Engineering Chimeric Chemoreceptors and Two-Component Systems for Orthogonal and Leakless Biosensing of Extracellular γ-Aminobutyric Acid.

Two-component systems (TCSs) sensing and responding to various stimuli outside and inside cells are valuable resources for developing biosensors with synthetic biology applications. However, the use of TCS-based biosensors suffers from a limited effector spectrum, hypersensitivity, low dynamic range, and unwanted signal crosstalk. Here, we developed a tailor-made Escherichia coli whole-cell γ-aminobutyric acid (GABA) biosensor by engineering a chimeric GABA chemoreceptor PctC and TCS. By testing different TCSs, the chimeric PctC/PhoQ showed the response to GABA. Chimera-directed evolution and introduction of the insulated chimeric pair PctC/PhoQ*PhoP* produced biosensors with up to 3.50-fold dynamic range and good orthogonality. To further enhance the dynamic range and lower the basal leakage, three strategies, engineering of PhoP DNA binding sites, fine-tuning reporter expression by optimizing transcription/translation components, and a tobacco etch virus protease-controlled protein degradation, were integrated. This chimeric biosensor displayed a low basal leakage, a large dynamic range (15.8-fold), and a high threshold level (22.7 g L-1). Finally, the optimized biosensor was successfully applied in the high-throughput microdroplet screening of GABA-overproducing Corynebacterium glutamicum, demonstrating its desired properties for extracellular signal biosensing.

The Impact of Neoadjuvant Chemotherapy on Patients With T1N0M0 Triple-Negative and HER-2 Positive Breast Cancer: A Retrospective Analysis Based on the SEER Database.

BACKGROUND: The utilization of neoadjuvant chemotherapy (NAC) originated in the treatment of locally advanced breast cancer (BC). Our study is designed to elucidate the effects of NAC on patients with T1N0M0 triple-negative and HER-2 positive BC. METHODS: This study involved the selection of 10,614 patients diagnosed with T1N0M0 triple-negative and HER-2 positive breast cancer (BC) from the surveillance, epidemiology, and end results (SEER) database. To ascertain the impact of neoadjuvant chemotherapy (NAC) on T1a, T1b, and T1c N0M0 BC, we conducted multivariate Cox regression analyses. Similarly, we performed multivariate Cox regression analyses to compare the effects of neoadjuvant chemotherapy against adjuvant chemotherapy on T1N0M0 BC. The Kaplan-Meier method was employed to delineate survival curves for different molecular subtypes and clinical stages. RESULTS: The data results from the SEER database reveal a significant enhancement of overall survival (OS) in T1c BC patients as a result of NAC. For T1b BC patients, NAC does not present any significant effect. Contrarily, NAC seems to adversely impact the OS of T1a triple-negative BC patients. However, the prognosis comparison between neoadjuvant and adjuvant chemotherapy for T1N0M0 breast cancer did not show any significant difference, with the exception of T1a triple-negative BC. CONCLUSIONS: Patients with T1cN0M0 triple-negative and HER-2 positive BC may derive OS benefits from NAC. Additionally, NAC could be detrimental to T1a triple-negative BC.

SGMS1 facilitates osteogenic differentiation of MSCs and strengthens osteogenesis-angiogenesis coupling by modulating Cer/PP2A/Akt pathway.

Mesenchymal stem cell (MSC)-mediated coupling of osteogenesis and angiogenesis is a critical phenomenon in bone formation. Herein, we investigated the role and mechanism of SGMS1 in the osteogenic differentiation of MSCs and, in combination with osteogenesis and angiogenesis, to discover new therapeutic targets for skeletal dysplasia and bone defects. SGMS1 addition accelerated MSC osteogenic differentiation, whereas SGMS1 silencing suppressed this process. Moreover, SGMS1 overexpression inhibited ceramide (Cer) and promoted sphingomyelin (SM) levels. SM treatment neutralized the suppressive effect of shSGMS1 on osteogenesis. SGMS1 restrained PP2A activity by regulating Cer/SM metabolism and thus enhanced the levels of phosphorylated Akt, Runx2, and vascular endothelial growth factor (VEGF). Furthermore, SGMS1 transcription was regulated by Runx2. SGMS1 increased MSC-mediated angiogenesis by promoting VEGF expression. SGMS1 addition promoted rat bone regeneration in vivo. In conclusion, SGMS1 induces osteogenic differentiation of MSCs and osteogenic-angiogenic coupling through the regulation of the Cer/PP2A/Akt signaling pathway.

