The evolution, complexity, and diversity of swine influenza viruses in China: A hidden public health threat.

Swine influenza viruses (SIVs), including H1N1, H1N2, and H3N2, have spread throughout the global pig population. Potential pandemics are a concern with the recent sporadic cross-species transmission of SIVs to humans. We collected 1421 samples from Guangdong, Fujian, Henan, Yunnan and Jiangxi provinces during 2017-2018 and isolated 29 viruses. These included 21H1N1, 5H1N2, and 3H3N2 strains. Genome analysis showed that the domestic epidemic genotypes of H1N1 were mainly G4 and G5 reassortant EA swine H1N1. These genotypes have a clear epidemic advantage. Two strains were Clade 6B.1 pdm/09H1N1, suggesting a possible pig-to-human transmission route. Notably, three new H1N2 genotypes were identified using the genomic backbones of G4 or G5 viruses for recombination. The identification of various subtypes and genotypes highlight the complexity and diversity of SIVs in China and need for continuous monitoring of SIV evolution to assess the risks and prepare for potential influenza pandemics.

Breaking the barrier: Nanoparticle-enhanced radiotherapy as the new vanguard in brain tumor treatment.

The pursuit of effective treatments for brain tumors has increasingly focused on the promising area of nanoparticle-enhanced radiotherapy (NERT). This review elucidates the context and significance of NERT, with a particular emphasis on its application in brain tumor therapy-a field where traditional treatments often encounter obstacles due to the blood-brain barrier (BBB) and tumor cells' inherent resistance. The aims of this review include synthesizing recent advancements, analyzing action mechanisms, and assessing the clinical potential and challenges associated with nanoparticle (NP) use in radiotherapy enhancement. Preliminary preclinical studies have established a foundation for NERT, demonstrating that nanoparticles (NPs) can serve as radiosensitizers, thereby intensifying radiotherapy's efficacy. Investigations into various NP types, such as metallic, magnetic, and polymeric, have each unveiled distinct interactions with ionizing radiation, leading to an augmented destruction of tumor cells. These interactions, encompassing physical dose enhancement and biological and chemical radio sensitization, are crucial to the NERT strategy. Although clinical studies are in their early phases, initial trials have shown promising results in terms of tumor response rates and survival, albeit with mindful consideration of toxicity profiles. This review examines pivotal studies affirming NERT's efficacy and safety. NPs have the potential to revolutionize radiotherapy by overcoming challenges in targeted delivery, reducing off-target effects, and harmonizing with other modalities. Future directions include refining NP formulations, personalizing therapies, and navigating regulatory pathways. NERT holds promise to transform brain tumor treatment and provide hope for patients.

Deep learning-based deformable image registration with bilateral pyramid to align pre-operative and follow-up magnetic resonance imaging (MRI) scans.

Background: The evaluation of brain tumor recurrence after surgery is based on the comparison between tumor regions on pre-operative and follow-up magnetic resonance imaging (MRI) scans in clinical practice. Accurate alignment of MRI scans is important in this evaluation process. However, existing methods often fail to yield accurate alignment due to substantial appearance and shape changes of tumor regions. The study aimed to improve this misalignment situation through multimodal information and compensation for shape changes. Methods: In this work, a deep learning-based deformation registration method using bilateral pyramid to create multi-scale image features was developed. Moreover, morphology operations were employed to build correspondence between the surgical resection on the follow-up and pre-operative MRI scans. Results: Compared with baseline methods, the proposed method achieved the lowest mean absolute error of 1.82 mm on the public BraTS-Reg 2022 dataset. Conclusions: The results suggest that the proposed method is potentially useful for evaluating tumor recurrence after surgery. We effectively verified its ability to extract and integrate the information of the second modality, and also revealed the micro representation of tumor recurrence. This study can assist doctors in registering multiple sequence images of patients, observing lesions and surrounding areas, analyzing and processing them, and guiding doctors in their treatment plans.

Evolving Tumor Characteristics and Smart Nanodrugs for Tumor Immunotherapy.

