Coupling coordination between electricity and economy: China as an example.

The benign coupling coordination between electricity (EL) and economy (EC) contributes to a better environment and sustainability. This study explores whether EL and EC can coordinate theoretically, how to evaluate their coordination, what the statuses are, and how to enhance coupling coordination levels (CCL). Specifically, we select the data from 2011 to 2020 of the 31 provincial regions of China, use information entropy weight and the technique for order preference by similarity to an ideal solution method, establish the theoretical coupling coordination mechanism and the evaluation index system to measure CCL temporally-spatially and propose policy implications based on prediction tendencies. We find that most regions' CCLs fluctuate temporally with mild upward trends, indicating the much more benign coupling coordination status; the spatial distributions are uneven with narrowing gaps. However, future CCL gaps may increase; therefore, differentiated policy implications are needed, such as encouraging balanced-coordination policies, innovating for higher-quality coordination, and cooperating for intelligence and wealth transfer. This study is conducive to theoretically describing the coupling coordination mechanism between EL and EC, providing new insights for CCL evaluation and the coordination practice for different regions.

Machine learning-based prediction of the risk of moderate-to-severe catheter-related bladder discomfort in general anaesthesia patients: a prospective cohort study.

BACKGROUND: Catheter-related bladder discomfort (CRBD) commonly occurs in patients who have indwelling urinary catheters while under general anesthesia. And moderate-to-severe CRBD can lead to significant adverse events and negatively impact patient health outcomes. However, current screening studies for patients experiencing moderate-to-severe CRBD after waking from general anesthesia are insufficient. Constructing predictive models with higher accuracy using multiple machine learning techniques for early identification of patients at risk of experiencing moderate-to-severe CRBD during general anesthesia resuscitation. METHODS: Eight hundred forty-six patients with indwelling urinary catheters who were resuscitated in a post-anesthesia care unit (PACU). Trained researchers used the CRBD 4-level assessment method to evaluate the severity of a patient's CRBD. They then inputted 24 predictors into six different machine learning algorithms. The performance of the models was evaluated using metrics like the area under the curve (AUC). RESULTS: The AUCs of the six models ranged from 0.82 to 0.89. Among them, the RF model displayed the highest predictive ability, with an AUC of 0.89 (95%CI: 0.87, 0.91). Additionally, it achieved an accuracy of 0.93 (95%CI: 0.91, 0.95), 0.80 sensitivity, 0.98 specificity, 0.94 positive predictive value (PPV), 0.92 negative predictive value (NPV), 0.87 F1 score, and 0.07 Brier score. The logistic regression (LR) model has achieved good results (AUC:0.87) and converted into a nomogram. CONCLUSIONS: The study has successfully developed a machine learning prediction model that exhibits excellent predictive capabilities in identifying patients who may develop moderate-to-severe CRBD after undergoing general anesthesia. Furthermore, the study also presents a nomogram, which serves as a valuable tool for clinical healthcare professionals, enabling them to intervene at an early stage for better patient outcomes.

The developmental dyslexia scale for standard mandarin: A study among early primary students.

BACKGROUND: Developmental dyslexia (DD) is a prevalent neurodevelopmental disease that poses challenges in both early intervention and long-term development for children with DD. However, there is a lack of a standardized and comprehensive tool for the diagnosis of DD in Mainland China. AIM: To develop a standardized tool (i.e., Developmental Dyslexia Scale for Standard Mandarin [DDSSM]) for the diagnosis of DD in Mainland China and evaluate its reliability and validity. METHODS AND PROCEDURES: DDSSM consists of 10 subtests. The initial draft was created after Delphi expert consultation, and the final version was revised to improve discriminability with a pilot study involving 450 children from grades 1-3. The reliability and validity were then confirmed with 53 children from grades 1-2. OUTCOMES AND RESULTS: The Delphi expert consultation demonstrated that the expert panel had good authority, and that all agreed on the subtest setup. The DDSSM exhibited great internal consistency. Confirmatory factor analysis revealed that the model aligns with the theoretical structure (P > 0.05, χ2/df < 2.00, root-mean-square error of approximation (RMSEA) < 0.08, comparative fit index (CFI) > 0.90, TLI > 0.90). The Dyslexia Checklist for Chinese Children and children's academic performance agreed well with the DDSSM. CONCLUSIONS AND IMPLICATIONS: The DDSAM is reliable and valid for assessing and diagnosing DD in Standard Mandarin-speaking primary school children from grades 1-2. WHAT THIS PAPER ADDS?: Although a number of scales and tools have been proposed for assessing developmental dyslexia (DD) in Chinese, there is still a lack of diagnostic tools for Mandarin Chinese in Mainland China. In this study, we developed one of the most comprehensive diagnostic tools for DD in Mandarin Chinese for lower graders. We included visual-spatial attention (VA) and compounding awareness (CA), two tests that have been recently suggested as reliable measures for identifying DD in the Chinese language. This assessment tool has been verified for robust reliability and validity. This study also provided confirmation of the core deficits of DD in Chinese, which were orthographic awareness (OA). In addition, VA, rapid automatized naming (RAN) and morphological awareness (MA) were found to be the most important cognitive abilities for word reading in Chinese lower graders in this study.

