximal hypospadias (PH) correction is more challenging and carries a higher risk of complications than does distal hypospadias correction, with a higher likelihood of postoperative complications requiring additional surgery, resulting in considerable economic and psychological strain for families. Herein, we aimed to identify factors associated with complications following one-stage PH repair with urethral plate disconnection. METHODS: We retrospectively analyzed data from 236 children who underwent PH repair at our center between December 2020 and December 2022. We collected information on age, surgical procedure, length of the reconstructed urethra (LRU), glans width (GW), ventral curvature, surgical approach, preoperative androgen use, suture type, presence of prostatic utricle, body mass index, season of surgery, anesthesia type, low birth weight, preterm birth, follow-up period, and complications. Surgical complications included urethral fistulas, urethral diverticula, anastomotic strictures, urethral strictures, glans dehiscence, and penile curvature recurrences. The study population was divided into complication and no-complication groups, and univariate and multivariate analyses were conducted. RESULTS: Of the 236 patients with PH who had a median follow-up of 10.0 (8.0, 14.0) months, 79 were included (33.5%) in the complication group and 157 were included (66.5%) in the no-complication group. In the univariate analysis, age (P < 0.001), LRU (P < 0.001), degree of penile curvature (P = 0.049), and PH with prostatic utricle (P = 0.014) were significantly associated with complications after PH repair. In the multivariate logistic regression analysis, LRU (P<0.001, odds ratio [OR] = 3.396, 95% confidence interval [CI]: 2.229-5.174) and GW (P = 0.004, OR = 0.755, 95%CI: 0.625-0.912) were independent factors influencing postoperative complications. The optimal LRU threshold was 4.45 cm (area under the curve, 0.833; sensitivity, 0.873; specificity, 0.873; P<0.001, OR = 3.396, 95% CI: 2.229-5.174). CONCLUSIONS: LRU and GW are independent factors affecting PH complications. An LRU of < 4.45 cm and an increased GW can reduce the risk of complications.

The Mechanics of Tumor Cells Dictate Malignancy via Cytoskeleton-Mediated APC/Wnt/ß-Catenin Signaling.

Tumor cells progressively remodel cytoskeletal structures and reduce cellular stiffness during tumor progression, implicating the correlation between cell mechanics and malignancy. However, the roles of tumor cell cytoskeleton and the mechanics in tumor progression remain incompletely understood. We report that softening/stiffening tumor cells by targeting actomyosin promotes/suppresses self-renewal in vitro and tumorigenic potential in vivo. Weakening/strengthening actin cytoskeleton impairs/reinforces the interaction between adenomatous polyposis coli (APC) and ß-catenin, which facilitates ß-catenin nuclear/cytoplasmic localization. Nuclear ß-catenin binds to the promoter of Oct4, which enhances its transcription that is crucial in sustaining self-renewal and malignancy. These results demonstrate that the mechanics of tumor cells dictate self-renewal through cytoskeleton-APC-Wnt/ß-catenin-Oct4 signaling, which are correlated with tumor differentiation and patient survival. This study unveils an uncovered regulatory role of cell mechanics in self-renewal and malignancy, and identifies tumor cell mechanics as a hallmark not only for cancer diagnosis but also for mechanotargeting.

Particle Size-Controlled Oxygen Reduction and Evolution Reaction Nanocatalysts Regulate Ru(bpy)32+'s Dual-potential Electrochemiluminescence for Sandwich Immunoassay.

Multiple signal strategies remarkably improve the accuracy and efficiency of electrochemiluminescence (ECL) immunoassays, but the lack of potential-resolved luminophore pairs and chemical cross talk hinders their development. In this study, we synthesized a series of gold nanoparticles (AuNPs)/reduced graphene oxide (Au/rGO) composites as adjustable oxygen reduction reaction and oxygen evolution reaction catalysts to promote and modulate tris(2,2'-bipyridine) ruthenium(II) (Ru(bpy)32+)'s multisignal luminescence. With the increase in the diameter of AuNPs (3 to 30 nm), their ability to promote Ru(bpy)32+'s anodic ECL was first impaired and then strengthened, and cathodic ECL was first enhanced and then weakened. Au/rGOs with medium-small and medium-large AuNP diameters remarkably increased Ru(bpy)32+'s cathodic and anodic luminescence, respectively. Notably, the stimulation effects of Au/rGOs were superior to those of most existing Ru(bpy)32+ co-reactants. Moreover, we proposed a novel ratiometric immunosensor construction strategy using Ru(bpy)32+'s luminescence promoter rather than luminophores as tags of antibodies to achieve signal resolution. This method avoids signal cross talk between luminophores and their respective co-reactants, which achieved a good linear range of 10-7 to 10-1 ng/ml and a limit of detection of 0.33 fg/ml for detecting carcinoembryonic antigen. This study addresses the previous scarcity of the macromolecular co-reactants of Ru(bpy)32+, broadening its application in biomaterial detection. Furthermore, the systematic clarification of the detailed mechanisms for converting the potential-resolved luminescence of Ru(bpy)32+ could facilitate an in-depth understanding of the ECL process and should inspire new designs of Ru(bpy)32+ luminescence enhancers or applications of Au/rGOs to other luminophores. This work removes some impediments to the development of multisignal ECL biodetection systems and provides vitality into their widespread applications.