Typical physiological characteristics of tumors, such as weak acidity, low oxygen content, and upregulation of certain enzymes in the tumor microenvironment (TME), provide survival advantages when exposed to targeted attacks by drugs and responsive nanomedicines. Consequently, cancer treatment has significantly progressed in recent years. However, the evolution and adaptation of tumor characteristics still pose many challenges for current treatment methods. Therefore, efficient and precise cancer treatments require an understanding of the heterogeneity degree of various factors in cancer cells during tumor evolution to exploit the typical TME characteristics and manage the mutation process. The highly heterogeneous tumor and infiltrating stromal cells, immune cells, and extracellular components collectively form a unique TME, which plays a crucial role in tumor malignancy, including proliferation, invasion, metastasis, and immune escape. Therefore, the development of new treatment methods that can adapt to the evolutionary characteristics of tumors has become an intense focus in current cancer treatment research. This paper explores the latest understanding of cancer evolution, focusing on how tumors use new antigens to shape their "new faces"; how immune system cells, such as cytotoxic T cells, regulatory T cells, macrophages, and natural killer cells, help tumors become "invisible", that is, immune escape; whether the diverse cancer-associated fibroblasts provide support and coordination for tumors; and whether it is possible to attack tumors in reverse. This paper discusses the limitations of targeted therapy driven by tumor evolution factors and explores future strategies and the potential of intelligent nanomedicines, including the systematic coordination of tumor evolution factors and adaptive methods, to meet this therapeutic challenge.

Advancing bone regeneration: Unveiling the potential of 3D cell models in the evaluation of bone regenerative materials.

Bone, a rigid yet regenerative tissue, has garnered extensive attention for its impressive healing abilities. Despite advancements in understanding bone repair and creating treatments for bone injuries, handling nonunions and large defects remains a major challenge in orthopedics. The rise of bone regenerative materials is transforming the approach to bone repair, offering innovative solutions for nonunions and significant defects, and thus reshaping orthopedic care. Evaluating these materials effectively is key to advancing bone tissue regeneration, especially in difficult healing scenarios, making it a critical research area. Traditional evaluation methods, including two-dimensional cell models and animal models, have limitations in predicting accurately. This has led to exploring alternative methods, like 3D cell models, which provide fresh perspectives for assessing bone materials' regenerative potential. This paper discusses various techniques for constructing 3D cell models, their pros and cons, and crucial factors to consider when using these models to evaluate bone regenerative materials. We also highlight the significance of 3D cell models in the in vitro assessments of these materials, discuss their current drawbacks and limitations, and suggest future research directions. STATEMENT OF SIGNIFICANCE: This work addresses the challenge of evaluating bone regenerative materials (BRMs) crucial for bone tissue engineering. It explores the emerging role of 3D cell models as superior alternatives to traditional methods for assessing these materials. By dissecting the construction, key factors of evaluating, advantages, limitations, and practical considerations of 3D cell models, the paper elucidates their significance in overcoming current evaluation method shortcomings. It highlights how these models offer a more physiologically relevant and ethically preferable platform for the precise assessment of BRMs. This contribution is particularly significant for "Acta Biomaterialia" readership, as it not only synthesizes current knowledge but also propels the discourse forward in the search for advanced solutions in bone tissue engineering and regeneration.

Shining a light on liver health: advancements in fluorescence-enhanced enzyme biosensors for early disease detection.

Early detection of liver diseases holds paramount importance in optimizing treatment outcomes and prognosis, thereby significantly enhancing the likelihood of recovery while mitigating the risk of progression to liver cancer. Liver diseases encompass a spectrum of conditions, each potentially manifesting distinct enzymatic profiles. Monitoring these enzymes in situ facilitates timely intervention and therapeutic management. In recent years, the field of biosensor technology has witnessed remarkable advancement, owing to strides in biomedicine and computational sciences. Biosensors have garnered widespread utility across medical and biological domains, spanning the detection of disease biomarkers, drug release tracking, ion imaging, and fluorescence imaging within living organisms. These applications have markedly enhanced imaging resolution and have the potential to refine disease diagnosis accuracy for clinicians. A pivotal aspect in the successful application of this technology lies in the construction of fluorescence probes adept at swiftly and selectively identifying target enzymes by amalgamating liver disease enzymes with fluorescence probe technology. However, research in this niche area remains relatively scarce. Building upon this foundational understanding, the present review delineates the utilization of biosensors in the early diagnosis of liver disease. Serving as a theoretical framework, this review envisages the development of high-performance biosensors tailored for the early detection of liver cancer. Furthermore, it offers insights into the potential of biosensor technology to progress and broaden its practical applications, thus contributing to the advancement of diagnostic methodologies in liver disease management.