Oxytocin with calcium vs. oxytocin for induction of labor in women with term premature rupture of membranes: A randomized controlled trial: Oxytocin with calcium gluconate for labor induction.

BACKGROUND: Intravenous calcium administration has shown promise in enhancing uterine contractions and reducing blood loss during cesarean section, but this regimen has not been compared in vaginal labor induction. OBJECTIVE: To determine the efficacy of oxytocin combined with calcium versus oxytocin alone for inducing labor among women with term premature rupture of membranes (PROM). STUDY DESIGN: This single-blind, randomized control trial was conducted between October 2022 and May 2023 in a tertiary university hospital. Patients diagnosed with PROM were randomly allocated into two groups. The intervention group received a bolus of 10 mL of calcium gluconate followed by a continuous infusion of oxytocin via a pump (n = 210), whereas the control group received only oxytocin infusion (n = 218). The primary outcome was successful vaginal deliveries within 24 hours of labor induction. Secondary outcomes included the interval from labor induction to delivery, vaginal delivery blood loss, and maternal and neonatal complications. RESULTS: Baseline characteristics, including maternal age, BMI, Bishop score before labor induction, were comparable between groups. The rate of vaginal delivery within 24 hours of labor induction was statistically higher in the intervention group (79.52% vs. 70.64%; P = 0.04). Participants in intervention group experienced a shortened interval between induction and delivery (10.48 h vs. 11.25h; P = 0.037), and demonstrated a higher success rate in induction of labor assessed by the onset of active phase (93.80% vs. 87.61%; P = 0.04) without increasing the cesarean rate. Reduced hemorrhage was presented in the intervention group (242.5ml vs. 255.0ml; P = 0.0015) while the maternal and neonatal outcomes were comparable between groups. CONCLUSION: The co-administration of calcium and oxytocin in labor induction among pregnancies with PROM was more efficient and safer than oxytocin alone. Our research suggests that the combination therapy of calcium and oxytocin may offer significant advantages during the process of labor induction and result in better outcomes.

Thirdhand smoke exposure promotes gastric tumor development in mouse and human.

The pollution of indoor environments and the consequent health risks associated with thirdhand smoke (THS) are increasingly recognized in recent years. However, the carcinogenic potential of THS and its underlying mechanisms have yet to be thoroughly explored. In this study, we examined the effects of short-term THS exposure on the development of gastric cancer (GC) in vitro and in vivo. In a mouse model of spontaneous GC, CC036, we observed a significant increase in gastric tumor incidence and a decrease in tumor-free survival upon THS exposure as compared to control. RNA sequencing of primary gastric epithelial cells derived from CC036 mice showed that THS exposure increased expression of genes related to the extracellular matrix and cytoskeletal protein structure. We then identified a THS exposure-induced 91-gene expression signature in CC036 and a homologous 84-gene signature in human GC patients that predicted the prognosis, with secreted phosphoprotein 1 (SPP1) and tribbles pseudokinase 3 (TRIB3) emerging as potential targets through which THS may promote gastric carcinogenesis. We also treated human GC cell lines in vitro with media containing various concentrations of THS, which, in some exposure dose range, significantly increased their proliferation, invasion, and migration. We showed that THS exposure could activate the epithelial-mesenchymal transition (EMT) pathway at the transcript and protein level. We conclude that short-term exposure to THS is associated with an increased risk of GC and that activation of the EMT program could be one potential mechanism. Increased understanding of the cancer risk associated with THS exposure will help identify new preventive and therapeutic strategies for tobacco-related disease as well as provide scientific evidence and rationale for policy decisions related to THS pollution control to protect vulnerable subpopulations such as children.

