How does China's green credit policy affect the innovation of high-polluting enterprises? From the perspective of innovation quantity and quality.

Employing the "Green Credit Guidelines" implemented in 2012 as the basis for a quasi-natural experiment, this study applies the method of Difference-in-Differences(DID) to investigate the influence of the Green Credit Policy on both the quantity and quality of enterprise innovation. The outcomes of our analysis reveal that the policy has significantly boosted both the quantity and quality of innovation among enterprises identified as heavy polluters. It is noteworthy that the policy's positive impact on innovation quantity surpasses its positive effect on innovation quality. This substantiates that the Green Credit Policy effectively generates incentivizing outcomes for innovation among the heavy polluters, thereby verifying Porter's hypothesis within the domain of green credit in China. Furthermore, we find that the positive impact is more significant for enterprises with lower innovation capabilities, large-scale enterprises, state-owned enterprises, and those situated in both the Eastern and Western regions. Through these findings, this study illuminates a novel perspective on the interplay between the Green Credit Policy and enterprise innovation dynamics in China.

Optimal Glycated Hemoglobin Cutoff for Diagnosis of Diabetes and Prediabetes in Chinese Breast Cancer Women.

Purpose: Glycated hemoglobin (HbA1c) is widely used in diabetes management and now recommended for diagnosis and risk assessment. Our research focused on investigating the optimal cutoff points of HbA1c for diagnosis of diabetes and prediabetes in Chinese breast cancer women, aiming to enhance early detection and tailor treatment strategies. Patients and Methods: This study involved 309 breast cancer women without diabetes history in China. Patients were categorized into groups of newly diagnosed diabetes, prediabetes, and normal glucose tolerance using oral glucose tolerance test (OGTT) according to the 2010 ADA criteria. HbA1c data were collected from all patients. Receiver operating characteristic (ROC) curve analysis was used to assess the effectiveness of the HbA1c screening. Results: Among the 309 breast cancer women without diabetes history, 96 (31.0%) were identified with diabetes and 130 (42.1%) had prediabetes according to OGTT, and the incidence of normal glucose tolerance was only 26.9% (83). ROC curve analysis, using OGTT as a reference, revealed that the area under the curve of 0.903 (P<0.001, 95% CI, 0.867-0.938) for HbA1c alone, indicating high accuracy. The optimal HbA1c cutoff for identifying diabetes was determined to be 6.0%, with a sensitivity of 78.1% and specificity of 86.4%. For prediabetes, the ROC curve for HbA1c alone showed that the area under the ROC curve of 0.703 (P<0.001, 95% CI, 0.632-0.774), with an optimal cutoff of 5.5% (sensitivity of 76.9% and specificity of 51.8%). Conclusion: The prevalence of undiagnosed diabetes is very high in breast cancer women without diabetes history in China. The optimal cutoff points of HbA1c for identifying diabetes and prediabetes are 6.0% and 5.5% in Chinese breast cancer women, respectively.

Tuning Surface Organic Structures by Small Gas Molecules through Catassembly and Coassembly.

The field of molecular assembly has seen remarkable advancements across various domains, such as materials science, nanotechnology, and biomedicine. Small gas molecules serve as pivotal modulators, capable of altering the architecture of assemblies via tuning a spectrum of intermolecular forces including hydrogen bonding, dipole-dipole interactions, and metal coordination. Surface techniques, notably scanning tunneling microscopy and atomic force microscopy, have proven instrumental in dissecting the structural metamorphosis and characteristic features of these assemblies at an unparalleled single-molecule resolution. Recent research has spotlighted two innovative approaches for modulating surface molecular assemblies with the aid of small gas molecules: "catassembly" and "coassembly". This Perspective delves into these methodologies through the lens of varying molecular interaction types. The strategies discussed here for regulating molecular assembly structures using small gas molecules can aid in understanding various complex assembly processes and structures and provide guidance for the further fabrication of complex surface structures.

Mechanisms of ligand recognition and activation of melanin-concentrating hormone receptors.