Effect of wound drainage on the wound infection and healing in patients undergoing spinal surgery: A meta-analysis.

A meta-analysis was conducted to comprehensively evaluate the impact of wound drainage on postoperative wound infection and healing in patients undergoing spinal surgery. Computer searches were performed, from database inception to October 2023, in EMBASE, Google Scholar, Cochrane Library, PubMed, Wanfang and China National Knowledge Infrastructure databases for studies related to the application of wound drainage in spinal surgery. Two researchers independently screened the literature, extracted data and conducted quality assessments. Stata 17.0 software was employed for data analysis. Overall, 11 articles involving 2102 spinal surgery patients were included. The analysis showed that, compared to other treatment methods, the use of wound drainage in spinal surgery patients significantly shortened the wound healing time (standardized mean difference [SMD]: -1.35, 95% confidence intervals [CI]: -1.91 to -0.79, p < 0.001). However, there was no statistical difference in the incidence of wound infection (odds ratio: 1.35, 95% CI: 0.83-2.19, p = 0.226). This study indicates that wound drainage in patients undergoing spinal surgery is effective, can accelerate wound healing and is worth promoting in clinical practice.

Prognostic Impact of HER2-Low and HER2-Zero in Resectable Breast Cancer with Different Hormone Receptor Status: A Landmark Analysis of Real-World Data from the National Cancer Center of China.

BACKGROUND: The prognostic impact of HER2-low on overall survival (OS) and disease-free survival (DFS) in patients with resectable breast cancer (BC) remains controversial, partly resulting from the hormone receptor (HR) status. OBJECTIVE: To investigate the prognostic impact of HER2-low in different HR subgroups. PATIENTS AND METHODS: We retrospectively retrieved medical records of treatment-naive primary HER2-low and HER2-zero BC patients who were diagnosed with invasive ductal carcinoma and underwent surgery in the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2009 to September 2017 (n = 7371). We compared the clinicopathologic features and performed Cox regression and landmark survival analyses to explore the prognostic impact of HER2-low on survival outcomes during distinct post-surgery intervals-36 months, 60 months, and 120 months. RESULTS: HER2-low BC, compared to HER2-zero BC, exhibited less aggressive clinicopathologic features, such as smaller invasion size, lower grade, increased nerve invasion, higher HR positivity, and a higher proportion of low-Ki67 cases. In the HR-positive subgroup, HER2-low demonstrated improved OS (p = 0.046) and DFS (p = 0.026) within 60 months. Conversely, HER2-low displayed worse DFS (p = 0.046) in the HR-negative subgroup after 36 months from surgery. The findings remained robust in uni- and multi-variable Cox models. CONCLUSIONS: HER2-low BCs manifested less aggressive clinicopathologic features than the HER2-zero cases. The prognostic impact of HER2-low in resectable BCs exhibits variability contingent upon the patients' HR status.

Revolutionizing the battle against locally advanced breast cancer: A comprehensive insight into neoadjuvant radiotherapy.

Breast cancer (BC) constitutes one of the most pervasive malignancies affecting the female population. Despite progressive improvements in diagnostic and therapeutic technologies, leading to an increased detection of early stage BCs, locally advanced breast cancer (LABC) persists as a significant clinical challenge. Owing to its poor overall survival (OS) rate, elevated recurrence rate, and high potential for distant metastasis, LABC prominently impacts the comprehensive efficacy of BC treatments. Radiotherapy, encompassing preoperative, intraoperative, and postoperative modalities, is acknowledged as an effective strategy for mitigating BC metastasis and enhancing survival rates among patients. Nevertheless, the domain of preoperative neoadjuvant radiotherapy (NART) remains conspicuously underexplored in clinical studies. Available research suggests that NART can induce tumor volume reduction, provoke fibrotic changes in tumor and adjacent normal tissues, thereby mitigating intraoperative cancer propagation and enhancing the quality of life for LABC patients. This manuscript seeks to provide a review of contemporary research pertaining to LABC and its preoperative radiotherapy.

Antioxidant peptides, the guardian of life from oxidative stress.