De novo Whole-Genome Assembly of the 10-Gigabase Fokienia Hodginsii Genome to Reveal Differential Epigenetic Events Between Callus and Xylem.

Fokienia hodginsii (F. hodginsii), belonging to the genus Fokienia of the Cupressaceae. F. hodginsii has significant application value due to its wood properties and great research value in evolutionary studies as a gymnosperm. However, the genome of F. hodginsii remains unknown due to the large size of gymnosperms genome. Pacific Bioscience sequencing, Hi-C mapping, whole-genome Bisulfite Sequencing (BS-Seq), long-read isoform sequencing (Iso-Seq), direct RNA sequencing (DRS), quantitative proteomics, and metabonomics analysis are employed to facilitate genome assembly, gene annotation, and investigation into epigenetic mechanisms. In this study, the 10G F. hodginsii genome is assembled into 11 chromosomes. Furthermore, 50 521 protein-coding genes are annotated and determined that 65% of F. hodginsii genome comprises repetitive sequences. It is discovered that transposable element (TE)-including introns is associated with higher expression. The DNA methylome of F. hodginsii reveals that xylem has a higher DNA methylation level compared to callus. Moreover, DRS reveals the significant alterations in RNA full-length ratio, which potentially associated with poly(A) length (PAL) and alternative polyadenylation (APA). Finally, the morphology measurement and metabonomics analysis revealed the difference of 14 cultivars. In summary, the genomes and epigenetics datasets provide a molecular basis for callus formation in the gymnosperm family.

Characterization of a secondary palmitoleoyltransferase of lipid A in Vibrio parahaemolyticus.

The detection of pathogenicity and immunogenicity in Vibrio parahaemolyticus poses a significant challenge due to its threat to human health and food safety, which is strongly correlated with lipid A. Lipid A, a critical component found in most Gram-negative bacteria, functions as a hydrophobic anchor for lipopolysaccharide. V. parahaemolyticus synthesizes multiple lipid A species with various secondary acyl chains. In this study, a secondary acyltransferase of lipid A encoded by VP_RS08405 in V. parahaemolyticus was identified. Based on sequence alignment analysis, V. parahaemolyticus VP_RS08405 has high homology to E. coli lpxL, lpxM and lpxP which encode the three secondary acyltransferases of lipid A. Therefore, V. parahaemolyticus VP_RS08405 was cloned into pBAD33, and the resulting pB08405 was introduced in E. coli mutants WHL00 in which lpxL was deleted, WHM00 in which lpxM was deleted, WHP00 in which lpxP was deleted, and WH300 in which lpxL, lpxM and lpxP were deleted. The recombinant strains WHL00/pB08405, WHM00/pB08405, WHP00/pB08405, WH300/pB08405, as well as their vector controls, were grown at normal and low temperatures. Lipid A species were isolated from the above strains and analyzed by using high-performance liquid chromatography-tandem mass spectrometry and thin-layer chromatography. After comparing the secondary acyl alterations of lipid A from different recombinant strains, it is concluded that VP_RS08405 specifically catalyzed the addition of a palmitoleate to the 2'-position of lipid A and its activity is not temperature-sensitive. In addition, to determine the dependence of VP_RS08405 on Kdo, VP_RS08405 was overexpressed in E. coli mutants WH001 in which waaA was deleted, and WH400 in which waaA, lpxL, lpxM and lpxP were deleted. Lipid A species were isolated from WH001/pB08405 and WH400/pB08405, and analyzed. The results show that the function of VP_RS08405 is Kdo-dependent. These findings provide a better understanding of the structural diversity of lipid A in V. parahaemolyticus.

Expression of Iron Metabolism Genes Is Potentially Regulated by DOF Transcription Factors in Dendrocalamus latiflorus Leaves.