Melanin-concentrating hormone (MCH) is a cyclic neuropeptide that regulates food intake, energy balance, and other physiological functions by stimulating MCHR1 and MCHR2 receptors, both of which are class A G protein-coupled receptors. MCHR1 predominately couples to inhibitory G protein, Gi/o, and MCHR2 can only couple to Gq/11. Here we present cryo-electron microscopy structures of MCH-activated MCHR1 with Gi and MCH-activated MCHR2 with Gq at the global resolutions of 3.01 Å and 2.40 Å, respectively. These structures reveal that MCH adopts a consistent cysteine-mediated hairpin loop configuration when bound to both receptors. A central arginine from the LGRVY core motif between the two cysteines of MCH penetrates deeply into the transmembrane pocket, triggering receptor activation. Integrated with mutational and functional insights, our findings elucidate the molecular underpinnings of ligand recognition and MCH receptor activation and offer a structural foundation for targeted drug design.

Dynamic effective connectivity in the cerebellar dorsal dentate nucleus and the cerebrum, cognitive impairment, and clinical correlates in patients with schizophrenia.

BACKGROUND: Schizophrenia (SZ) is characterized by disconnected cerebral networks. Recent studies have shown that functional connectivity between the cerebellar dorsal dentate nucleus (dDN) and cerebrum is correlated with psychotic symptoms, and processing speed in SZ patients. Dynamic effective connectivity (dEC) is a reliable indicator of brain functional status. However, the dEC between the dDN and cerebrum in patients with SZ remains largely unknown. METHODS: Resting-state functional MRI data, symptom severity, and cognitive performance were collected from 74 SZ patients and 53 healthy controls (HC). Granger causality analysis and sliding time window methods were used to calculate dDN-based dEC maps for all subjects, and k-means clustering was performed to obtain several dEC states. Finally, between-group differences in dynamic effective connectivity variability (dECV) and clinical correlations were obtained using two-sample t-tests and correlation analysis. RESULTS: We detected four dEC states from the cerebrum to the right dDN (IN states) and three dEC states from the right dDN to the cerebrum (OUT states), with SZ group having fewer transitions in the OUT states. SZ group had increased dECV from the right dDN to the right middle frontal gyrus (MFG) and left lingual gyrus (LG). Correlations were found between the dECV from the right dDN to the right MFG and symptom severity and between the dECV from the right dDN to the left LG and working memory performance. CONCLUSIONS: This study reveals a dynamic causal relationship between cerebellar dDN and the cerebrum in SZ and provides new evidence for the involvement of cerebellar neural circuits in neurocognitive functions in SZ.

Case report and literature review: Asymptomatic littoral cell angioma in a 3-year-old girl.

Background: Littoral cell angioma (LCA) is an extremely uncommon benign vascular tumor of the spleen. Cases of LCA in infants are rarely reported, and due to the rarity of the tumor and non-specific symptoms, the diagnosis of LCA is often overlooked in clinical practice. Case report: We present a 3-year-old girl with pulmonary inflammation who was admitted to the hospital due to the discovery of a space-occupying lesion in the spleen. Pathology after splenectomy confirmed LCA, and there was no recurrence observed at the 5-month follow-up examination. Conclusion: LCA should be considered when a child shows asymptomatic splenomegaly, with antigen expression indicating dual positivity of endothelial and histiocytic markers. Laparoscopic splenectomy remains the primary method of treating LCA.

Probiotic Compounds Enhanced Recovery after Surgery for Patients with Distal Gastric Cancer: A Prospective, Controlled Clinical Trial.

BACKGROUND: Enhanced recovery after surgery (ERAS) for radical distal gastrectomy needs to be improved urgently. We investigated the effects of probiotic compounds (including Lactobacillus plantarum, L. rhamnosus, L. acidophilus, and Bifidobacterium animalis subsp.lactis) on enhance recovery after gastrectomy. METHODS: The patients in this prospective study were divided into probiotic group (PG group, n = 36) and placebo group (CG group, n = 38), taking corresponding capsule according to the protocol during the perioperative period. We compared the trends in perioperative hematologic findings and the postoperative outcomes. Patients' feces were collected for bacterial 16S rRNA sequencing. Patients were followed up at 1 month postoperatively. RESULTS: After the application of probiotics, the patients' postoperative inflammatory response level was reduced, and the trend of postoperative NLR decrease was significantly faster in the patients of the PG group than in the CG group (P = 0.047, partial η2 = 0.054). The trend of postoperative increase in serum albumin concentration in the patients of the PG group was significantly better than that in the CG group (P = 0.016, partial η2 = 0.078). In addition, patients in the PG group met discharge criteria earlier postoperatively and had fewer medical expenses. The quality of life of PG group was improved postoperatively. Postoperative inflammation-related markers, including the ratio of Firmicutes/Bacteroidetes, were increasing in untreated patients. In addition, the postoperative microbial diversity and abundance in the PG group remained stable. CONCLUSIONS: Probiotic compounds can reduce the inflammatory response after gastrectomy and enhance the recovery of the DGC patients by maintaining the stability of the gut microbiota.

