Natural orifice specimen extraction surgery versus small-incision assisted laparoscopic radical right hemicolectomy.

Conventional laparoscopic-assisted right hemicolectomy requires a small abdominal incision to extract the specimen, which becomes an important source of postoperative complications and impairs perioperative experience. Transvaginal natural orifice specimen extraction surgery (NOSES VIIIA) avoids this small incision by extracting the specimen through the vagina. Here we describe the design of a multicenter, open-label, parallel, noninferior, phase III randomized controlled trial (NCT05495048). The aim of this study is to confirm that the NOSES VIIIA procedure is not inferior to small-incision assisted right hemicolectomy in long-term oncological efficacy. A total of 352 female patients with right colon adenocarcinoma/high-grade intraepithelial neoplasia will be randomly assigned to the NOSES VIIIA arm and the small-incision arm in a 1:1 ratio. The primary end point of this trial is 3 year disease-free survival. Clinical Trial Registration: NCT05495048 (ClinicalTrials.gov).

[Application of Magnetization-prepared True Fast Imaging with Steady-state Precession Sequence in Brain Tumor Enhancement].

Objective To evaluate the application of two-dimensional magnetization-prepared true fast imaging with steady-state precession(2D-MP-TrueFISP)sequence in brain tumor enhancement.Methods In this study,60 cases of brain tumor patients who underwent enhanced magnetic resonance imaging of brain were scanned with 2D-MP-TrueFISP/two-dimensional spoiled gradient-recalled echo(2D-SPGR)before and after enhancement.The scores of lesions on the images of 2D-MP-TrueFISP/2D-SPGR were compared.At the same level of 2D-SPGE and 2D-MP-TrueFISP,the signal intensities(SIs)of lesions,white matter,and cerebrospinal fluid were measured before and after enhancement,and the contrast ratios(CRs)of lesions were calculated.The CRs before and after 2D-SPGR/2D-MP-TrueFISP enhancement and those between 2D-SPGR and 2D-MP-TrueFISP after enhancement were compared.Results The scores of lesions after 2D-MP-TrueFISP/2D-SPGR T1WI enhancement were 9.0(9.0,9.0)and 7.0(6.0,7.0),respectively,with significant difference(Z=-6.86,P=0.00).CRs showed significant difference before and after enhancement with 2D-SPGR and 2D-MP-TrueFISP(all P<0.01).The CRs of lesion compared with white matter and cerebrospinal fluid(1.58±0.46 and 8.50±2.47,respectively)after 2D-MP-TrueFISP enhancement were significantly higher than those[0.57±0.29(t=-17.38,P=0.00)and 2.64±0.85(t=-19.71,P=0.00),respectively]after 2D-SPGR enhancement.Conclusion Compared with 2D-SPGR,2D-MP-TrueFISP demonstrated improved enhancement and uniformity as well as clear boundary and display of edema around the lesion.

Glycosylation and Its Role in Immune Checkpoint Proteins: From Molecular Mechanisms to Clinical Implications.

Immune checkpoint proteins have become recent research hotspots for their vital role in maintaining peripheral immune tolerance and suppressing immune response function in a wide range of tumors. Therefore, investigating the immunomodulatory functions of immune checkpoints and their therapeutic potential for clinical use is of paramount importance. The immune checkpoint blockade (ICB) is an important component of cancer immunotherapy, as it targets inhibitory immune signaling transduction with antagonistic antibodies to restore the host immune response. Anti-programmed cell death-1 (PD-1) and anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) monoclonal antibodies are two main types of widely used ICBs that drastically improve the survival and prognosis of many patients with cancer. Nevertheless, the response rate of most cancer types remains relatively low due to the drug resistance of ICBs, which calls for an in-depth exploration to improve their efficacy. Accumulating evidence suggests that immune checkpoint proteins are glycosylated in forms of N-glycosylation, core fucosylation, or sialylation, which affect multiple biological functions of proteins such as protein biosynthesis, stability, and interaction. In this review, we give a brief introduction to several immune checkpoints and summarize primary molecular mechanisms that modulate protein stability and immunosuppressive function. In addition, newly developed methods targeting glycosylation on immune checkpoints for detection used to stratify patients, as well as small-molecule agents disrupting receptor-ligand interactions to circumvent drug resistance of traditional ICBs, in order to increase the clinical efficacy of immunotherapy strategies of patients with cancer, are also included to provide new insights into scientific research and clinical treatments.