Transcription factors (TFs) are crucial pre-transcriptional regulatory mechanisms that can modulate the expression of downstream genes by binding to their promoter regions. DOF (DNA binding with One Finger) proteins are a unique class of TFs with extensive roles in plant growth and development. Our previous research indicated that iron content varies among bamboo leaves of different colors. However, to our knowledge, genes related to iron metabolism pathways in bamboo species have not yet been studied. Therefore, in the current study, we identified iron metabolism related (IMR) genes in bamboo and determined the TFs that significantly influence them. Among these, DOFs were found to have widespread effects and potentially significant impacts on their expression. We identified specific DOF members in Dendrocalamus latiflorus with binding abilities through homology with Arabidopsis DOF proteins, and established connections between some of these members and IMR genes using RNA-seq data. Additionally, molecular docking confirmed the binding interactions between these DlDOFs and the DOF binding sites in the promoter regions of IMR genes. The co-expression relationship between the two gene sets was further validated using q-PCR experiments. This study paves the way for research into iron metabolism pathways in bamboo and lays the foundation for understanding the role of DOF TFs in D. latiflorus.

Organocatalyzed Asymmetric Michael Addition of 3-Fluorooxindole to Vinylidene Bisphosphonates.

Both the 3-fluorooxindole and germinal bisphosphonate structural motifs are prevalent in bioactive molecules because of their associated biological activities. We describe an approach to accessing 3,3-disubstituted 3-fluorooxindoles bearing a geminal bisphosphate fragment through a highly enantioselective Michael addition reaction between 3-fluorooxindoles and vinylidene bisphosphonates. These reactions are catalyzed by a commercially available cinchona alkaloid catalyst, have a broad substrate scope concerning 3-fluorooxindoles, and provide the corresponding addition products in a yield of up to 95% with an enantiomeric excess of up to 95%. A reasonable reaction pathway to explain the observed stereochemistry is also proposed.

Comprehensive characterization of B7 family members in breast cancer: B7-H5 switch reverses breast cancer from "immuno-cold" into "immuno-hot" status.

The members of the classic B7 family regulate the immune microenvironment of several malignant tumors. However, the potential relationship between the B7 family and the breast cancer (BrCa) tumor immune microenvironment has remained elusive. In the present study, we provide a comprehensive explanation of the expression, clinical significance, mutation, and immune cell infiltration of B7 family molecules in BrCa. First, we recruited 10 patients with BrCa surgery from the Wuxi Maternal and Child Health Hospital and performed single-cell RNA sequencing (scRNA-seq) analysis to investigate the distribution of B7 family members in multiple immune cell subsets. We focused on B7-2, B7-H3, and B7-H5 molecules of the B7 family and constructed tumor microarrays by self-recruiting patients to perform multiple immunohistochemical (mIHC) analyses and study tumor expression of B7-2, B7-H3, B7-H5 and CD8+ immune cell infiltration. B7-H5 displayed a strong correlation with CD8+ immune cell infiltration. In summary, B7-H5 provides a new perspective for the identification of immunothermal subtypes of BrCa and could function as a switch to reverse BrCa from an "immunologically cold" state to an "immunologically hot" state.

The crosstalk between cell death and pregnancy related diseases: A narrative review.

Programmed cell death is intricately linked to various physiological phenomena such as growth, development, and metabolism, as well as the proper function of the pancreatic ß cell and the migration and invasion of trophoblast cells in the placenta during pregnancy. Traditional and recently identified programmed cell death include apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis. In addition to cancer and degenerative diseases, abnormal activation of cell death has also been implicated in pregnancy related diseases like preeclampsia, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, fetal growth restriction, and recurrent miscarriage. Excessive or insufficient cell death and pregnancy related diseases may be mutually determined, ultimately resulting in adverse pregnancy outcomes. In this review, we systematically describe the characteristics and mechanisms underlying several types of cell death and their roles in pregnancy related diseases. Moreover, we discuss potential therapeutic strategies that target cell death signaling pathways for pregnancy related diseases, hoping that more meaningful treatments will be applied in clinical practice in the future.

Application, knowledge and training needs regarding comprehensive geriatric assessment among geriatric practitioners in healthcare institutions: a cross-sectional study.