Enhancing pneumonia prognosis in the emergency department: a novel machine learning approach using complete blood count and differential leukocyte count combined with CURB-65 score.

BACKGROUND: Pneumonia poses a major global health challenge, necessitating accurate severity assessment tools. However, conventional scoring systems such as CURB-65 have inherent limitations. Machine learning (ML) offers a promising approach for prediction. We previously introduced the Blood Culture Prediction Index (BCPI) model, leveraging solely on complete blood count (CBC) and differential leukocyte count (DC), demonstrating its effectiveness in predicting bacteremia. Nevertheless, its potential in assessing pneumonia remains unexplored. Therefore, this study aims to compare the effectiveness of BCPI and CURB-65 in assessing pneumonia severity in an emergency department (ED) setting and develop an integrated ML model to enhance efficiency. METHODS: This retrospective study was conducted at a 3400-bed tertiary medical center in Taiwan. Data from 9,352 patients with pneumonia in the ED between 2019 and 2021 were analyzed in this study. We utilized the BCPI model, which was trained on CBC/DC data, and computed CURB-65 scores for each patient to compare their prognosis prediction capabilities. Subsequently, we developed a novel Cox regression model to predict in-hospital mortality, integrating the BCPI model and CURB-65 scores, aiming to assess whether this integration enhances predictive performance. RESULTS: The predictive performance of the BCPI model and CURB-65 score for the 30-day mortality rate in ED patients and the in-hospital mortality rate among admitted patients was comparable across all risk categories. However, the Cox regression model demonstrated an improved area under the ROC curve (AUC) of 0.713 than that of CURB-65 (0.668) for in-hospital mortality (p<0.001). In the lowest risk group (CURB-65=0), the Cox regression model outperformed CURB-65, with a significantly lower mortality rate (2.9% vs. 7.7%, p<0.001). CONCLUSIONS: The BCPI model, constructed using CBC/DC data and ML techniques, performs comparably to the widely utilized CURB-65 in predicting outcomes for patients with pneumonia in the ED. Furthermore, by integrating the CURB-65 score and BCPI model into a Cox regression model, we demonstrated improved prediction capabilities, particularly for low-risk patients. Given its simple parameters and easy training process, the Cox regression model may be a more effective prediction tool for classifying patients with pneumonia in the emergency room.

Regioselective hydroformylation of propene catalysed by rhodium-zeolite.

Hydroformylation is an industrial process for the production of aldehydes from alkenes1,2. Regioselective hydroformylation of propene to high-value n-butanal is particularly important, owing to a wide range of bulk applications of n-butanal in the manufacture of various necessities in human daily life3. Supported rhodium (Rh) hydroformylation catalysts, which often excel in catalyst recyclability, ease of separation and adaptability for continuous-flow processes, have been greatly exploited4. Nonetheless, they usually consist of rotationally flexible and sterically unconstrained Rh hydride dicarbonyl centres, only affording limited regioselectivity to n-butanal5-8. Here we show that proper encapsulation of Rh species comprising Rh(I)-gem-dicarbonyl centres within a MEL zeolite framework allows the breaking of the above model. The optimized catalyst exhibits more than 99% regioselectivity to n-butanal and more than 99% selectivity to aldehydes at a product formation turnover frequency (TOF) of 6,500 h-1, surpassing the performance of all heterogeneous and most homogeneous catalysts developed so far. Our comprehensive studies show that the zeolite framework can act as a scaffold to steer the reaction pathway of the intermediates confined in the space between the zeolite framework and Rh centres towards the exclusive formation of n-butanal.

Enhancing biomass and lipid accumulation by a novel microalga for unsterilized piggery biogas slurry remediation.