Synthesis of high-crystallinity Zeolite A from rare earth tailings: Investigating adsorption performance on typical pollutants in rare earth mines.

The ecological restoration of rare earth mines and the management of rare earth tailings have consistently posed global challenges, constraining the development of the rare earth industry. In this study, Zeolite A is efficiently prepared from the tailings of an ion-type rare earth mine in the southern Jiangxi Province of China. The resulting Zeolite A boasts exceptional qualities, including high crystallinity, a substantial specific surface area, and robust thermal stability. The optimum conditions for Zeolite synthesis are experimental determination and the adsorption properties of Zeolite A for typical pollutants (Cd2+, Cu2+, NH4+, PO43- and F-) in rare earth mines. The synthesised Zeolite A material is found to have strong adsorption properties. The adsorption mechanism is mainly cation exchange, and the priority of adsorption of pollutants is Cu2+> Cd2+ > NH4+ > PO43- > F-. Notably, the sodium Zeolite A material synthesized at room temperature can be effectively recycled multiple times. In summary, we propose a method to synthesise low cost and high adsorption zeolites using rare earth tailings. This will facilitate the reduction of rare earth tailings and the rehabilitation of rare earth mines. Our method has great potential as a rehabilitation technology for rare earth mines.

Revolutionizing sphincter preservation in ultra-low rectal cancer: exploring the potential of transanal endoscopic intersphincteric resection (taE-ISR): a propensity score-matched cohort study.

BACKGROUND: With the optimization of neoadjuvant treatment regimens, the indications for intersphincteric resection (ISR) have expanded. However, limitations such as unclear surgical field, impaired anal function, and failure of anal preservation still exist. Transanal total mesorectal excision can complement the drawbacks of ISR. Therefore, this study combined these two techniques and proposed transanal endoscopic intersphincteric resection (taE-ISR), aiming to explore the value of this novel technique in anal preservation for ultra-low rectal cancer. MATERIAL AND METHODS: Four high-volume centres were involved. After 1:1 propensity score-matching, patients with ultra-low rectal cancer underwent taE-ISR ( n =90) or ISR ( n =90) were included. Baseline characteristics, perioperative outcomes, pathological results, and follow-up were compared between the two groups. A nomogram model was established to assess the potential risks of anal preservation. RESULTS: The incidence of adjacent organ injury (0.0% vs. 5.6%, P =0.059), positive distal resection margin (1.1% vs. 8.9%, P =0.034), and incomplete specimen (2.2% vs. 13.3%, P =0.012) were lower in taE-ISR group. Moreover, the anal preservation rate was significantly higher in taE-ISR group (97.8% vs. 82.2%, P =0.001). Patients in the taE-ISR group showed a better disease-free survival ( P =0.044) and lower cumulative recurrence ( P =0.022) compared to the ISR group. Surgery procedure, tumour distance, and adjacent organ injury were factors influencing anal preservation in patients with ultra-low rectal cancer. CONCLUSION: taE-ISR technique was safe, feasible, and improved surgical quality, anal preservation rate and survival outcomes in ultra-low rectal cancer patients. It held significant clinical value and showed promising application prospects for anal preservation.

Role of phosphite in the environmental phosphorus cycle.

In modern geochemistry, phosphorus (P) is considered synonymous with phosphate (Pi) because Pi controls the growth of organisms as a limiting nutrient in many ecosystems. The researchers therefore realised that a complete P cycle is essential. Limited by thermodynamic barriers, P was long believed to be incapable of redox reactions, and the role of the redox cycle of reduced P in the global P cycling system was thus not ascertained. Nevertheless, the phosphite (Phi) form of P is widely present in various environments and participates in the global P redox cycle. Herein, global quantitative evidences of Phi are enumerated and the early origin and modern biotic/abiotic sources of Phi are elaborated. Further, the Phi-based redox pathway for P reduction is analysed and global multienvironmental Phi redox cycle processes are proposed on the basis of this pathway. The possible role of Phi in controlling algae in eutrophic lakes and its ecological benefits to plants are proposed. In this manner, the important role of Phi in the P redox cycle and global P cycle is systematically and comprehensively identified and confirmed. This work will provide scientific guidance for the future production and use of Phi products and arouse attention and interest on clarifying the role of Phi in the environmental phosphorus cycle.