Development of homozygous tetraploid potato and whole genome doubling-induced the enrichment of H3K27ac and potentially enhanced resistance to cold-induced sweetening in tubers.

Polyploid plants typically display advantages on some agronomically important traits over their diploid counterparts. Extensive studies have shown genetic, transcriptomic, and epigenetic dynamics upon polyploidization in multiple plant species. However, few studies have unveiled those alternations imposed only by ploidy level, without any interference from heterozygosity. Cultivated potato is highly heterozygous. Thus, in this study, we developed two homozygous autotetraploid lines and one homozygous diploid line in parallel from a homozygous diploid potato. We confirmed their ploidy levels using chloroplast counting and karyotyping. Oligo-FISH and genome re-sequencing validated that these potato lines are nearly homozygous. We investigated variations in phenotypes, transcription, and histone modifications between two ploidies. Both autotetraploid lines produced larger but fewer tubers than the diploid line. Interestingly, each autotetraploid line displayed ploidy-related differential expression for various genes. We also discovered a genome-wide enrichment of H3K27ac in genic regions upon whole-genome doubling (WGD). However, such enrichment was not associated with the differential gene expression between two ploidies. The tetraploid lines may exhibit better resistance to cold-induced sweetening (CIS) than the diploid line in tubers, potentially regulated through the expression of CIS-related key genes, which seems to be associated with the levels of H3K4me3 in cold-stored tubers. These findings will help to understand the impacts of autotetraploidization on dynamics of phenotypes, transcription, and histone modifications, as well as on CIS-related genes in response to cold storage.

A diagnostic model of autoimmune hepatitis in unknown liver injury based on noninvasive clinical data.

All the diagnostic criteria of autoimmune hepatitis (AIH) include histopathology. However, some patients may delay getting this examination due to concerns about the risks of liver biopsy. Therefore, we aimed to develop a predictive model of AIH diagnostic that does not require a liver biopsy. We collected demographic, blood, and liver histological data of unknown liver injury patients. First, we conducted a retrospective cohort study in two independent adult cohorts. In the training cohort (n = 127), we used logistic regression to develop a nomogram according to the Akaike information criterion. Second, we validated the model in a separate cohort (n = 125) using the receiver operating characteristic curve, decision curve analysis, and calibration plot to externally evaluate the performance of this model. We calculated the optimal cutoff value of diagnosis using Youden's index and presented the sensitivity, specificity, and accuracy to evaluate the model in the validation cohort compared with the 2008 International Autoimmune Hepatitis Group simplified scoring system. In the training cohort, we developed a model to predict the risk of AIH using four risk factors-The percentage of gamma globulin, fibrinogen, age, and AIH-related autoantibodies. In the validation cohort, the areas under the curve for the validation cohort were 0.796. The calibration plot suggested that the model had an acceptable accuracy (p > 0.05). The decision curve analysis suggested that the model had great clinical utility if the value of probability was 0.45. Based on the cutoff value, the model had a sensitivity of 68.75%, a specificity of 76.62%, and an accuracy of 73.60% in the validation cohort. While we diagnosed the validated population by using the 2008 diagnostic criteria, the sensitivity of prediction results was 77.77%, the specificity was 89.61% and the accuracy was 83.20%. Our new model can predict AIH without a liver biopsy. It is an objective, simple and reliable method that can effectively be applied in the clinic.

Circ_0058063 regulates the development of esophageal cancer through miR-377-3p/HOXA1 axis.