Crosstalk among disulfidptosis-related lncRNAs in lung adenocarcinoma reveals a correlation with immune profile and clinical prognosis.

Disulfidptosis refers to a specific programmed cell death process characterized by the accumulation of disulfides. It has recently been reported in several cancers. However, the impact of disulfidptosis-related long non-coding RNAs (lncRNAs) on malignant tumors has remained largely unknown. In the present work, we screened prognostic disulfidptosis-related lncRNAs and studied their effects on lung adenocarcinoma. Relevant clinical data of lung adenocarcinoma cases were retrieved from The Cancer Genome Atlas (TCGA) database. RNA sequencing was used to identify differentially expressed disulfidptosis-related lncRNAs within lung adenocarcinoma. In addition, prognostic disulfidptosis-related lncRNAs were obtained through univariate Cox regression analysis. LASSO-COX was used to construct new disulfidptosis-related lncRNA signatures. Different statistical approaches were used to validate the practicability and accuracy of the disulfidptosis-related lncRNAs signatures. Furthermore, several bioinformatic approaches were used to study relevant heterogeneities in biological processes and pathways of diverse risk groups. Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was conducted to analyze the expression of disulfidptosis-related lncRNAs. Finally, seven disulfidptosis-related lncRNA signatures were identified in lung adenocarcinoma cells. The prognosis prediction model constructed efficiently predicted patient survival. Subgroup analysis revealed significant differences in immune cell proportion, including T follicular helper cells and M0 macrophages. In addition, in vitro experimental results demonstrated significant differences in disulfidptosis-related lncRNAs. Altogether, the six disulfidptosis-related lncRNA signatures could serve as a potential prognostic biomarker for lung adenocarcinoma. Furthermore, these can be used as a prediction model in individualized immunotherapy for lung adenocarcinoma.

Clinical advances in TNC delivery vectors and their conjugate agents.

Tenascin C (TNC), a glycoprotein that is abundant in the tumor extracellular matrix (ECM), is strongly overexpressed in tumor tissues but virtually undetectable in most normal tissues. Many TNC antibodies, peptides, aptamers, and nanobodies have been investigated as delivery vectors, including 20A1, α-A2, α-A3, α-IIIB, α-D, BC-2, BC-4 BC-8, 81C6, ch81C6, F16, FHK, Ft, Ft-NP, G11, G11-iRGD, GBI-10, 19H12, J1/TN1, J1/TN2, J1/TN3, J1/TN4, J1/TN5, NJT3, NJT4, NJT6, P12, PL1, PL3, R6N, SMART, ST2146, ST2485, TN11, TN12, TNFnA1A2-Fc, TNfnA1D-Fc, TNfnBD-Fc, TNFnCD-Fc, TNfnD6-Fc, TNfn78-Fc, TTA1, TTA1.1, and TTA1.2. In particular, BC-2, BC-4, 81C6, ch81C6, F16, FHK, G11, PL1, PL3, R6N, ST2146, TN11, and TN12 have been tested in human tissues. G11-iRGD and simultaneous multiple aptamers and arginine-glycine-aspartic acid (RGD) targeting (SMART) may be assessed in clinical trials because G11, iRGD and AS1411 (SMART components) are already in clinical trials. Many TNC-conjugate agents, including antibody-drug conjugates (ADCs), antibody fragment-drug conjugates (FDCs), immune-stimulating antibody conjugates (ISACs), and radionuclide-drug conjugates (RDCs), have been investigated in preclinical and clinical trials. RDCs investigated in clinical trials include 111In-DTPA-BC-2, 131I-BC-2, 131I-BC-4, 90Y-BC4, 131I81C6, 131I-ch81C6, 211At-ch81C6, F16124I, 131I-tenatumomab, ST2146biot, FDC 131I-F16S1PF(ab')2, and ISAC F16IL2. ADCs (including FHK-SSL-Nav, FHK-NB-DOX, Ft-NP-PTX, and F16*-MMAE) and ISACs (IL12-R6N and 125I-G11-IL2) may enter clinical trials because they contain components of marketed treatments or agents that were investigated in previous clinical studies. This comprehensive review presents historical perspectives on clinical advances in TNC-conjugate agents to provide timely information to facilitate tumor-targeting drug development using TNC.

