Analysis of use of different rFSHs during IVF/ICSI-assisted conception in elderly population and effect of double trigger on clinical outcomes.

OBJECTIVE: To compare the number of oocytes retrieved and clinical outcomes of ovulation induction in an older population treated with in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) (IVF/ICSI) using different rFSH options and the effectiveness of antagonist treatment to induce ovulation using gonadotropin-releasing hormone agonists (GnRH-a) in combination with an human chorionic gonadotropin (HCG) trigger. METHODS: A total of 132 fresh cycles were selected for this study, which were treated with IVF/ICSI in our hospital from March 2022 to December 2022. Observations were made according to different subgroups and the effects of different triggering methods on the number of oocytes obtained, embryo quality, and clinical outcomes. RESULTS: The initial gonadotropin (Gn) dose, the number of oocytes, and the number of MII oocytes were higher in group A than in group B (p < .05), and the clinical pregnancy rate was 29.41% in group A. Group B had a clinical pregnancy rate of 27.5%. The double-trigger group was superior to the HCG-trigger group in terms of the number of 2PN, the number of viable embryos, and the number of high-quality embryos (p < .05). The use of a double-trigger regimen (OR = 0.667, 95%CI (0.375, 1.706), p = .024) was a protective factor for the clinical pregnancy rate, whereas AFC (OR = 0.925, 95%CI (0.867, 0.986), p = .017) was an independent factor for the clinical pregnancy rate. CONCLUSIONS: The use of a dual-trigger regimen of GnRH-a in combination with HCG using an appropriate antagonist improves pregnancy outcomes in fresh embryo transfer cycles in older patients.

KIr4O8 Nanowires with Rich Hydroxyl Promote Oxygen Evolution Reaction in Proton Exchange Membrane Water Electrolyzer.

The sluggish kinetics for anodic oxygen evolution reaction (OER) and insufficient catalytic performance over the corresponding Ir-based catalysts are still enormous challenges in proton exchange membrane water electrolyzer (PEMWE). Herein, it is reported that KIr4O8 nanowires anode catalyst with more exposed active sites and rich hydroxyl achieves a current density of 1.0 A cm-2 at 1.68 V and possesses excellent catalytic stability with 1230 h in PEMWE. Combining in situ Raman spectroscopy and differential electrochemical mass spectroscopy results, the modified adsorbate evolution mechanism is proposed, wherein the rich hydroxyl in the inherent structure of KIr4O8 nanowires directly participates in the catalytic process for favoring the OER. Density functional theory calculation results further suggest that the enhanced proximity between Ir (d) and O (p) band center in KIr4O8 can strengthen the covalence of Ir-O, facilitate the electron transfer between adsorbents and active sites, and decrease the energy barrier of rate-determining step from OH* to O* during the OER.

Association of SGLT2i vs DPP4i With Pneumonia, COVID-19, and Other Adverse Respiratory Events in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.

OBJECTIVE: Our aim in this study was to systematically assess the association of sodium-glucose cotransporter-2 inhibitors (SGLT2i) vs dipeptidyl peptidase-4 inhibitors (DPP4i) with pneumonia, COVID-19, and adverse respiratory events in patients with type 2 diabetes mellitus (DM). METHODS: PubMed, Embase, and Cochrane Library databases were retrieved to include studies on DM patients receiving SGLT2i (exposure group) or DPP4i (control group). Stata version 15.0 statistical software was used for the meta-analysis. RESULTS: Ten studies were included, all 10 of which were used for the qualitative review and 7 for the meta-analysis. According to the meta-analysis, patients receiving SGLT2i had a lower incidence of pneumonia (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.51 to 0.74) and pneumonia risk (OR 0.63, 95% CI 0.60 to 0.68, p=0.000) compared with those receiving DPP4i. The same situation was seen for mortality for pneumonia (OR 0.49, 95% CI 0.39 to 0.60) and pneumonia mortality risk (OR 0.47, 95% CI 0.42 to 0.51). There was lower mortality due to COVID-19 (OR 0.31, 95% CI 0.28 to 0.34) and a lower hospitalization rate (OR 0.61, 95% CI 0.56 to 0.68, p=0.000) and incidence of mechanical ventilation (OR 0.69, 95% CI 0.58 to 0.83, p=0.000) due to COVID-19 in patients with type 2 DM receiving SGLT2i. Qualitative analysis results show that SGLT2i was associated with a lower incidence of COVID-19, lower risk of obstructive airway disease events, and lower hospitalization rate of health-care-associated pneumonia than DPP4i. CONCLUSION: In patients with type 2 DM, SGLT2i are associated with a lower risk of pneumonia, COVID-19, and mortality than DPP4i.