BACKGROUND: This study aimed to investigate the actual application, knowledge, and training needs of comprehensive geriatric assessment (CGA) among geriatric practitioners in China. METHODS: A total of 225 geriatric practitioners attending the geriatric medicine or geriatric nursing training were recruited for this cross-sectional study. The questionnaire included demographics, healthcare institution characteristics, the actual application, knowledge, training needs, and barriers to CGA and geriatric syndromes (GS). RESULTS: Physicians and nurses were 57.3% and 42.7%, respectively. 71.1% were female, with a median age was 35 years. Almost two-thirds (140/225) of geriatric practitioners reported exposure to CGA in their clinical practice. The top five CGA evaluation items currently used were malnutrition risk (49.8%), fall risk (49.8%), activity of daily living (48.0%), pain (44.4%), and cognitive function (42.7%). Median knowledge scores for the management procedures of GS ranged from 2 to 6. Physicians identified medical insurance payment issues (29.5%) and a lack of systematic specialist knowledge and technology (21.7%) as the two biggest barriers to practicing geriatrics. Nurses cited a lack of systematic specialist knowledge and technology (52.1%) as the primary barrier. In addition, physicians and nurses exhibited significant differences in their knowledge of CGA-specific evaluation items and management procedures for GS (all P < 0.05). However, there were no significant differences in their training needs, except for polypharmacy. CONCLUSIONS: The rate of CGA application at the individual level, as well as the overall knowledge among geriatric practitioners, was not adequate. Geriatric education and continuous training should be tailored to address the specific roles of physicians and nurses, as well as the practical knowledge reserves, barriers, and training needs they face.

Characterization of a secondary hydroxy-acyltransferase for lipid A in Vibrio parahaemolyticus.

Lipid A plays a crucial role in Vibrio parahaemolyticus. Previously we have reported the diversity of secondary acylation of lipid A in V. parahaemolyticus and four V. parahaemolyticus genes VP_RS08405, VP_RS01045, VP_RS12170, and VP_RS00880 exhibiting homology to the secondary acyltransferases in Escherichia coli. In this study, the gene VP_RS12170 was identified as a specific lipid A secondary hydroxy-acyltransferase responsible for transferring a 3-hydroxymyristate to the 2'-position of lipid A. Four E. coli mutant strains WHL00, WHM00, WH300, and WH001 were constructed, and they would synthesize lipid A with different structures due to the absence of genes encoding lipid A secondary acyltransferases or Kdo transferase. Then V. parahaemolyticus VP_RS12170 was overexpressed in W3110, WHL00, WHM00, WH300, and WH001, and lipid A was isolated from these strains and analyzed by using thin-layer chromatography and high-performance liquid chromatography-tandem mass spectrometry. The detailed structural changes of lipid A in these mutant strains with and without VP_RS12170 overexpression were compared and conclude that VP_RS12170 can specifically transfer a 3-hydroxymyristate to the 2'-position of lipid A. This study also demonstrated that the function of VP_RS12170 is Kdo-dependent and its favorite substrate is Kdo-lipid IVA. These findings give us better understanding the biosynthetic pathway and the structural diversity of V. parahaemolyticus lipid A.

Human Breast Milk Exosomal miRNAs are Influenced by Premature Delivery and Affect Neurodevelopment.

SCOPE: This study investigates the exosomal microRNA (miRNA) profiles of term and preterm breast milk, including the most abundant and differentially expressed (DE) miRNAs, and their impact on neurodevelopment in infants. METHODS AND RESULTS: Mature milk is collected from the mothers of term and preterm infants. Using high-throughput sequencing and subsequent data analysis, exosomal miRNA profiles of term and preterm human breast milk (HBM) are acquired and it is found that the let-7 and miR-148 families are the most abundant miRNAs. Additionally, 23 upregulated and 15 downregulated miRNAs are identified. MiR-3168 is the most upregulated miRNA in preterm HBM exosome, exhibiting targeting activity toward multiple genes involved in the SMAD and MAPK signaling pathways and playing a crucial role in early neurodevelopment. Additionally, the effects of miR-3168 on neurodevelopment is confirmed and it is determined that it is an essential factor in the differentiation of neural stem cells (NSCs). CONCLUSION: This study demonstrates that miRNA expression in breast milk exosomes can be influenced by preterm delivery, thereby potentially impacting neurodevelopment in preterm infants.