Nanotechnology for brain tumor imaging and therapy based on π-conjugated materials: state-of-the-art advances and prospects.

In contemporary biomedical research, the development of nanotechnology has brought forth numerous possibilities for brain tumor imaging and therapy. Among these, π-conjugated materials have garnered significant attention as a special class of nanomaterials in brain tumor-related studies. With their excellent optical and electronic properties, π-conjugated materials can be tailored in structure and nature to facilitate applications in multimodal imaging, nano-drug delivery, photothermal therapy, and other related fields. This review focuses on presenting the cutting-edge advances and application prospects of π-conjugated materials in brain tumor imaging and therapeutic nanotechnology.

Application of FGD-BCEL loss function in segmenting temporal lobes on localized CT images for radiotherapy.

Objectives: The aim of this study was to find a new loss function to automatically segment temporal lobes on localized CT images for radiotherapy with more accuracy and a solution to dealing with the classification of class-imbalanced samples in temporal lobe segmentation. Methods: Localized CT images for radiotherapy of 70 patients with nasopharyngeal carcinoma were selected. Radiation oncologists sketched mask maps. The dataset was randomly divided into the training set (n = 49), the validation set (n = 7), and the test set (n = 14). The training set was expanded by rotation, flipping, zooming, and shearing, and the models were evaluated using Dice similarity coefficient (DSC), Jaccard similarity coefficient (JSC), positive predictive value (PPV), sensitivity (SE), and Hausdorff distance (HD). This study presented an improved loss function, focal generalized Dice-binary cross-entropy loss (FGD-BCEL), and compared it with four other loss functions, Dice loss (DL), generalized Dice loss (GDL), Tversky loss (TL), and focal Tversky loss (FTL), using the U-Net model framework. Results: With the U-Net model based on FGD-BCEL, the DSC, JSC, PPV, SE, and HD were 0.87 ± 0.11, 0.78 ± 0.11, 0.90 ± 0.10, 0.87 ± 0.13, and 4.11 ± 0.75, respectively. Except for the SE, all the other evaluation metric values of the temporal lobes segmented by the FGD-BCEL-based U-Net model were improved compared to the DL, GDL, TL, and FTL loss function-based U-Net models. Moreover, the FGD-BCEL-based U-Net model was morphologically more similar to the mask maps. The over- and under-segmentation was lessened, and it effectively segmented the tiny structures in the upper and lower poles of the temporal lobe with a limited number of samples. Conclusions: For the segmentation of the temporal lobe on localized CT images for radiotherapy, the U-Net model based on the FGD-BCEL can meet the basic clinical requirements and effectively reduce the over- and under-segmentation compared with the U-Net models based on the other four loss functions. However, there still exists some over- and under-segmentation in the results, and further improvement is needed.

An overview of current advances of PD-L1 targeting immuno-imaging in cancers.

The programmed death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) pathway plays a significant role in immune evasion. PD-1 or PD-L1 immune checkpoint inhibitors (ICIs) have become a standard treatment for multiple types of cancer. To date, PD-L1 has served as a biomarker for predicting the efficacy of ICIs in several cancers. The need to establish an effective detection method that could visualize PD-L1 expression and predict the efficacy of PD-1/PD-L1 ICIs has promoted a search for new imaging strategies. PD-L1-targeting immuno-imaging could provide a noninvasive, real-time, repeatable, dynamic, and quantitative assessment of the characteristics of all tumor lesions in individual patients. This study analyzed the existing evidence in the literature on PD-L1-based immuno-imaging (2015-2022). Original English-language articles were searched using PubMed and Google Scholar. Keywords, such as "PD-L1," "PET," "SPECT," "PET/CT," and "SPECT/CT," were used in various combinations. A total of nearly 50 preclinical and clinical studies of PD-L1-targeting immuno-imaging were selected, reviewed, and included in this study. Therefore, in this review, we conducted a study of the advances in PD-L1-targeting immuno-imaging for detecting the expression of PD-L1 and the efficacy of ICIs. We focused on the different types of PD-L1-targeting agents, including antibodies and small PD-L1-binding agents, and illustrated the strength and weakness of these probes. Furthermore, we summarized the trends in the development of PD-L1-targeting immuno-imaging, as well as the current challenges and future directions for clinical workflow.

Clinical outcomes of radioactive seed brachytherapy and microwave ablation in inoperable stage I non-small cell lung cancer.