YWHAG promotes colorectal cancer progression by regulating the CTTN-Wnt/ß-catenin signaling axis.

Colorectal cancer (CRC) ranks as the third most prevalent cancer type globally. Nevertheless, the fundamental mechanisms driving CRC progression remain ambiguous, and the prognosis for the majority of patients diagnosed at an advanced stage is dismal. YWHA/14-3-3 proteins serve as central nodes in several signaling pathways and are closely related to tumorigenesis and progression. However, their exact roles in CRC are still poorly elucidated. In this study, we revealed that YWHAG was the most significantly upregulated member of the YWHA/14-3-3 family in CRC tissues and was associated with a poor prognosis. Subsequent phenotypic experiments showed that YWHAG promoted the proliferation, migration, and invasion of CRC cells. Mechanistically, RNA-seq data showed that multiple signaling pathways, including Wnt and epithelial-mesenchymal transition, were potentially regulated by YWHAG. CTTN was identified as a YWHAG-associated protein, and mediated its tumor-promoting functions by activating the Wnt/ß-catenin signaling in CRC cells. In summary, our data indicate that YWHAG facilitates the proliferation, migration, and invasion of CRC cells by modulating the CTTN-Wnt/ß-catenin signaling pathway, which offers a novel perspective for the treatment of CRC.

Pros and Cons in Various Immobilization Techniques and Carriers for Enzymes.

In recent years, enzyme immobilization technology has been developed, and studies on immobilized enzyme materials have become very prominent. With the immobilization technique, enzymes and compatible carrier materials are combined or enzyme crystals/aggregates are used in a carrier-free fashion, by physical, chemical, or biochemical methods. As a kind of biocatalyst, immobilized enzymes can catalyze certain chemical reactions with high selectivity and high efficiency under relatively mild reaction conditions and eliminate pollution to the environment. Considering the current status and applications of immobilized enzyme technology and materials emerging in the last 5 years, this mini-review introduces the advantages and disadvantages of various enzyme immobilization techniques with carriers as well as the pros and cons of different materials for immobilization. The future prospects of immobilization technology and carrier materials are outlined, aiming to provide a reference for further research and applications of sustainable technology.

Metabolism-Triggered Plasmonic Nanosensor for Bacterial Detection and Antimicrobial Susceptibility Testing of Clinical Isolates.

Antimicrobial resistance (AMR) is predicted to become the leading cause of death worldwide in the coming decades. Rapid and on-site antibiotic susceptibility testing (AST) is crucial for guiding appropriate antibiotic choices to combat AMR. With this in mind, we have designed a simple and efficient plasmonic nanosensor consisting of Cu2+ and cysteine-modified AuNP (Au/Cys) that utilizes the metabolic activity of bacteria toward Cu2+ for bacterial detection and AST. When Cu2+ is present, it induces the aggregation of Au/Cys. However, in the presence of bacteria, Cu2+ is metabolized to varying extents, resulting in distinct levels of aggregation. Moreover, the metabolic activity of bacteria can be influenced by their antibiotic susceptibility, allowing us to differentiate between susceptible and resistant strains through direct color changes from the Cu2+-Au/Cys platform over approximately 3 h. These color changes can be easily detected using naked-eye observation, smartphone analysis, or absorption readout. We have validated the platform using four clinical isolates and six types of antibiotics, demonstrating a clinical sensitivity and specificity of 95.8%. Given its simplicity, low cost, high speed, and high accuracy, the plasmonic nanosensor holds great potential for point-of-care detection of antibiotic susceptibility across various settings.