Integrated 16S rRNA sequencing and metagenomics insights into microbial dysbiosis and distinct virulence factors in inflammatory bowel disease.

Introduction: The escalation of urbanization correlates with rising rates of inflammatory bowel disease (IBD), necessitating research into new etiological factors. This study aims to elucidate the gut microbiota profiles in IBD patients and compare them with healthy controls in a western city of China. Methods: We conducted a multicenter case-control study from the end of 2020, using 16S rRNA gene sequencing (n = 36) and metagenomic sequencing (n = 12) to analyze the gut microbiota of newly diagnosed IBD patients, including those with Crohn's disease (CD) and ulcerative colitis (UC). Results: Our results demonstrated a significant enrichment of the phylum Proteobacteria, particularly the genus Escherichia-Shigella, in CD patients. Conversely, the genus Enterococcus was markedly increased in UC patients. The core gut microbiota, such as the Christensenellaceae R-7 group, Fusicatenibacter, and Holdemanella, were primarily identified in healthy subjects. Additionally, significant interactions between the microbiome and virulence factors were observed. Discussion: The findings suggest that oxidative stress may play a pivotal role in the pathology of IBD. This study contributes to the growing dialogue about the impact of gut microbiota on the development of IBD and its variations across different geographies, highlighting potential avenues for further research.

Timing of early water intake post-general anaesthesia: a systematic review and meta-analysis.

BACKGROUND: Early water intake has gained widespread attention considering enhanced recovery after surgery (ERAS). In the present systematic evaluation and meta-analysis, we assessed the effects of early water intake on the incidence of vomiting and aspiration in adult patients who received general anaesthesia on regaining consciousness during the resuscitation period. OBJECTIVE: To systematically analyse the results of randomised controlled trials on early postoperative water intake in patients who underwent different types of surgery under general anaesthesia, both at home and abroad, to further explore the safety and application of early water intake and provide an evidence-based foundation for clinical application. DESIGN: Systematic review and meta-analysis. METHODS: To perform the systematic evaluation and meta-analysis, we searched the Web of Science, CINAHL, Embase, PubMed, Cochrane Library, Sinomed, China National Knowledge Infrastructure (CNKI), Wanfang, and Vipshop databases to identify randomised controlled trial studies on early water intake in adult patients who received general anaesthesia. RESULTS: Herein, we included 10 publications with a total sample size of 5131 patients. Based on statistical analysis, there was no statistically significant difference in the incidence of vomiting (odds ratio [OR] = 0.81; 95% confidence interval [CI] [0.58-1.12]; p = 0.20; I-squared [I2] = 0%) and aspiration (OR = 0.78; 95%CI [0.45-1.37]; p = 0.40; I2 = 0%) between the two groups of patients on regaining consciousness post-general anaesthesia. CONCLUSION: Based on the available evidence, early water intake after regaining consciousness post-anaesthesia did not increase the incidence of adverse complications when compared with traditional postoperative water abstinence. Early water intake could effectively improve patient thirst and facilitate the recovery of gastrointestinal function.

Variability in Leaf Color Induced by Chlorophyll Deficiency: Transcriptional Changes in Bamboo Leaves.

The diversity of leaf characteristics, particularly leaf color, underscores a pivotal area of inquiry within plant science. The synthesis and functionality of chlorophyll, crucial for photosynthesis, largely dictate leaf coloration, with varying concentrations imparting different shades of green. Complex gene interactions regulate the synthesis and degradation of chlorophyll, and disruptions in these pathways can result in abnormal chlorophyll production, thereby affecting leaf pigmentation. This study focuses on Bambusa multiplex f. silverstripe, a natural variant distinguished by a spectrum of leaf colors, such as green, white, and green-white, attributed to genetic variations influencing gene expression. By examining the physiological and molecular mechanisms underlying chlorophyll anomalies and genetic factors in Silverstripe, this research sheds light on the intricate gene interactions and regulatory networks that contribute to leaf color diversity. The investigation includes the measurement of photosynthetic pigments and nutrient concentrations across different leaf color types, alongside transcriptomic analyses for identifying differentially expressed genes. The role of key genes in pathways such as ALA biosynthesis, chlorophyll synthesis, photosynthesis, and sugar metabolism is explored, offering critical insights for advancing research and plant breeding practices.