This study assessed the efficacy and safety of radioactive iodine-125 seed ablation brachytherapy (RSABT) in comparison to microwave ablation therapy (MWAT) for treating inoperable stage I non-small cell lung cancer (NSCLC). We conducted a retrospective analysis of data from stage I NSCLC patients who underwent CT-guided RSABT or MWAT. The primary outcomes measured were progression-free survival (PFS), overall survival (OS), and the occurrence of adverse events. Of the patients included in the study, 71 underwent RSABT and 105 received MWAT. The median follow-up time for these groups was 47.4 months and 60 months, respectively. The PFS rates at 1-year, 3-year, and 5-year for the RSABT group were 87.3%, 72.6%, and 65.8%, while for the MWAT group, they were 89.5%, 69.3%, and 43.7%, respectively (P = 0.011). The OS rates at 1-year, 3-year, and 5-year for the RSABT group were 97.2%, 78.1%, and 66.1%, and for the MWAT group, they were 99%, 75.8%, and 55%, respectively (P = 0.112). Upon multivariate analysis, the treatment modality was identified as an independent predictor of PFS (P = 0.008). Additionally, both sex and T stage were found to be independent predictors of both PFS and OS (P < 0.05). Adverse events, such as pneumothorax, occurred in 50% of the MWAT group and 39% of the RSABT group (P = 0.313). The incidence of pleural effusion was 44% in the MWAT group compared to 14% in the RSABT group (P < 0.001). Needle bleeding was observed in 32% of the RSABT group and 5% of the MWAT group (P < 0.001). We conclude RSABT demonstrates promising efficacy and safety in the treatment of stage I NSCLC. However, further studies are essential to validate these preliminary findings.

Lung Transplantation for Pulmonary Arterial Hypertension: Optimized Referral and Listing Based on an Evolving Disease Concept.

Pulmonary hypertension (PH) was once a devastating and fatal disease entity, the outlook of which has been significantly improved by the continued progress of medical treatment algorithms. However, some patients still ultimately fail to achieve an adequate clinical response despite receiving maximal medical treatment. Historically, lung transplantation (LTx) has been the only effective therapeutic option that could lead to satisfactory outcomes and save these advanced patients' lives. However, patients with PH tend to have the highest mortality rates on the transplant waiting list; especially after comprehensive medical treatment, they continue to deteriorate very rapidly, eventually missing optimal transplantation windows. Balancing optimized medical treatment with the appropriate timing of referral and listing has been highly controversial in LTx for patients with PH. The 2021 consensus document for the selection of lung transplant candidates from the International Society for Heart and Lung Transplantation (ISHLT) updated the specific recommendations for the LTx referral and listing time for patients with PH based on objective risk stratification. Herein, we review the evolving PH-related concepts and highlight the optimization of LTx referral and listing for patients with PH, as well as their management on the waiting list.

The potential role and mechanism of circRNA/miRNA axis in cholesterol synthesis.

Cholesterol levels are an initiating risk factor for atherosclerosis. Many genes play a central role in cholesterol synthesis, including HMGCR, SQLE, HMGCS1, FDFT1, LSS, MVK, PMK, MVD, FDPS, CYP51, TM7SF2, LBR, MSMO1, NSDHL, HSD17B7, DHCR24, EBP, SC5D, DHCR7, IDI1/2. Especially, HMGCR, SQLE, FDFT1, LSS, FDPS, CYP51, and EBP are promising therapeutic targets for drug development due to many drugs have been approved and entered into clinical research by targeting these genes. However, new targets and drugs still need to be discovered. Interestingly, many small nucleic acid drugs and vaccines were approved for the market, including Inclisiran, Patisiran, Inotersen, Givosiran, Lumasiran, Nusinersen, Volanesorsen, Eteplirsen, Golodirsen, Viltolarsen, Casimersen, Elasomeran, Tozinameran. However, these agents are all linear RNA agents. Circular RNAs (circRNAs) may have longer half-lives, higher stability, lower immunogenicity, lower production costs, and higher delivery efficiency than these agents due to their covalently closed structures. CircRNA agents are developed by several companies, including Orna Therapeutics, Laronde, and CirCode, Therorna. Many studies have shown that circRNAs regulate cholesterol synthesis by regulating HMGCR, SQLE, HMGCS1, ACS, YWHAG, PTEN, DHCR24, SREBP-2, and PMK expression. MiRNAs are essential for circRNA-mediated cholesterol biosynthesis. Notable, the phase II trial for inhibiting miR-122 with nucleic acid drugs has been completed. Suppressing HMGCR, SQLE, and miR-122 with circRNA_ABCA1, circ-PRKCH, circEZH2, circRNA-SCAP, and circFOXO3 are the promising therapeutic target for drug development, specifically the circFOXO3. This review focuses on the role and mechanism of the circRNA/miRNA axis in cholesterol synthesis in the hope of providing knowledge to identify new targets.