Integrative analysis revealed that distinct cuprotosis patterns reshaped tumor microenvironment and responses to immunotherapy of colorectal cancer.

Background: Cuprotosis is a novel form of programmed cell death that involves direct targeting of key enzymes in the tricarboxylic acid (TCA) cycle by excess copper and may result in mitochondrial metabolic dysfunction. However, whether cuprotosis may mediate the tumor microenvironment (TME) and immune regulation in colorectal cancer (CRC) remains unclear. Methods: Ten cuprotosis-related genes were selected and unsupervised consensus clustering was performed to identify the cuprotosis patterns and the correlated TME characteristics. Using principal component analysis, a COPsig score was established to quantify cuprotosis patterns in individual patients. The top 9 most important cuprotosis signature genes were analyzed using single-cell transcriptome data. Results: Three distinct cuprotosis patterns were identified. The TME cell infiltration characteristics of three patterns were associated with immune-excluded, immune-desert, and immune-inflamed phenotype, respectively. Based on individual cuprotosis patterns, patients were assigned into high and low COPsig score groups. Patients with a higher COPsig score were characterized by longer overall survival time, lower immune cell as well as stromal infiltration, and greater tumor mutational burden. Moreover, further analysis demonstrated that CRC patients with a higher COPsig score were more likely to respond to immune checkpoint inhibitors and 5-fluorouracil chemotherapy. Single-cell transcriptome analysis indicated that cuprotosis signature genes recruited tumor-associated macrophages to TME through the regulation of TCA and the metabolism of glutamine and fatty acid, thus influencing the prognosis of CRC patients. Conclusion: This study indicated that distinct cuprotosis patterns laid a solid foundation to the explanation of heterogeneity and complexity of individual TME, thus guiding more effective immunotherapy as well as adjuvant chemotherapy strategies.

Modulation of soy protein isolate gel properties by a novel "two-step" gelation process: Effects of pre-aggregation with different divalent sulfates.

A novel pre-aggregation process prior to gelation was applied to modulate the aggregation and gelation pathway of soy protein isolate (SPI). SPI dispersions were pre-aggregated with CaSO4, MgSO4 or ZnSO4 at 0-15 mM and then gelled by adding CaSO4 up to a final salt concentration of 35 mM. Compared with the sample without pre-aggregation, the storage modulus of SPI gels pre-aggregated with 10 mM CaSO4, 10 mM MgSO4, and 2.5 mM ZnSO4 were increased by 50.5%, 35.7%, and 63.6%, respectively. The fracture stress, texture profile analysis parameters, and water holding capacity were markedly improved by an appropriate level of pre-aggregation. To a certain extent, pre-aggregation could promote the formation of uniform structure with thicker strands, whereas over-aggregation resulted in a coarser network, which was correlated with the volume-mean diameter (D4,3) of pre-aggregated SPI particles. The results are of great value for further understanding of gelation mechanism of proteins.

Heat-induced structural changes in fish muscle collagen related to texture development in fish balls: Using eel ball as a study model.

In order to elucidate the substantial effect and underlying mechanism of endogenous collagen on the texture development of fish balls, the structural and gelling properties of eel muscle collagen (EMC) under different heat treatments, as well as their effects on texture of eel ball, were investigated. EMC resulted in significant improvement of eel ball texture via gelling ability, filler effect, and interaction with starch. Under mild heating below 90°C for 30 min, the structural and physicochemical changes of EMC varied gradually, resulting in improved storage modulus of starch-containing myofibrillar gel, a mimic of eel ball. However, overheating (100°C, 30 min) induced EMC degradation and significantly decreased the gel formation and the improvements in textural properties. Supplementation of EMC to eel balls significantly improved its gel strength, springiness, cohesiveness, and chewiness, as well as uniformity and tightness of the microstructure. These results suggest the texture development of eel ball can be regulated by heat-induced structural changes, as well as structure-function relationship of collagen, compared with previous studies on myofibrillar proteins and exogenous gelatin; and they may provide texture-related insights to the quality control of fish balls and diverse heat-treated products of surimi containing collagen.