Sulfurized NiFe2 O4 Electrocatalyst with In Situ Formed Fe-NiOOH Nanoparticles to Realize Industrial-Level Oxygen Evolution.

Constructing composite catalysts with refined geometric control and optimal electronic structure provides a promising route to enhance electrocatalytic performance toward the oxygen evolution reaction (OER). Herein, a composite catalyst is prepared with multiple components using chemical vapour deposition method to transform crystalline NiFe2 O4 into crystalline NiFe2 O4 @amorphous S-NiFe2 O4 with core-shell structure (C-NiFe2 O4 @A-S-NiFe2 O4 ), and Fe-NiOOH nanoparticles are subsequently in situ generated on its surface during the process of electrocatalytic OER. The C-NiFe2 O4 @A-S-NiFe2 O4 catalyst exhibits a low overpotential of 275 mV while possessing an excellent stability for 500 h at 10 mA cm-2 . The anion exchange membrane water electrolyzer with C-NiFe2 O4 @A-S-NiFe2 O4 anode catalyst obtains a current density of 4270 mA cm- 2 at 2.0 V. Further, in situ Raman spectroscopy result demonstrates that in situ generated Fe-NiOOH nanoparticles are revealed to act as the catalytic active phase for catalyzing the OER. Besides, introducing A-S-NiFe2 O4 in C-NiFe2 O4 @A-S-NiFe2 O4 facilitates the formation of Fe-NiOOH nanoparticles with high-valency Ni, thus increasing the proportion of lattice oxygen-participated OER. This work not only provides an alternative strategy for the design of high-performance catalysts, but also lays a foundation for the exploration of catalytic mechanisms.

Causal Relationship between Gut Microbiota and Gout: A Two-Sample Mendelian Randomization Study.

Gout is a form of prevalent and painful inflammatory arthritis characterized by elevated serum urate (SUA) levels. The gut microbiota (GM) is believed to influence the development of gout and SUA levels. Our study aimed to explore the causal relationship between GM composition and gout, as well as SUA levels, utilizing a two-sample Mendelian Randomization (MR) approach. A total of 196 GM taxa from five levels were available for analysis. We identified five taxa associated with SUA levels and 10 taxa associated with gout. In reverse MR analysis, we discovered that gout affected the composition of five GM taxa, while SUA levels influenced the composition of 30 GM taxa. Combining existing research, our study unveiled a potential negative feedback loop between phylum Actinobacteria and SUA levels, establishing connections with gout. We also proposed two novel associations connecting GM taxa (genus Faecalibacterium and genus Prevotella9), SUA levels, and gout. These findings provide compelling evidence of causal relationships between specific GM taxa with SUA levels and gout, contributing valuable insights for the treatment of gout.

Halogen-regulating induced reversible high-temperature dielectric and thermal transitions in novel layered organic-inorganic hybrid semiconducting crystals.

Organic-inorganic hybrid metal halides for high-temperature phase transition have become increasingly popular owing to their wide operating temperature range in practical applications, e.g., energy storage, permittivity switches and opto-electronic devices. This paper describes the subtle assembly of two new hybrid perovskite crystals, [Cl-C6H4-(CH2)2NH3]2CdX4 (X = Br 1; Cl 2), undergoing high-T reversible phase transformations around 335 K/356 K. Differential scanning calorimetry (DSC), differential thermal analysis (DTA) and VT PXRD tests uncover their reversible first-order phase transition behaviors. Furthermore, the compounds exhibit switchable dielectricity near T, making them potential dielectric switching materials. Hirshfeld surface analysis well discloses a distinct difference in hydrogen-bonding interaction between 1 and 2. UV spectra and computational analysis demonstrate that the compounds are a type of direct-band-gap semiconductor. This research will contribute an effective approach to the structure and development of multifunctional molecular hybrid crystals.