Protection efficacy of the H1 and H3 bivalent virus-like particle vaccine against swine influenza virus infection.

Swine influenza (SI) is widely prevalent in pig herds worldwide, causing huge economic losses to the pig industry and public health risks. The traditional inactivated swine influenza virus (SIV) vaccines are produced in chicken embryos, and egg-adaptive substitutions that occur during production process can impact vaccine effectiveness. Thus, developing an SI vaccine that can decrease the dependence on chicken embryos with a high immunogenicity is urgently needed. In this study, the utility of insect cell-derived SIV H1 and H3 bivalent virus-like particle (VLP) vaccines containing HA and M1 proteins of Eurasian avian-like (EA) H1N1 SIV and recent human-like H3N2 SIV were assessed in piglets. Antibody levels were monitored, and the protection efficacy of the vaccine after viral challenge was evaluated and compared with the inactivated vaccine. Results show that piglets produced high hemagglutination inhibition (HI) titers of antibodies against H1 and H3 SIV after immunization with SIV VLP vaccine. The neutralizing antibody level was significantly higher in SIV VLP vaccine than in the inactivated vaccine at 6 weeks post vaccination (p < 0.05). Furthermore, piglets immunized with the SIV VLP vaccine were protected against the challenge of H1 and H3 SIV, displaying inhibition of viral replication in piglets, and reduced lung damage. These results show that SIV VLP vaccine has good application prospects, thus laying the foundation for further research and commercialization of SIV VLP vaccine.

VX-765 has a Protective Effect on Mice with Ovarian Injury Caused by Chemotherapy.

BACKGROUND: Malignant tumors continue to remain a main global public health issue. In the past 40 years, due to strides made in multi-disciplinary comprehensive treatment schemes for patients suffering from malignant tumors, especially chemotherapy schemes, the survival rate has been greatly improved in such patients. This group can be expected to maintain their fertility or have restored endocrine function following successful malignant tumor treatment. Therefore, focusing on the ovarian damage caused by chemotherapy in women of childbearing age is vital in order to protect their fertility and improve their quality of life. OBJECTIVE: This study attempted to evaluate whether VX-765 possesses an ovarian protective effect in ovarian injury induced by chemotherapy in the mice model. METHODS: Female C57BL/6J mice were administered with VX-765 gavage once a day for 21 consecutive days. Use of cyclophosphamide (Cy) began one week after the last gavage administration of VX- 765. Detailed classification of follicles at various levels was then quantified in each group. Immunohistochemistry and Western blot analysis were then used in order to analyze the expression of key proteins (FOXO3a, mTOR, RPS6 and AKT) as well as their phosphorylation of the PI3K / PTEN / AKT pathways in the ovary. The concentrations of AMH were measured by ELISA. RESULTS: The follicles at all levels of Cy treated mice were less than those of the normal group (P < 0.05). Meanwhile, mice treated with VX-765 prior to receiving Cy treatment had more primordial follicles (PMF) than mice treated with Cy alone (P < 0.05). In early growing follicles (EGF) and antral follicles (AF), no difference was observed among the experimental groups (P > 0.05), however, they were lower than those in the normal group (P < 0.05). In mice treated with continuous Cy, the total follicle number (TF) of mice combined with VX-765 (C-Cy-Vx765) was higher than that of mice without VX-765, and the TF of the two groups was lower than that of the normal group (P < 0.05). The value of PMF/TF in C-Cy-Vx765 group was significantly higher than that in the other three groups, while that of EGF/TF was significantly lower (P < 0.05). Immunohistochemical results showed that the phosphorylated forms of the main proteins of the PI3K / PTEN / AKT pathway were found to be more positive in Cy treated mice. The Western blot analysis showed that when Cy and VX-765 were cotreated, the increased levels of these phosphorylated proteins decreased compared with those treated with Cy alone. The AMH level of infancy Cy and VX-765 co-treated mice was higher than that of infancy normal mice (P < 0.05). After the mice grew to sexual maturity, the AMH level of Cy and VX- 765 co-treated mice was still higher than that of Cy treated mice (P < 0.05), and there was no significant difference with normal mice (P > 0.05). CONCLUSION: VX-765 can maintain the level of AMH and inhibit the recruitment of PMF, thus protecting mice from Cy induced gonadotropic toxicity. Accordingly, VX-765 may play a protective role in mice with ovarian injury caused by chemotherapy.

