Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.

Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.

Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.

Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.

Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Objective:To analyze the effect of birth parity on life expectancy (LE) and healthy life expectancy (HLE) among rural women.Method:A total of 15 304 women aged 40 to 79 years who participated in baseline and follow-up surveys were selected from a rural cohort in Henan province. The LE and HLE of women with different birth parity were calculated by using multi-state life table.Results:There were 1 195 (7.8%), 7 782 (50.8%), 3 867 (25.3%) and 2 460 (16.1%) women with 1, 2, 3 and 4 birth parities, respectively, and the M ( Q1 and Q3) of age were 50.3 (47.3, 53.4) and 53.3 (48.8, 60.7), 62.6 (55.4, 66.9) and 69.5 (64.7, 73.4) years old, respectively. LE at 40 years old was 44.5, 44.8, 45.1 and 45.4 years old, and HLE was 17.7, 18.3, 18.8 and 19.3 years old, respectively. LE at age 40 increased by 0.3, 0.6, and 0.9 years in women with 2, 3, and 4 birth parities or more and HLE increased by 0.5, 1.1, and 1.6 years, respectively, compared with women with 1 birth parity. For women with higher and lower socioeconomic status who had 4 birth parities or more, the LE at age 40 was 47.1 and 43.9 years, respectively, an increase of 0.2 and 0.1 years over women with 1 birth parity, respectively; and the HLE was 20.4 and 18.7 years, respectively, an increase of 1.4 and 1.3 years over women with 1 birth parity, respectively. Conclusion:LE and HLE show an upward trend with the increase of birth parity among rural women.

Objective:To develop a recombinant protein vaccine based on KPC-2, a drug resistance target in Klebsiella pneumoniae, and evaluate its immunogenicity, protective efficacy and mechanism in a mouse model of pneumonia. Methods:KPC-2 was expressed in Escherichia coli and purified using GST affinity chromatography. A recombinant protein vaccine was prepared with KPC-2 and used to immunize New Zealand rabbits through subcutaneous injection. Serum samples were isolated from cardiac blood and Protein G chromatography was used to purify polyclonal antibodies against KPC-2. Opsonophagocytic killing assay was used to assess the bactericidal activity of the polyclonal antibodies in vitro. Female BALB/c mice were immunized three times with the recombinant protein vaccine, and the titers of specific IgG antibodies in serum were measured by indirect ELISA. One week after the last vaccination, the mice were infected with Klebsiella pneumoniae strain SRT through tracheal intubation, and received a single intravenous dose of meropenem (0.1 mg) 1 h later. The protective efficacy of the KPC-2 recombinant protein vaccine was evaluated by comparing the survival rates, bacterial colonization and histopathological changes between vaccine group and adjuvant group as well as the survival rates between meropenem group and normal saline group. Moreover, the protective efficacy of polyclonal antibodies against KPC-2 was evaluated through passive immunization. Results:The level of specific IgG antibodies in serum was significantly higher in the vaccine group than in the adjuvant group ( t=4.325, P<0.05). The survival rate in the vaccine group was also higher than that of the adjuvant group [70% (7/10) vs 10% (1/10), P<0.05]. Furthermore, lung inflammation was less severe and bacterial burden was reduced in the vaccine group as compared with those of the control group ( t=3.127, P<0.05). Both active and passive vaccination strategies demonstrated strong protective efficacy against Klebsiella pneumoniae infection, and had a synergistic effect when used in combination with antibiotic therapy. The polyclonal antibodies against KPC-2 had bactericidal activity in vitro ( t=5.427, P<0.05). Conclusions:The prepared KPC-2 vaccine has better immunogenicity and protective efficacy. It can induce strong humoral immune responses. This study suggest that drug resistance target may be used as a candidate antigen for future vaccine development.

Bone metabolism refers to the decomposition and anabolism occurring during bone remodeling， and its balance is regulated by bone resorption and bone formation. A slight deviation of this balance causes various skeletal diseases， such as osteoporosis and renal osteodystrophy. Traditional Chinese medicine （TCM） monomers and compounds have certain advantages in treating bone metabolism diseases. The Wnt signaling pathway includes the canonical Wnt signaling pathway， dependent on β-catenin， and the non-canonical Wnt signaling pathway， independent of β-catenin. Both types of pathways can maintain bone metabolism balance by regulating bone formation and bone resorption and are essential for bone development， bone mass maintenance， and bone remodeling. A variety of TCM monomers （albiflorin， catalpol and icariin） and formulas （Zuogui pill， Yishen gugu prescription， Duzhong jiangu prescription， etc.） have been confirmed to promote differentiation of bone marrow mesenchymal stem cells， proliferation and differentiation of osteoblasts， bone injury repair， and osteoporosis improvement by activating the Wnt signaling pathway in recent years. Here， this article summarizes the research progress in the Wnt signaling pathway regulation of bone metabolism by TCM monomers and compounds to provide ideas for the clinical application of TCM and the research and development of new drugs for the prevention and treatment of bone metabolism diseases.

Objective The oxidative damage of DNA can be caused by excessive levels of Reactive oxygen species(ROS).Monitoring of DNA oxidative damage enables effective evaluation of ROS damage effects.Although the detection of DNA damage effects based on microbial sensor allows quantitative analysis of oxidative damage,the ROS clearance mechanism existed in bacterial will affect the sensitive of detection.The work of this article is to knockout the key genes of ROS clearance mechanism and construct an antioxidant gene-knock-out microbial sensor.The microbial sensor can realize sensitive monitoring of DNA damage effects and then evaluates the damage effects of cells by ROS.Methods The antioxidant damage genes of bacterial ahpCF,katE and katG were knocked out by λ-Red homologous recombination and antioxidant gene-knockout microbial sensor was constructed.The nalidixic acid sodium salt and UV irradiation were used to characterize the performance for monitoring of DNA damage effects.Results The antioxidant gene-knockout microbial sensors ΔahpC,ΔahpCF/ΔkatEG and ΔahpCF/ΔkatE/ΔkatG were constructed successfully.The results showed that the microbial sensor ΔahpCF/ΔkatE/ΔkatGl had the highest sensitive of damage effects and the limit of detection for nalidixic acid sodium salt was 0.40 μmol/L.In addition,1.80 min of UV irradiation(254 nm)was sufficient to induce a significant fluorescent expression effect in the engineered bacteria.Conclusion In this article,antioxidant gene-knockout microbial sensors had been constructed to realize active and sensitive monitoring of DNA damage effects such as DNA damage reagents and UV irradiation.The sensors could provide an active,effective,and sensitive potential monitoring method for future evaluation of radiation effects in space.