Reactive oxygen species (ROS) are produced during oxidative metabolism in aerobic organisms. Under normal conditions, ROS production and elimination are in a relatively balanced state. However, under internal or external environmental stress, such as high glucose levels or UV radiation, ROS production can increase significantly, leading to oxidative stress. Excess ROS production not only damages biomolecules but is also closely associated with the pathogenesis of many diseases, such as skin photoaging, diabetes, and cancer. Antioxidant peptides (AOPs) are naturally occurring or artificially designed peptides that can reduce the levels of ROS and other pro-oxidants, thus showing great potential in the treatment of oxidative stress-related diseases. In this review, we discussed ROS production and its role in inducing oxidative stress-related diseases in humans. Additionally, we discussed the sources, mechanism of action, and evaluation methods of AOPs and provided directions for future studies on AOPs.

Occult breast cancer patients with mastectomy have better prognosis than those with breast-conserving therapy.

Background: This single-center retrospective study compared the efficacy of breast-conserving therapy along with axillary lymph node dissection (ALND) with mastectomy and ALND with regard to survival of Chinese patients with occult breast cancer. Materials & methods: Univariate Kaplan-Meier analysis and multivariate Cox proportional hazards model were used to compare treatments and prognosis. Results: A total of 111 patients with a median follow-up of 72.9 months were included. 39 patients with mastectomy + ALND had better disease-free survival than 72 patients with breast-conserving therapy + ALND (HR = 0.31; p = 0.012). Patients with radiotherapy demonstrated inferior survival for both overall survival (HR = 2.67; p = 0.071) and disease-free survival (HR = 5.35; p = 0.002). Surgical strategies and radiotherapy remained significantly predictive of better disease-free survival in multivariate analyses. Conclusion: Mastectomy and ALND demonstrate superior disease-free prognosis compared with breast-conserving therapy and ALND in occult breast cancer.

Antimicrobial, antioxidant, anti-inflammatory, and cytotoxic activities of Cordyceps militaris spent substrate.

Cordyceps militaris is a medicinal mushroom and has been extensively used as a traditional medicine in East Asia. After the chrysalis seeds are matured and harvested, the spent substrate of C. militaris still contains active ingredients but is usually discarded as waste. This study aimed to determine the antioxidant and anti-inflammatory activities of C. militaris spent substrate extract and its inhibitory activity on the Malassezia commensal yeasts that can cause dandruff and seborrheic dermatitis. Active substances in the spent substrate of C. militaris were extracted using a hot water extraction method and were used for the determination of antioxidant activity by measuring their ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl radicals, hydrogen peroxide, and superoxide anions. The ability to inhibit Malassezia was analyzed using the broth microdilution method, and the reparative effect on oxidative damage in HaCaT cells was measured using in vitro cell analysis. Respiratory burst evaluation was used to determine the anti-inflammatory capacity of extracts. Analysis of the Malassezia-inhibiting activity of the extracts showed that the minimum inhibitory concentration was 6.25 mg/mL. The half maximal inhibitory concentration (IC50) values of DPPH, O2-, H2O2 and OH- were 3.845 mg/mL, 2.673 mg/mL, 0.037 mg/mL and 0.046 mg/mL, respectively. In the concentration range of 2 to 50%, the extract was non-toxic to cells and was able to protect HaCaT cells from H2O2 damage. When the volume fraction of the extract was 20.96%, its anti-inflammatory ability reached 50%. These results demonstrated that the extract may be a safe and efficacious source for pharmaceutical or cosmetic applications, with Malassezia-inhibiting, antioxidant and anti-inflammatory activities.

Identifying clinicopathological risk factors for regional lymph node metastasis in Chinese patients with T1 breast cancer: a population-based study.