Excellent Switchable Properties, Broad-Band Emission, Ferroelectricity, and High Tc in a Two-Dimensional Hybrid Perovskite: (4,4-DCA)2PbBr4 Exploited by H/F Substitution.

Switchable materials have gained significant attention due to their potential applications in data storage, sensors, and switching devices. Two-dimensional (2D) hybrid perovskites have demonstrated promising prospects for designing switchable materials, where the dynamic motion of the organic components coupled with the distortion of the inorganic framework provides the driving force for triggering multifunctional switchable properties. Herein, through the H/F substitution strategy, we report a polar 2D hybrid lead-based perovskite, (4,4-DCA)2PbBr4 (4,4-DCA = 4,4-difluorocyclohexylammonium) (1), which exhibits dual-stable behavior in a dielectric and second harmonic generation (SHG) response during the reversible phase transition process near the high Curie temperature Tc ∼ 409 K. The phase transition temperature is significantly increased by 41 K compared to the corresponding non-fluorinated (CHA)2PbBr4 (CHA = cyclohexylammonium). Remarkably, the material shows rare broad-band yellow emission under UV excitation, attributed to the induction of self-trapped exciton emission by the distortion of the [PbBr6]4- octahedra, as confirmed by the first-principles analysis. 1 also exhibited ferroelectricity with a saturation polarization value and a small coercive field. This study provides a new insight into the modification of multifunctional switchable materials through the H/F substitution strategy.

Description of a new nematode species, Chromadorinacommunis sp. nov. (Nematoda, Chromadoridae), from Changdao Island, China and phylogenetic analysis of Chromadorida based on small subunit rRNA gene sequences.

Chromadorinacommunissp. nov. is described from Changdao Island at the confluence of the Yellow and the Bohai seas. The new species is characterized by its medium-sized body; finely striated cuticle with homogeneous punctations; absence of ocelli; buccal cavity with three equal-sized, solid teeth; four cephalic setae; oval amphidial fovea which is positioned between cephalic setae; curved spicules with tapered distal ends; simple, boat-shaped gubernaculums; five or six cup-shaped precloacal supplements; and conical tail with a very short spinneret. A phylogenetic analysis of small subunit rRNA gene sequences using maximum-likelihood and Bayesin inference confirmed the taxonomic position of Chromadorinacommunissp. nov. within Chromadorinae. Tree topology in Chromadorida shows six morphological families clustered into a monophyletic clade and verifies the taxonomic position of the family Neotonchidae based on morphological and molecular analysis.

Occupational low back pain prevention capacity of nurses in China: A multicenter cross-sectional study.

Introduction: Nurses have a high prevalence of occupational low back pain, especially since the outbreak of the COVID-19 pandemic, which has increased the nurses' workloads. It has brought a huge burden on nurses and their professional development. Nurses' occupational low back pain prevention capacity is the logical starting point and core of interventions to prevent its occurrence. To date, there is no study investigating it with a scientific scale. Therefore, a multicenter cross-sectional study was conducted to explore the current status of nurses' capacity in occupational low back pain prevention and its influencing factors in China. Methods: Using a two-stage, purposive and convenience mixed sampling method, 1331 nurses from 8 hospitals across 5 provinces (Hubei, Zhejiang, Shandong, Henan, and Sichuan) in the southern, western, northern, and central areas of mainland China were involved in this study. The demographic questionnaire and occupational low back pain prevention behavior questionnaire were used for data collection. The descriptive analysis, univariate analysis, and multiple stepwise linear regression were used for data analysis. Results: The results showed that the occupational low back pain prevention behavior questionnaire score was 89.00 (80.00, 103.00) [M (Q1, Q3)], which indicated that nurses' ability was at a moderate level. Participation in prevention training before, perceived stress at work, and working hours per week were predictors for nurses' occupational low back pain prevention capacity. Discussion: To improve nurses' prevention ability, nursing managers should organize various training programs, strengthen regulations to reduce nurses' workload and stress, provide a healthy workplace, and offer incentives to motivate nurses.