The cost and efficiency of an algal-BS treatment system are determined by the specific microalgal species and BS pretreatment method. This study examines the growth of a novel algae Chlorella sp. YSD-2 and the removal of nutrients from the BS using different pretreatment methods, including dilution ratio and sterilization. The highest biomass production (1.84 g L-1) was achieved in the 1:2 unsterilized biogas slurry, which was 2.03 times higher than that in the sterilized group, as well as higher lipid productivity (17.29 mg L-1 d-1). Nevertheless, the sterilized biogas slurry at a 1:1 dilution ratio exhibited the most notable nutrient-removal efficiency, with COD at 71.97%, TP at 91.32%, and TN at 88.80%. Additionally, the analysis of 16S rRNA sequencing revealed a significant alteration in the indigenous bacterial composition of the biogas slurry by microalgal treatment, with Proteobacteria and Cyanobacteria emerging as the predominant phyla, and unidentified_Cyanobacteria as the primary genus. These findings suggest that Chlorella sp. YSD-2 exhibits favorable tolerance and nutrient-removal capabilities in unsterilized, high-strength biogas slurry, along with high productivity of biomass and lipids. Consequently, these results offer a theoretical foundation for the development of an efficient and economically viable treatment method for algal-BS.

Selective Cleavage of α-Olefins to Produce Acetylene and Hydrogen.

Acetylene production from mixed α-olefins emerges as a potentially green and energy-efficient approach with significant scientific value in the selective cleavage of C-C bonds. On the Pd(100) surface, it is experimentally revealed that C2 to C4 α-olefins undergo selective thermal cleavage to form surface acetylene and hydrogen. The high selectivity toward acetylene is attributed to the 4-fold hollow sites which are adept at severing the terminal double bonds in α-olefins to produce acetylene. A challenge arises, however, because acetylene tends to stay at the Pd(100) surface. By using the surface alloying methodology with alien Au, the surface Pd d-band center has been successfully shifted away from the Fermi level to release surface-generated acetylene from α-olefins as a gaseous product. Our study actually provides a technological strategy to economically produce acetylene and hydrogen from α-olefins.

Targeted inhibition of the PI3K/AKT/mTOR pathway by (+)-anthrabenzoxocinone induces cell cycle arrest, apoptosis, and autophagy in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC), characterized by low survival rates and a high recurrence rate, is a major cause of cancer-related mortality. Aberrant activation of the PI3K/AKT/mTOR signaling pathway is a common driver of NSCLC. Within this study, the inhibitory activity of (+)-anthrabenzoxocinone ((+)-ABX), an oxygenated anthrabenzoxocinone compound derived from Streptomyces, against NSCLC is demonstrated for the first time both in vitro and in vivo. Mechanistically, it is confirmed that the PI3K/AKT/mTOR signaling pathway is targeted and suppressed by (+)-ABX, resulting in the induction of S and G2/M phase arrest, apoptosis, and autophagy in NSCLC cells. Additionally, the augmentation of intracellular ROS levels by (+)-ABX is revealed, further contributing to the inhibition of the signaling pathway and exerting inhibitory effects on tumor growth. The findings presented in this study suggest that (+)-ABX possesses the potential to serve as a lead compound for the treatment of NSCLC.

Hydroxychloroquine-induced hyperpigmentation of the skin and bull's-eye maculopathy in rheumatic patients: a case report and literature review.

Hydroxychloroquine (HCQ) is used as a traditional disease-modifying antirheumatic drugs (DMARDs), for the treatment of autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, it can cause serious adverse reactions, including hyperpigmentation of the skin and bull's-eye macular lesions. Here, we present a case of HCQ-induced hyperpigmentation of the skin and bull's-eye macular lesions in a patient who received HCQ for RA. A 65-year-old female patient developed blurred vision and hyperpigmentation of multiple areas of skin over the body for one month after 3 years of HCQ treatment for RA. Based on clinical presentation, ophthalmological examination and dermatopathological biopsy, a diagnosis of drug-induced cutaneous hyperpigmentation and bullous maculopathy of the right eye was made. After discontinuation of HCQ and treatment with iguratimod tablets, the hyperpigmentation of the patient 's skin was gradually reduced, and the symptoms of blurred vision were not significantly improved. We also reviewed the available literature on HCQ-induced cutaneous hyperpigmentation and bull's-eye macular lesions and described the clinical features of HCQ-induced cutaneous hyperpigmentation and bull's-eye macular lesions. In conclusion, clinicians should be aware of early cutaneous symptoms and HCQ-associated ophthalmotoxicity in patients with rheumatic diseases on HCQ sulphate and should actively monitor patients, have them undergo regular ophthalmological examinations and give appropriate treatment to prevent exacerbation of symptoms.