Objectives: To analyze clinicopathological risk factors and regular pattern of regional lymph node metastasis (LNM) in Chinese patients with T1 breast cancer and the effect on overall survival (OS) and disease-free survival (DFS). Materials and methods: Between 1999 and 2020, breast cancer patients meeting inclusion criteria of unilateral, no distant metastatic site, and T1 invasive ductal carcinoma were reviewed. Clinical pathology characteristics were retrieved from medical records. Survival analysis was performed using Kaplan-Meier methods and an adjusted Cox proportional hazards model. Results: We enrolled 11,407 eligible patients as a discovery cohort to explore risk factors for LNM and 3484 patients with stage T1N0 as a survival analysis cohort to identify the effect of those risk factors on OS and DFS. Compared with patients with N- status, patients with N+ status had a younger age, larger tumor size, higher Ki67 level, higher grade, higher HR+ and HER2+ percentages, and higher luminal B and HER2-positive subtype percentages. Logistic regression indicated that age was a protective factor and tumor size/higher grade/HR+ and HER2+ risk factors for LNM. Compared with limited LNM (N1) patients, extensive LNM (N2/3) patients had larger tumor sizes, higher Ki67 levels, higher grades, higher HR- and HER2+ percentages, and lower luminal A subtype percentages. Logistic regression indicated that HR+ was a protective factor and tumor size/higher grade/HER2+ risk factors for extensive LNM. Kaplan-Meier analysis indicated that grade was a predictor of both OS and DFS; HR was a predictor of OS but not DFS. Multivariate survival analysis using the Cox regression model demonstrated age and Ki67 level to be predictors of OS and grade and HER2 status of DFS in stage T1N0 patients. Conclusion: In T1 breast cancer patients, there were several differences between N- and N+ patients, limited LNM and extensive LNM patients. Besides, HR+ plays a dual role in regional LNM. In patients without LNM, age and Ki67 level are predictors of OS, and grade and HER2 are predictors of DFS.

Clinical Features and Prognoses of Patients With Breast Cancer Who Underwent Surgery.

Importance: Breast cancer (BC) remains a pervasive malignant neoplasm worldwide, with increasing incidence. However, there are a scarcity of studies examining the clinical characteristics and prognosis of Chinese patients with BC who have undergone surgery. Objective: To evaluate overall survival (OS) and disease-free survival (DFS) in patients with surgically treated BC in China, focusing on histopathology and surgical approach. Design, Setting, and Participants: This cohort study included a retrospective review of the medical records of patients with unilateral BC who underwent surgery between January 2009 and September 2017, with a median follow-up time of 7.69 years. Clinical features were extracted from these records, and survival analysis was performed. Data analysis was conducted in March 2023. Main Outcomes and Measures: Patients' OS and DFS. Results: The study included 14 782 patients (14 724 [99.6%] female patients; mean [SD] age, 51.6 [10.9] years). Invasive ductal carcinoma (IDC) was the most prevalent type, observed in 12 671 patients (85.6%). Stages 0, I, II, III, and IV accounted for 6.4% (919 patients), 32.0% (4579 patients), 40.5% (5791 patients), 20.2% (2896 patients), and 0.9% (126 patients) of cases, respectively. Hormone receptor (HR) positivity was observed in 10 241 patients (75.1%), and 3665 (29.1%) tested positive for ERBB2 (formerly HER2/neu). The HR-negative-ERBB2-negative, HR-negative-ERBB2-positive, HR-positive-ERBB2-negative, and HR-positive-ERBB2-positive subtypes constituted 13.3% (1666 patients), 12.7% (1595 patients), 57.8% (7251 patients), and 16.2% (2034 patients) of cases, respectively. Breast-conserving surgery (BCS) was performed in 2884 patients (19.5%). The 5-year and 10-year OS rates were 92.9% (13 689 of 14 732) and 87.4% (3287 of 3760), while the 5-year and 10-year DFS rates were 89.0% (12 916 of 14 512) and 82.9% (3078 of 3713), respectively. Multivariate analysis found that for patients with IDC, age, BCS, invasive tumor size, tumor grade, lymphovascular invasion (LVI), the number of lymph node metastases (LNMs), distant metastasis, Ki67, and HR status were associated with OS, whereas invasive tumor size, tumor grade, LVI, the number of LNMs, HR status, and ERBB2 status were associated with DFS. After propensity score matching, BCS was equivalent to mastectomy with respect to survival in patients with IDC. Conclusions and Relevance: This cohort study of patients with BC who underwent surgery in China provides valuable insights into the histopathological characteristics and survival outcomes of this population. The diverse histopathological features emphasize the necessity for customized treatment strategies. The relatively low BCS rate in the study population suggests the need for heightened awareness and adoption of this approach, considering its potential advantages for survival.

Atopic dermatitis and risk of 14 site-specific cancers: A Mendelian randomization study.