Advanced polymer hydrogels that promote diabetic ulcer healing: mechanisms, classifications, and medical applications.

Diabetic ulcers (DUs) are one of the most serious complications of diabetes mellitus. The application of a functional dressing is a crucial step in DU treatment and is associated with the patient's recovery and prognosis. However, traditional dressings with a simple structure and a single function cannot meet clinical requirements. Therefore, researchers have turned their attention to advanced polymer dressings and hydrogels to solve the therapeutic bottleneck of DU treatment. Hydrogels are a class of gels with a three-dimensional network structure that have good moisturizing properties and permeability and promote autolytic debridement and material exchange. Moreover, hydrogels mimic the natural environment of the extracellular matrix, providing suitable surroundings for cell proliferation. Thus, hydrogels with different mechanical strengths and biological properties have been extensively explored as DU dressing platforms. In this review, we define different types of hydrogels and elaborate the mechanisms by which they repair DUs. Moreover, we summarize the pathological process of DUs and review various additives used for their treatment. Finally, we examine the limitations and obstacles that exist in the development of the clinically relevant applications of these appealing technologies. This review defines different types of hydrogels and carefully elaborate the mechanisms by which they repair diabetic ulcers (DUs), summarizes the pathological process of DUs, and reviews various bioactivators used for their treatment.

Drug-loaded microbubble delivery system to enhance PD-L1 blockade immunotherapy with remodeling immune microenvironment.

BACKGROUND: Although programmed cell death protein 1 (PD-1)/ programmed cell death-ligand protein 1 (PD-L1) checkpoint blockade immunotherapy demonstrates great promise in cancer treatment, poor infiltration of T cells resulted from tumor immunosuppressive microenvironment (TIME) and insufficient accumulation of anti-PD-L1 (αPD-L1) in tumor sites diminish the immune response. Herein, we reported a drug-loaded microbubble delivery system to overcome these obstacles and enhance PD-L1 blockade immunotherapy. METHODS: Docetaxel (DTX) and imiquimod (R837)-loaded microbubbles (RD@MBs) were synthesized via a typical rotary evaporation method combined with mechanical oscillation. The targeted release of drugs was achieved by using the directional "bursting" capability of ultrasound-targeted microbubble destruction (UTMD) technology. The antitumor immune response by RD@MBs combining αPD-L1 were evaluated on 4T1 and CT26 tumor models. RESULTS: The dying tumor cells induced by DTX release tumor-associated antigens (TAAs), together with R837, promoted the activation, proliferation and recruitment of T cells. Besides, UTMD technology and DTX enhanced the accumulation of αPD-L1 in tumor sites. Moreover, RD@MBs remolded TIME, including the polarization of M2-phenotype tumor-associated macrophages (TAMs) to M1-phenotype, and reduction of myeloid-derived suppressor cells (MDSCs). The RD@MBs + αPD-L1 synergistic therapy not only effectively inhibited the growth of primary tumors, but also significantly inhibited the mimic distant tumors as well as lung metastases. CONCLUSION: PD-L1 blockade immunotherapy was enhanced by RD@MBs delivery system.

Institutional pressures as drivers of corporate green innovation: do provincial officials and CEOs matter?