Current and future perspectives for Helicobacter pylori treatment and management: From antibiotics to probiotics.

Helicobacter pylori (H. pylori) is a Gram-negative anaerobic bacterium that colonizes the human stomach and is the leading cause of gastric diseases such as chronic gastritis and peptic ulcers, as well as the most definite and controllable risk factor for the development of gastric cancer. Currently, the regimen for H. pylori eradication has changed from triple to quadruple, the course of treatment has been extended, and the type and dose of antibiotics have been adjusted, with limited improvement in efficacy but gradually increasing side effects and repeated treatment failures in an increasing number of patients. In recent years, probiotics have become one of the most important tools for supporting intestinal health and immunity. Numerous in vitro studies, animal studies, and clinical observations have demonstrated that probiotics have the advantage of reducing side effects and increasing eradication rates in adjuvant anti-H. pylori therapy and are a valuable supplement to conventional therapy. However, many different types of probiotics are used as adjuncts against H. pylori, in various combinations, with different doses and timing, and the quality of clinical studies varies, making it difficult to standardize the results. In this paper, we focus on the risk, status, prevention, control, and treatment of H. pylori infection and review international consensus guidelines. We also summarize the available scientific evidence on using Limosilactobacillus reuteri (L. reuteri) as a critical probiotic for H. pylori treatment and discuss its clinical research and application from an evidence-based perspective.

The Impact of Late Follicular Phase Progesterone Elevation on Cumulative Live Birth Rate and Embryo Quality in 4072 Freeze-All Cycles.

Late follicular phase progesterone elevation during in vitro fertilization impedes embryo implantation. It is unclear whether late follicular phase progesterone elevation still has a negative effect on cumulative live births and embryo quality when a freeze-all strategy is adopted. Data from a total of 4072 patients were reviewed. All patients used the freeze-all strategy. Multivariate regression analyses were used to assess the association of progesterone levels with both cumulative live birth and embryo quality. There was no significant difference in the cumulative live birth rate between the groups with progesterone level <1.5 ng/mL and ≥1.5 ng/mL. The progesterone level was not associated with cumulative live birth and embryo quality.

ALT-803 in the treatment of non-muscle-invasive bladder cancer: Preclinical and clinical evidence and translational potential.

Bladder cancer (BCa) is one of the most common malignant tumors that cause death. Approximately 75%-85% of BCa develop into non-muscle-invasive bladder cancer (NMIBC). Bacillus Calmette-Guérin (BCG) is the gold standard for avoiding cystectomy in the treatment of NMIBC. Unfortunately, up to 30% of patients do not respond to BCG treatment, and up to 70% of BCG responders relapse. The United States Food and Drug Administration (FDA) approved valrubicin (1998) and pembrolizumab (2020) for the treatment of BCG-unresponsive (BCGu) NMBIC. However, the complete remission rate for valrubicin and pembrolizumab was only 16% and 40.6%, respectively. ALT-803 (N-803) is an IL-15 superagonist and reduces tumor burden by promoting the proliferation and activation of NK cells and CD8+ T cells. The FDA received (23 May 2022) and accepted to review (28 July 2022) the marketing submission of ALT-803 plus BCG for the treatment of BCGu NMIBC. However, the FDA previously rejected the application for oportuzumab monatox (OM) due to a lack of data comparing it with pembrolizumab on August 20, 2021. Interestingly, the clinical efficacy and safety of ALT-803 were higher than that of pembrolizumab and OM, suggesting that ALT-803 may be approved by FDA. This review aims to further knowledge of the preclinical and clinical evidence of ALT-803 in the treatment of NMIBC and discuss its translational potential.