BACKGROUND: Atopic dermatitis (AD) accounts for a large proportion of the burden of skin disease, with a prevalence of around 10% among adults worldwide. In addition, systematic reviews and meta-analyses have found that AD is associated with cancer risk at several sites; if found to be causal this could highlight potential treatment targets to reduce cancer risk. OBJECTIVES: To assess the potential causative link between AD and 14 site-specific cancers in a two-sample randomization study. METHODS: From the largest genome-wide association study (GWAS) of AD (10,788 cases and 30,047 non-cases), genetic variants highly associated (p < 5 × 10-8 ) with AD in the European population were selected as instrumental variables (IVs). Data from large cancer consortia, as well as the UK Biobank study (n = 442,239) and the FinnGen study (n = 218,792), were employed to assess genetic associations with 14 site-specific cancers and overall cancer. A set of complementary approaches and sensitivity analyses were carried out to examine the robustness of our results. In addition, associations for the same cancer site from different data sources were combined using meta-analyses. RESULTS: We discovered no strong causal evidence of AD on the risk of overall cancer, with effect estimates close to zero. After the Benjamini-Hochberg correction, the inverse-variance weighted method indicated no association between AD and overall cancer risk in both the UK Biobank (OR, 1.00; 95% CI, 0.94-1.06; FDR, 0.98) and FinnGen studies (OR, 0.96; 95% CI, 0.92-1.02; FDR, 0.68). No strong evidence of an association was found between genetically predicted AD and the risk of any site-specific cancers. CONCLUSIONS: Our MR investigation does not support a causal effect of AD on cancer risk. This finding has important implications for the prevention and management of both AD and cancer, as it reduces the concern of potential adverse effects of AD on cancer outcomes.

Probiotics formulation and cancer nanovaccines show synergistic effect in immunotherapy and prevention of colon cancer.

Probiotics play essential roles in immune modulation. Combining probiotics with cancer vaccines potentially can achieve a synergistic effect. To maximize the efficacy of probiotics, proper probiotics formulation is necessary. Herein, Lactobacillus rhamnosus and Bifidobacterium longum are coated with lipid membrane to achieve the goal of losing less activity and bettering colonization in colon. In the subcutaneous transplanted colon cancer mouse model, probiotics formulation showed potent preventive and therapeutic efficacy, and the efficacy could be further improved by combining with cancer nanovaccines. Probiotics formulation can perform as immune adjuvants to enhance the innate immune response or as in-situ cancer vaccines. In the study of preventing chemical-induced orthotopic colon cancer model, probiotics formulation alone efficiently reduced tumor number in colon and the efficacy is improved by combining with cancer nanovaccines. All in all, the studies demonstrated that probiotics formulation can assist to maximize the efficacy of cancer nanovaccines.

Risk of cerebrovascular disease after cancer diagnosis in the United States.

The risk of subsequent cerebrovascular disease among cancer patients of multiple cancers in the US is not well understood. A total of 3,843,261 cancer patients diagnosed from 1975 to 2018, were included from the surveillance, epidemiology, and end results (SEER) database. Standardized mortality ratios (SMRs) and absolute excess risks (AERs) were estimated. The overall cerebrovascular disease SMR was 1.04 (95% CI, 1.03-1.04), and the AER per 10,000 person-years at risk was 0.89. When compared with the US general population, greater cerebrovascular disease risk was correlated with certain cancer sites, American Indian/Alaska Native race, Asian or Pacific Islander race, unmarried marital status, distant metastasis, younger age, and an earlier time of cancer diagnosis. Clinically, more precision and proactive strategies for cerebrovascular disease prevention are required to subgroup of cancer patients with a greater risk of cerebrovascular disease, especially within the first two months.

How Alligator Immune Peptides Kill Gram-Negative Bacteria: A Lipid-Scrambling, Squeezing, and Extracting Mechanism Revealed by Theoretical Simulations.

Alligator sinensis cathelicidins (As-CATHs) are antimicrobial peptides extracted from alligators that enable alligators to cope with diseases caused by bacterial infections. This study assessed the damaging effects of sequence-truncated and residue-substituted variants of As-CATH4, AS4-1, AS4-5, and AS4-9 (with decreasing charges but increasing hydrophobicity) on the membranes of Gram-negative bacteria at the molecular level by using coarse-grained molecular dynamics simulations. The simulations predicted that all the variants disrupt the structures of the inner membrane of Gram-negative bacteria, with AS4-9 having the highest antibacterial activity that is able to squeeze the membrane and extract lipids from the membrane. However, none of them can disrupt the structure of asymmetric outer membrane of Gram-negative bacteria, which is composed of lipopolysaccharides in the outer leaflet and phospholipids in the inner leaflet. Nonetheless, the adsorption of AS4-9 induces lipid scrambling in the membrane by lowering the free energy of a phospholipid flipping from the inner leaflet up to the outer leaflet. Upon binding onto the lipid-scrambled outer membrane, AS4-9s are predicted to squeeze and extract phospholipids from the membrane, AS4-5s have a weak pull-out effect, and AS4-1s mainly stay free in water without any lipid-extracting function. These findings provide inspiration for the development of potent therapeutic agents targeting bacteria.