Esophageal cancer is one of the deadliest cancers. Circular RNA (CircRNA) can be used as a tumor marker. Therefore, this provides an important idea for our research. Real-time quantitative PCR (RT-qPCR) was used to analyze the expression of circ_0058063, miR-377-3p and homeobox protein Hox-A1 (HOXA1), western blot was used to analyze the protein levels of HOXA1 and cyclinD1, B cell leukemia/lymphoma 2 associated X (Bax). Cell Counting Kit-8 (CCK-8) assay, colony formation assay and wound healing assay were used to analyze cell proliferation and migration; apoptosis was analyzed by flow cytometry. Dual-luciferase reporter assays were performed to analyze the luciferase activities. Transwell assay was used to analyze the cell invasion. A glycolysis metabolism assay was used to analyze cell glycolysis ability. Xenograft models were used to validate the effect of circ_0009035 in the growth of esophageal cancer in vivo . Circ_0009035 and HOXA1 were upregulated, while miR-377 was downregulated in esophageal cancer.. Circ_0058063 targeted miR-377-3p, and HOX4 was a target of miR-377-3p. Knockdown of circ_0058063 inhibited migration, invasion and proliferation and promoted apoptosis of esophageal cancer cells. MiR-377-3p inhibition or HOXA1 overexpression could restore the effect of si-circ_0058063 on esophageal cancer cells. Knockdown of circ_0058063 repressed the growth of esophageal cancer tumors in vivo. Our study found that circ_0058063 could regulate the expression of HOXA1 by targeting miR-377-3p, thereby affecting the progress of esophageal cancer.

Testicular regression syndrome: A retrospective analysis of clinical and histopathological features in 570 cases.

This study aimed to analyze the clinical features and pathological findings of the largest reported case series of testicular regression syndrome (TRS). Data, including age, affected side, color Doppler ultrasound results, surgical methods, intraoperative conditions, and pathological examinations, of children with unilateral TRS who were treated in our center from December 2012 to November 2021 were retrospectively analyzed. A total of 570 patients were included in this study. The mean age at surgery was 38 (range, 5-193) months. There were 457 cases (80.2%) of left TRS. Preoperative color Doppler ultrasonography found nubbins in 172 cases (30.2%). The long diameter of the contralateral testis was 17.11 (±4.22) mm, and the volume was 0.81 (±1.15) ml. The long diameter was ≥1.6 cm in 62.0% of the patients (240/387) aged ≤3 years. Laparoscopy was performed as the initial surgical step in 513 cases, of which 96.7% of the children had closed internal rings. One or more lesions of fibrosis, hemosiderin, and calcification were found in 92.4% (474/513) of the excised remnants. Germ cells were present in 16 cases (3.1%). In conclusion, TRS is more common on the left side and is usually accompanied by a closed internal ring and compensatory hypertrophy of the contralateral testis. Germ cells are only present in cases where the spermatic vessels enters the internal ring. We recommend that further exploration and excision of the remnants may not be applicable in cases where only the vas deferens has entered the internal ring.

A study on the differences in radon exhalation of different lithologies at various depths and the factors influencing its distribution in northern Shaanxi, China.

The inhalation of a high concentration of radon gas increases the risk of cancer. Therefore, it is of utmost necessity to pay due attention to the problem of environmental radon pollution. The high radioactivity above the coal slab causes serious radon radiation contamination on the mining grounds in coal mining areas such as the northern part of China and the western part of the United States. At present, there is a lack of research on radon exhalation in different lithologies. In this study, the differences in the radon exhalation of different lithologies at various depths and their controlling factors were studied by NMR and radon measurement. The results highlighted that the radon exhalation rates in different rocks varied from 0.3 to 0.6 Bq/m2·s. The average radon exhalation rate of the soil was 0.7 Bq/m2·s, and the radon exhalation rates of different lithologies followed the pattern red clay > loess > sandstone > mudstone > coal. The radon exhalation rate increased initially, followed by a decrease, and the radon exhalation rate was the highest at the boundary between the soil and rock layers. The radon exhalation rates of different lithologies have a strong correlation with the small pores (<0.1 µm), which govern the changes in the porous structure with depth. The results of this study are important from the perspective evaluation of environmental radon pollution.

Clinical Efficacy of Laparoscopic Orchiopexy With the Modified Prentiss Maneuver for Non-palpable Testis Near the Internal Ring.