A potent neutralizing and protective antibody against a conserved continuous epitope on HSV glycoprotein D.

Infections caused by herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) remain a serious global health issue, and the medical countermeasures available thus far are limited. Virus-neutralizing monoclonal antibodies (NAbs) are crucial tools for studying host-virus interactions and designing effective vaccines, and the discovery and development of these NAbs could be one approach to treat or prevent HSV infection. Here, we report the isolation of five HSV NAbs from mice immunized with both HSV-1 and HSV-2. Among these were two antibodies that potently cross-neutralized both HSV-1 and HSV-2 with the 50% virus-inhibitory concentrations (IC50) below 200 ng/ml, one of which (4A3) exhibited high potency against HSV-2, with an IC50 of 59.88 ng/ml. 4A3 neutralized HSV at the prebinding stage and prevented HSV infection and cell-to-cell spread. Significantly, administration of 4A3 completely prevented weight loss and improved survival of mice challenged with a lethal dose of HSV-2. Using structure-guided molecular modeling combined with alanine-scanning mutagenesis, we observed that 4A3 bound to a highly conserved continuous epitope (residues 216 to 220) within the receptor-binding domain of glycoprotein D (gD) that is essential for viral infection and the triggering of membrane fusion. Our results provide guidance for developing NAb drugs and vaccines against HSV.

Oncolytic virus expressing PD-1 inhibitors activates a collaborative intratumoral immune response to control tumor and synergizes with CTLA-4 or TIM-3 blockade.

BACKGROUND: Oncolytic viruses (OVs) are capable to inflame the tumor microenvironment (TME) and elicit infiltrating tumor-specific T cell responses. However, OV treatment negatively alters the cancer-immune set point in tumors to attenuate the antitumor immune response, which suggests the necessity of dissecting the immune landscape of the virus-treated tumors and developing novel strategies to maximize the potential of OVs. The aim of this study is to investigate the effect of the single-chain variable fragment (scFv)-armed OVs targeting PD-1 on the TME, and ultimately overcome localized immunosuppression to sensitize tumors to immunotherapies. METHODS: A tumor-selective oncolytic herpes simplex virus vector was engineered to encode a humanized scFv against human PD-1 (hPD-1scFv) (YST-OVH). The antitumor efficacy of YST-OVH was explored in multiple therapeutic mouse models. The neurotoxicity and safety of YST-OVH were evaluated in nonhuman primates. The precise dynamics in the TME involved in YST-OVH treatment were dissected using cytometry by time-of-flight (CyTOF). RESULTS: The identified hPD-1scFv showed superior T-cell activating activity. Localized delivery of hPD-1scFv by YST-OVH promotes systemic antitumor immunity in humanized PD-1 mouse models of established cancer. Immune profiling of tumors using CyTOF revealed the enhanced antitumor effect of YST-OVH, which largely relied on CD8+ T cell activity by augmenting the tumor infiltration of effector CD8+ T cells and establishment of memory CD8+ T cells and reducing associated CD8+ T cell exhaustion. Furthermore, YST-OVH treatment modified the cancer-immune set point of tumors coupled to coexpression of CTLA-4 and TIM-3 on exhausted CD8+ T cells and high levels of CTLA-4+ Treg cells. A combination approach incorporating anti-CTLA-4 or anti-TIM-3 further improved efficacy by increasing tumor immunogenicity and activating antitumor adaptive immune responses. Moreover, this therapeutic strategy showed no neurotoxicity and was well tolerated in nonhuman primates. The benefit of intratumoral hPD-1scFv expression was also observed in humanized mice bearing human cancer cells. CONCLUSION: Localized delivery of PD-1 inhibitors by engineered YST-OVH was a highly effective and safe strategy for cancer immunotherapy. YST-OVH also synergized with CTLA-4 or TIM-3 blockade to enhance the immune response to cancer. These data provide a strong rationale for further clinical evaluation of this novel therapeutic approach.