Bioinspired Flexible Hydrogelation with Programmable Properties for Tactile Sensing.

Tactile sensing requires integrated detection platforms with distributed and highly sensitive haptic sensing capabilities along with biocompatibility, aiming to replicate the physiological functions of the human skin and empower industrial robotic and prosthetic wearers to detect tactile information. In this regard, short peptide-based self-assembled hydrogels show promising potential to act as bioinspired supramolecular substrates for developing tactile sensors showing biocompatibility and biodegradability. However, the intrinsic difficulty to modulate the mechanical properties severely restricts their extensive employment. Herein, by controlling the self-assembly of 9-fluorenylmethoxycarbonyl-modifid diphenylalanine (Fmoc-FF) through introduction of polyethylene glycol diacrylate (PEGDA), wider nanoribbons are achieved by untwisting from well-established thinner nanofibers, and the mechanical properties of the supramolecular hydrogels can be enhanced 10-fold, supplying bioinspired supramolecular encapsulating substrate for tactile sensing. Furthermore, by doping with poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) and 9-fluorenylmethoxycarbonyl-modifid 3,4-dihydroxy-l-phenylalanine (Fmoc-DOPA), the Fmoc-FF self-assembled hydrogels can be engineered to be conductive and adhesive, providing bioinspired sensing units and adhesive layer for tactile sensing applications. Therefore, the integration of these modules results in peptide hydrogelation-based tactile sensors, showing high sensitivity and sustainable responses with intrinsic biocompatibility and biodegradability. The findings establish the feasibility of developing programmable peptide self-assembly with adjustable features for tactile sensing applications.

CD4+ CAR-T cell exhaustion associated with early relapse of multiple myeloma after BCMA CAR-T cell therapy.

Multiple myeloma is characterized by frequent clinical relapses following conventional therapy. Recently, chimeric antigen receptor T (CAR-T) cells targeting B-cell maturation antigen (BCMA) has been established as a treatment option for patients with relapsed or refractory disease. However, while >70% of patients initially respond to this treatment, clinical relapse and disease progression occur in most cases. Recent studies showed persistent expression of BCMA at the time of relapse, indicating that immune intrinsic mechanisms may contribute to this resistance. While there were no pre-existing T cell features associated with clinical outcomes, we found that patients with a durable response to CAR-T cell treatment had greater persistence of their CAR-T cells compared to patients with transient clinical responses. They also possessed a significantly higher proportion of CD8+ T effector memory cells. In contrast, patients with short-lived responses to treatment have increased frequencies of cytotoxic CD4+ CAR-T cells. These cells expand in vivo early after infusion but express exhaustion markers (HAVCR2 and TIGIT) and remain polyclonal. Finally, we demonstrate that non-classical monocytes are enriched in the myeloma niche and may induce CAR-T cell dysfunction through mechanisms that include TGFß. These findings shed new light on the role of cytotoxic CD4+ T cells in disease progression after CAR-T cell therapy.

Prevalence, characteristics, evaluation, and management of carotid body tumors: Systematic analysis based on available evidence.