Findings from prior studies regarding the relationship between national institutional pressures and corporate green innovation have been mixed. To address this gap, we consider the moderating effects of public agents (provincial officials) and private agents (corporate CEOs) to investigate corporate green innovation in response to institutional pressures. Using the method of difference-in-difference, we examine the data from 722 publicly listed Chinese firms between 2007 and 2019, a period associated with the implementation of China's Twelfth Five-Year Plan which increase the emphasis on social indicators for national development. Our results firstly show that institutional pressures caused by Twelfth Five-Year Plan significantly facilitate polluting-firms' green innovation relative to clean-firms, and the effect is stronger when public agents are more concerned about promotion to the central government or private agents have greater concerns for legitimacy, meanwhile not producing an a real "incentive effect" on corporate green innovation, but a "crowding-out effect" on existing innovation. Furthermore, results also suggest institutional pressures mainly induced polluting-firms' strategic innovation behaviors, and the incentive effects of institutional pressures on polluting-firms' green innovation are different in terms of firms' ownership and size. Our results generate important theoretical and practical implications.

Severe Burn Injury Significantly Alters the Gene Expression and m6A Methylation Tagging of mRNAs and lncRNAs in Human Skin.

N6-methyladenosine (m6A) modulates RNA metabolism and functions in cell differentiation, tissue development, and immune response. After acute burns, skin wounds are highly susceptible to infection and poor healing. However, our understanding of the effect of burn injuries on m6A methylation and their potential mechanism is still limited. Human m6A-mRNA&lncRNA Epitranscriptomic microarray was used to obtain comprehensive mRNA and lncRNA transcriptome m6A profiling and gene expression patterns after burn injuries in human skin tissue. Bioinformatic and functional analyses were conducted to find molecular functions. Microarray profiling showed that 65 mRNAs and 39 lncRNAs were significantly hypermethylated; 5492 mRNAs and 754 lncRNAs were significantly hypomethylated. Notably, 3989 hypomethylated mRNAs were down-expressed and inhibited many wound healing biological processes and pathways including in the protein catabolic process and supramolecular fiber organization pathway; 39 hypermethylated mRNAs were up-expressed and influenced the cell surface receptor signaling pathway and inflammatory response. Moreover, we validated that m6A regulators (METTL14, METTL16, ALKBH5, FMR1, and HNRNPC) were significantly downregulated after burn injury which may be responsible for the alteration of m6A modification and gene expression. In summary, we found that homeostasis in the skin was disrupted and m6A modification may be a potential mechanism affecting trauma infection and wound healing.

p53 downregulates PD-L1 expression via miR-34a to inhibit the growth of triple-negative breast cancer cells: a potential clinical immunotherapeutic target.

BACKGROUND: Compared with other breast cancer subtypes, triple-negative breast cancer (TNBC) has poorer responses to therapy and lower overall survival rates. The use of an inhibitor of immune checkpoint programmed cell death ligand 1 (PD-L1) is a promising treatment strategy and is approved for malignant tumors, especially for TNBC. p53 regulates various biological processes, but the association between p53 and immune evasion remains unknown. miR-34a is a known tumor suppressor and p53-regulated miRNA that is downregulated in several cancers; however, it has not been reported in TNBC. Herein, we aimed to explore the regulatory signaling axis among p53, miR-34a and PD-L1 in TNBC cells in vivo and in tissue and to improve our understanding of immunotherapy for TNBC. METHODS AND RESULTS: p53-EGFP, p53-siRNA and miR-34a mimics were transfected into TNBC cell lines, and the interaction between miR-34a and PD-L1 was analyzed via dual-luciferase reporter assays. We found that p53 could inhibit the expression of PD-L1 via miR-34a and that miR-34a could inhibit both cell activity and migration and promoted apoptosis and cytotoxicity in TNBC. Furthermore, miR-34a agomir was injected into MDA-MB-231 tumors of nude mice. The results showed that miR-34a could inhibit tumor growth and downregulate the expression of PD-L1 in vivo. A total of 133 TNBC tissue samples were analyzed by immunochemistry; the proportion of positive expression of PD-L1 was 57.14% (76/133), and the proportion of samples with negative expression of PD-L1 was 42.86% (57/133). CONCLUSION: Our research may provide a novel potential target for TNBC.

Two-dimensional wide-bandgap GeSe2 vertical ultraviolet photodetectors with high responsivity and ultrafast response speed.