Objective: To compare the clinical efficacy and safety of laparoscopic orchiopexy with the modified Prentiss maneuver (LOMPM) and laparoscopic trans-inguinal orchiopexy (LTIO) for the treatment of non-palpable testis (NPT) <1 cm from the internal ring. Methods: Children with unilateral NPT who underwent laparoscopic orchiopexy at our center between February 2018 and January 2021 were retrospectively analyzed. According to the surgical method, they were divided into LOMPM and LTIO groups. The operation time, postoperative pain degree, postoperative complications and follow-up results were compared between the two groups. Results: A total of 98 patients were included in this study, including 41 cases in the LOMPM group and 57 cases in the LTIO group. All patients underwent successful surgery. The LOMPM group was superior to the LTIO group in terms of postoperative testicular position (lower scrotm: 90.2 vs. 71.9%, P = 0.026). There were no significant differences in operation time, postoperative pain score, and complications between the two groups. Preoperative testicular volume, postoperative testicular volume, and testicular growth rate in the LOMPM group were comparable to those in the LTIO group. There were no testicular atrophy, inguinal hernia and hydrocele in both groups after operation. Conclusions: LOMPM was comparable in safety to LTIO, but LOMPM had a good post-operative testicular position, and was suitable for the treatment of NPT near the internal ring.

Ultrasound combined with nanobubbles promotes systemic anticancer immunity and augments anti-PD1 efficacy.

BACKGROUND: The poor immunogenicity of solid tumors limits the efficacy ofanti-programmed cell death protein 1 (anti-PD1)-based immune checkpoint blockade (ICB); thus, less than 30% of patients with cancer exhibit a response. Currently, there is still a lack of effective strategies for improving tumor immunogenicity. METHODS: The antitumor effect of ultrasound-stimulated nanobubbles (USNBs) alone and in combination with an anti-PD1 antibody was evaluated in RM1 (prostate cancer), MC38 (colon cancer) and B16 (melanoma) xenograft mouse models. The phenotypes of antigen-presenting cells and CD8+ T cells were evaluated by flow cytometry. Damage-associated molecular pattern (DAMP) release, antigen release and tumor cell necrosis were assessed via western blot, flow cytometry, transmission electron microscopy and confocal microscopy. RESULTS: USNB promoted the infiltration and antitumor activity of CD8+ T cells. The combination of USNB and anti-PD1 blockade improved systemic antitumor immunity and resulted in an abscopal effect and long-term immune memory protection after complete tumor remission. Mechanistically, tumor-targeting USNB induced tumor cell necrosis through an ultrasound-mediated cavitation effect, which significantly increased DAMP release and tumor antigen presentation, consequently sensitizing tumors to ICB treatment. CONCLUSION: The administration of USNB increased tumor immunogenicity by remodeling the tumor-immune microenvironment, providing a promising strategy for sensitizing poorly immunogenic solid tumors to immunotherapy in the clinic.

Enhancement effect of defoamer additives on photo-fermentation biohydrogen production process.

Foaming is a key issue should be solved in the process of photo-fermentation biohydrogen production (PFHP), since it has negative influence on the hydrogen yield potential, especially when taken straw as substrate. Appropriate foam control measures must be considered for industrialization. Hence, in this work, foam height and biohydrogen yield were selected as index, the effect of defoamer addition on PFHP was investigated. The defoamer has no negative effect on bacterial growth. In the addition range of 0-1 mL/L, the higher addition amount, indicates better foam control effect. The maximum foam height could be reduced by 55% and the foam existence time by 36 h. The reduction of foam was beneficial to biohydrogen production, and the highest cumulative hydrogen yield was increased 23% at the addition level of 0.125 mL/L.

DeepSeqPanII: An Interpretable Recurrent Neural Network Model With Attention Mechanism for Peptide-HLA Class II Binding Prediction.

Human leukocyte antigen (HLA) complex molecules play an essential role in immune interactions by presenting peptides on the cell surface to T cells. With significant deep learning progress, a series of neural network-based models have been proposed and demonstrated with their excellent performances for peptide-HLA class I binding prediction. However, there is still a lack of effective binding prediction models for HLA class II protein binding with peptides due to its inherent challenges. We present a novel sequence-based pan-specific neural network structure, DeepSeaPanII, for peptide-HLA class II binding prediction in this work. Our model is an end-to-end neural network model without the need for pre-or post-processing on input samples compared with existing pan-specific models. Besides state-of-the-art performance in binding affinity prediction, DeepSeqPanII can also extract biological insight on the binding mechanism over the peptide by its attention mechanism-based binding core prediction capability. The leave-one-allele-out cross-validation and benchmark evaluation results show that our proposed network model achieved state-of-the-art performance in HLA-II peptide binding. The source code and trained models are freely available at https://github.com/pcpLiu/DeepSeqPanII.