Effect of offset on the precision of 3D-printed orthognathic surgical splints.

OBJECTIVE: This study evaluated the effect of offset on the precision of three-dimensional (3D)-printed splints, proposing to optimize the splint design to compensate for systematic errors. MATERIALS AND METHODS: 14 resin model sets were scanned and offset as a whole by given distances (0.05, 0.10, 0.15, 0.20, 0.25, 0.30, 0.35, and 0.40 mm). Intermediate splints (ISs) and final splints (FSs) were generated from the non-offset and offset models and grouped correspondingly, named as splint type-offset value, IS-0.05, for instance. Dentitions occluded with the splint were scanned. Translational and rotational deviations of the lower dentition relative to the upper dentition were 3D measured. RESULTS: Deviations of ISs and FSs were more evident in the vertical and pitch dimensions, and were mostly acceptable in other dimensions. ISs with offset ≥ 0.05 mm showed vertical deviations significantly below 1 mm (P < 0.05) while ISs with 0.10- to 0.30-mm offsets had pitch rotations significantly lower than 1° (P < 0.05). The Pitch of IS-0.35 was significantly larger than ISs with 0.15- to 0.30-mm offsets (P < 0.05). Meanwhile, FSs fit better as the offset increased and FSs with offsets ≥ 0.15 mm all had deviations significantly lower than 1 mm (for translation) or 1° (for rotation) (P < 0.05). CONCLUSIONS: Offset affects the precision of 3D-printed splints. Moderate offset values of 0.10 to 0.30 mm are recommendable for ISs. Offset values ≥ 0.15 mm are recommended for FSs in cases with stable final occlusion. CLINICAL RELEVANCE: This study found the optimal offset ranges for 3D-printed ISs and FSs via a standardized protocol.

The association between penicillin allergy and surgical site infection after orthopedic surgeries: a retrospective cohort study.

Background: Cephalosporins are used as first-line antimicrobial prophylaxis for orthopedics surgeries. However, alternative antibiotics are usually used in the presence of penicillin allergy (PA), which might increase the risk of surgical site infection (SSI). This study aimed to analyze the relationship between SSI after orthopedic surgeries and PA among surgical candidates and related alternative antibiotic use. Methods: In this single-center retrospective cohort study, we compared inpatients with and without PA from January 2015 to December 2021. The primary outcome was SSI, and the secondary outcomes were SSI sites and perioperative antibiotic use. Moreover, pathogen characteristics of all SSIs were also compared between the two cohorts. Results: Among the 20,022 inpatient records, 1704 (8.51%) were identified with PA, and a total of 111 (0.55%) SSI incidents were reported. Compared to patients without PA, patients with PA had higher postoperative SSI risk (1.06%, 18/1704 vs. 0.51%, 93/18318), shown both in multivariable regression analysis (odds ratio [OR] 2.11; 95% confidence interval [CI], 1.26-3.50; p= 0.004) and propensity score matching (OR 1.84; 95% CI, 1.05-3.23; p= 0.034). PA was related to elevated deep SSI risk (OR 2.79; 95% CI, 1.47-5.30; p= 0.002) and had no significant impact on superficial SSI (OR 1.39; 95% CI, 0.59-3.29; p= 0.449). The PA group used significantly more alternative antibiotics. Complete mediation effect of alternative antibiotics on SSI among these patients was found in mediation analysis. Pathogen analysis revealed gram-positive cocci as the most common pathogen for SSI in our study cohort, while patients with PA had higher infection rate from gram-positive rods and gram-negative rods than non-PA group. Conclusion: Compared to patients without PA, patients with PA developed more SSI after orthopedic surgeries, especially deep SSI. The elevated infection rate could be secondary to the use of alternative prophylactic antibiotics.

Rationally Designed Nonapeptides with Great Skin Photoprotective Effect through Producing Type 1 Collagen and Blocking the mTOR Pathway.