A promising target for breast cancer: B7-H3.

Breast cancer (BC) is the second-leading factor of mortality for women globally and is brought on by a variety of genetic and environmental causes. The conventional treatments for this disease have limitations, making it difficult to improve the lifespan of breast cancer patients. As a result, extensive research has been conducted over the past decade to find innovative solutions to these challenges. Targeting of the antitumor immune response through the immunomodulatory checkpoint protein B7 family has revolutionized cancer treatment and led to intermittent patient responses. B7-H3 has recently received attention because of its significant demodulation and its immunomodulatory effects in many cancers. Uncontrolled B7-H3 expression and a bad outlook are strongly associated, according to a substantial body of cancer research. Numerous studies have shown that BC has significant B7-H3 expression, and B7-H3 induces an immune evasion phenotype, consequently enhancing the survival, proliferation, metastasis, and drug resistance of BC cells. Thus, an innovative target for immunotherapy against BC may be the B7-H3 checkpoint.In this review, we discuss the structure and regulation of B7-H3 and its double costimulatory/coinhibitory function within the framework of cancer and normal physiology. Then we expound the malignant behavior of B7-H3 in BC and its role in the tumor microenvironment (TME) and finally focus on targeted drugs against B7-H3 that have opened new therapeutic opportunities in BC.

Associations between HIFs and tumor immune checkpoints: mechanism and therapy.

Hypoxia, which activates a variety of signaling pathways to enhance tumor cell growth and metabolism, is among the primary features of tumor cells. Hypoxia-inducible factors (HIFs) have a substantial impact on a variety of facets of tumor biology, such as epithelial-mesenchymal transition, metabolic reprogramming, angiogenesis, and improved radiation resistance. HIFs induce hypoxia-adaptive responses in tumor cells. Many academics have presented preclinical and clinical research targeting HIFs in tumor therapy, highlighting the potential applicability of targeted HIFs. In recent years, the discovery of numerous pharmacological drugs targeting the regulatory mechanisms of HIFs has garnered substantial attention. Additionally, HIF inhibitors have attained positive results when used in conjunction with traditional oncology radiation and/or chemotherapy, as well as with the very promising addition of tumor immunotherapy. Immune checkpoint inhibitors (CPIs), which are employed in a range of cancer treatments over the past decades, are essential in tumor immunotherapy. Nevertheless, the use of immunotherapy has been severely hampered by tumor resistance and treatment-related toxicity. According to research, HIF inhibitors paired with CPIs may be game changers for multiple malignancies, decreasing malignant cell plasticity and cancer therapy resistance, among other things, and opening up substantial new pathways for immunotherapy drug development. The structure, activation mechanisms, and pharmacological sites of action of the HIF family are briefly reviewed in this work. This review further explores the interactions between HIF inhibitors and other tumor immunotherapy components and covers the potential clinical use of HIF inhibitors in combination with CPIs.

High B7-H3 expression with low PD-L1 expression identifies armored-cold tumors in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is generally regarded as the most aggressive subtype among breast cancers, but exhibits higher chemotherapeutic and immunotherapeutic responses due to its unique immunogenicity. Thus, appropriate discrimination of subtypes is critical for guiding therapeutic options in clinical practice. In this research, using multiple in-house and public cohorts, we investigated the expression features and immuno-correlations of B7-H3 in breast cancer and checked the anti-tumor effect of the B7-H3 monoclonal antibody in a mouse model. We also developed a novel classifier combining B7-H3 and PD-L1 expression in TNBC. B7-H3 was revealed to be related to immuno-cold features and accumulated collagen in TNBC. In addition, targeting B7-H3 using the monoclonal antibody significantly suppressed mouse TNBC growth, reversed the armored-cold phenotype, and also boosted anti-PD-1 immunotherapy. In addition, patients with B7-H3 high and PD-L1 low expression showed the lowest anti-tumor immune infiltration, the highest collagen level, and the lowest therapeutic responses to multiple therapies, which mostly belong to armored-cold tumors. Overall, this research provides a novel subtyping strategy based on the combination of B7-H3/PD-L1 expression, which leads to a novel approach for the management of TNBC.