Germanium selenide (GeSe2), as a typical member of 2D wide bandgap semiconductors (WBSs), shows great potential in ultraviolet (UV) optoelectronics due to its excellent flexibility, superior environmental stability, competitive UV absorption coefficient, and significant spectral selectivity. However, the GeSe2-based UV photodetector suffers from high operation voltages and low photocurrent, which prevents its practical imaging applications. In this work, we report an elevated photocurrent generation in a vertical stacking graphene/GeSe2/graphene heterostructure with low operation voltage and low power consumption. Efficient collection of photoexcited carriers in GeSe2 through graphene electrodes results in outstanding UV detection properties, including a pronounced responsivity of 37.1 A W-1, a specific detectivity of 8.83 × 1011 Jones, and an ultrahigh on/off ratio (∼105) at 355 nm. In addition, building a Schottky barrier between GeSe2 and graphene and reducing the channel length can increase the photoresponse speed to ∼300 µs. These accomplishments set the stage for future optoelectronic applications of vertical 2D WBS heterostructure UV photodetectors.

Injectable versatile liquid-solid transformation implants alliance checkpoint blockade for magnetothermal dynamic-immunotherapy.

The ongoing circulating energy loss, low reactive oxygen species (ROS) accumulation and poor immunogenicity of tumors make it difficult to induce sufficient immunogenic cell death (ICD) in the tumor immunosuppressive microenvironment (TIME), resulting in unsatisfactory immunotherapy efficacy. Furthermore, for highly malignant tumors, simply enhancing ICD is insufficient for exhaustively eliminating the tumor and inhibiting metastasis. Herein, we propose a unique magnetothermal-dynamic immunotherapy strategy based on liquid-solid transformation porous versatile implants (Fe3O4/AIPH@PLGA) that takes advantage of less energy loss and avoids ongoing circulating losses by minimally invasive injection into tumors. In addition, the magnetothermal effect regresses and eliminates tumors that are not limited by penetration to simultaneously trigger 2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) decomposition and generate a large amount of oxygen-irrelevant free radicals and heat shock protein (HSP) accumulation by heating, evoking both intracellular oxidative stress and endoplasmic reticulum (ER) stress to induce large-scale ICD and enhance tumor immunogenicity. More importantly, in orthotopic bilateral breast tumor models, a significant therapeutic effect was obtained after combining amplified ICD with CTLA4 checkpoint blockade. The 21-day primary and distant tumor inhibition rates reached 90%, and the underlying mechanism of the effective synergetic strategy of inducing the T-cell-related response, the immune memory effect and TIME reprogramming in vivo was verified by immune cell analyses. This remarkable therapeutic effect provides a new direction for antitumor immunotherapy based on magnetothermally controlled oxygen-independent free radical release.

Comparative genomic analysis of the COBRA genes in six Rosaceae species and expression analysis in Chinese white pear (Pyrus bretschneideri).

COBRA-Like (COBL) genes encode a glycosylphosphatidylinositol (GPI) anchoring protein unique to plants. In current study, 87 COBRA genes were identified in 6 Rosaceae species, including Pyrus bretschneideri (16 genes), Malus domestica (22 genes), Fragaria vesca (13 genes), Prunus mume (11 genes), Rubus occidentalis (13 genes) and Prunus avium (12 genes). We revealed the evolution of the COBRA gene in six Rosaceae species by phylogeny, gene structure, conservative sequence, hydrophobicity analysis, gene replication events and sliding window analysis. In addition, based on the analysis of expression patterns in pear fruit combined with bioinformatics, we identified PbCOBL12 and PbCOBL13 as potential genes regulating secondary cell wall (SCW) formation during pear stone cell development. This study aimed to understand the evolutionary relationship of the COBRA gene in Rosaceae species, clarify the potential function of COBRA in pear fruit development, and provide essential theoretical basis and gene resources for improving pear fruit quality through genetical modification mechanism.