Ultraviolet (UV), as the most common environmental stress factor to human skin, causes redox imbalance and leads to photoaging and the development of cancer. In this work, we screened a nonapeptide (PWH) with good activities of antioxidant, promoting the secretion of type 1 collagen (COL-1) and repairing damaged skin from a series of rationally designed novel short peptides. PWH could alleviate UV-A-induced oxidative stress, restrain pro-inflammatory cytokine production, protect mitochondrial function, and maintain autophagy activity. We also first indicated that inhibiting the PI3K/AKT/mTOR signaling pathway and restoration of autophagy activity might delay the photoaging process in skin cells. Topical applications of PWH were further demonstrated to exhibit significant protection in full-wavelength UV-induced skin aging in mice models both in the prophylaxis and treatment way. In addition, given the good stability and without unwanted toxicity and anaphylaxis, PWH could be a promising candidate for cosmetics and pharmaceuticals.

A novel feedback regulated loop of circRRM2-IGF2BP1-MYC promotes breast cancer metastasis.

BACKGROUND: Metastasis is the leading cause of mortality in patients with breast cancer (BC). Studies demonstrate that circular RNAs (circRNAs) were involved in BC progression, while the molecular mechanisms remain largely unclear. METHODS: The microArray circRNA profiles were used to explore the differential expression circRNAs in BC and paracancerous normal tissues, and the quantitative reverse transcription-polymerase chain reaction was used to validate their expression level in clinical samples and cell lines. Nuclear/cytosolic fractionation and fluorescence in situ hybridization (FISH) assays were performed to examine circRRM2 (hsa_circ_0052582) subcellular location. The scratch wound healing and transwell assays were conducted to evaluate the impact of circRRM2 on BC cell migration and invasion. We predicted miRNAs that might bind with cricRRM2 and the downstream target genes using bioinformatics analysis and explored their expression levels and prognostic value in BC. FISH, RNA immunoprecipitation, Co-immunoprecipitation, Western blot, and rescue experiments were implemented to figure out circRRM2 function and underlying mechanisms in BC. RESULTS: The present study revealed several aberrant circRNAs in BC tissues and observed that circRRM2 was upregulated in tumor tissues of 40 patients with BC. High circRRM2 was significantly associated with advanced N stage in patients with BC. Gain- and loss- of function experiments revealed that circRRM2 promoted the migration and invasion of cells and functioned as an oncogene in BC. Mechanism studies showed that circRRM2 competed with miR-31-5p/miR-27b-3p to upregulate the IGF2BP1 expression. Furthermore, IGF2BP1 upregulated the circRRM2 level via interacting with MYC, which functioned as the transcriptional factor of circRRM2. Thus, the positive feedback loop that was composed of circRRM2/IGF2BP1/MYC was identified. CONCLUSION: This study confirms that upregulated circRRM2 functions an oncogenic role in BC metastasis. The positive feedback loop of circRRM2/IGF2BP1/MYC enforces the circRRM2 expression, which might offer a potential target for BC treatment.

Preparation of Functionalized Zr-Based MOFs and MOFs/GO for Efficient Removal of 1,3-Butadiene from Cigarette Smoke.

Removal of 1,3-butadiene from cigarette smoke plays an important role in human health and environmental protection. Herein, a series of UiO-66 X% containing different ratios of the -NH2 group was synthesized via the solvothermal method by using terephthalic acid (H2BDC) and 2-aminoterephthalic acid (NH2-BDC) as ligands. Using GO as support, a series of UiO-66-NH2/GO Y% were prepared by controlling the ratio of UiO-66-NH2 and GO. The effects of -NH2 and GO contents on the structure and composition of MOFs were investigated. Finally, the different -NH2 contents of UiO-66 X% and the different GO contents of UiO-66-NH2/GO Y% were applied in 1,3-butadiene removal from cigarette smoke. The results showed that UiO-66 X% with the higher contents of -NH2 showed a higher rate of 1,3-butadiene removal, and UiO-66-NH2/GO Y% with the GO contents of 5% showed the highest removal rate of about 33.85%, which was 25.54% higher than that of activated carbon. In addition, the saturation capacity of the adsorbent materials for 1,3-butadiene was as high as 210.01-239.54 mg/g, showing great potential in reducing harmful components in cigarette smoke and environmental protection.