OBJECTIVE: Although carotid body tumors (CBTs) are rare, they attract particular attention because of their propensity for malignant transformation and the high surgical risk. Because data are scarce and as it is difficult to achieve a large sample size, no study has yet comprehensively analyzed the characteristics, management, or operative complications of CBTs. Therefore, we collected and analyzed all currently available information on CBTs and used the pooled data to derive quantitative information on disease characteristics and management. METHODS: We systematically searched PubMed, Embase, the Cochrane Library, and the Web of Science up to December 1, 2022, for studies that investigated the characteristics and management of CBTs. The primary objective was to identify the prevalence of the various characteristics and the incidence of complications. The secondary objective was to compare patients who underwent preoperative embolization (PE) and those who did not (non-PE), as well as to compare patients with different Shamblin grades and those with and without succinate dehydrogenase (SDH) mutations in terms of CBT characteristics and complications. Two reviewers selected studies for inclusion and independently extracted data. All statistical analyses were performed using the standard statistical procedures of Review Manager 5.2 and Stata 12.0. RESULTS: A total of 155 studies with 9291 patients and 9862 tumors were identified. The pooled results indicated that the median age of patients with CBT was 45.72 years, and 65% were female. The proportion of patients with bilateral lesions was 13%. In addition, 16% of patients had relevant family histories, and the proportion of those with SDH gene mutations was 36%. Sixteen percent of patients experienced multiple paragangliomas, and 12% of CBTs had catecholamine function. The incidence of cranial nerve injury (CNI) was 27%, and 14% of patients suffered from permanent CNI. The incidence rates of operative mortality and stroke were both 1%, and 4% of patients developed transient ischemic attacks. Of all CBTs, 6% were malignant or associated with metastases or recurrences. The most common metastatic locations were the lymph nodes (3%) and bone (3%), followed by the lungs (2%). Compared with non-PE, PE reduced the estimated blood loss (standardized mean difference, -0.95; 95% confidence interval [CI], -1.70 to -0.20) and the operation time (standardized mean difference, -0.56; 95% CI, -1.03 to -0.09), but it increased the incidence of stroke (odds ratio, 2.44; 95% CI, 1.04-5.73). Higher Shamblin grade tumors were associated with more operative complications. Patients who were SDH gene mutation-positive were more likely to have a relevant family history and had more symptoms. CONCLUSIONS: CBT was most common in middle-aged females, and early surgical resection was feasible; there was a low incidence of serious operative complications. Routine PE is not recommended because this may increase the incidence of stroke, although PE somewhat reduced the estimated blood loss and operation time. Higher Shamblin grade tumors increased the incidence of operative complications. Patients who were SDH gene mutation-positive had the most relevant family histories and symptoms.

A new mouse-fixation device for IOP measurement in awake mice.

Glaucoma is an irreversible blinding eye disease. The mechanisms underlying glaucoma are complex. Up to now, no successful remedy has been found to completely cure the condition. High intraocular pressure (IOP) is an established risk factor for glaucoma and the only known modifiable factor for glaucoma treatment. Mice have been widely used to study glaucoma pathogenesis. IOP measurement is an important tool for monitoring the potential development of glaucomatous phenotypes in glaucoma mouse models. Currently, there are two methods of IOP measurement in mice: invasive and non-invasive. As the invasive method can cause corneal damage and inflammation, and most of the noninvasive method involves the use of anesthetics. In the course of our research, we designed a mouse fixation device to facilitate non-invasive measurements of mouse IOPs. Using this device, mouse IOPs can be accurately measured in awake mice. This device will help researchers to accurately assess mouse IOP without the use of anesthetics.

Prevalence and risk factors of thyroid nodules in breast cancer women with different clinicopathological characteristics: a cross-sectional study.

BACKGROUND: Association between breast cancer (BC) and thyroid nodules (TNs) is still unclear. This research was to estimate the prevalence and risk factors of TN in Chinese BC women at initial diagnosis. METHODS: 1731 Chinese early-stage BC women at initial diagnosis underwent thyroid ultrasound and 1:1 age-matched Chinese healthy women underwent health examination in corresponding period were enrolled for analysis. RESULTS: Prevalence of TN and TI-RADS ≥ 4 TN in BC patients (56.27% and 9.76%) were higher than healthy people (46.04% and 5.49%), respectively, P < 0.001. Among BC patients, prevalence of TN and TI-RADS ≥ 4 TN in hormone receptor (HR)-positive patients (59.57% and 11.81%) were higher than HR-negative patients (48.77% and 5.10%), respectively, P < 0.001, while without difference between HR-negative patients and healthy people. After adjusting for age and BMI, HR-positive patients had higher risk of TN (OR = 1.546, 95%CI 1.251-1.910, P < 0.001) and TI-RADS ≥ 4 TN (OR = 3.024, 95%CI 1.943-4.708, P < 0.001) than HR-negative patients. Furthermore, the risk of TI-RADS ≥ 4 TN was higher in patients with estrogen receptor (ER) positive (OR = 2.933, 95%CI 1.902-4.524), progesterone receptor (PR) positive (OR = 1.973, 95%CI 1.378-2.826), Ki-67 < 20% (OR = 1.797, 95%CI 1.280-2.522), and tumor size < 2 cm (OR = 1.804, 95%CI 1.276-2.552), respectively, P < 0.001. CONCLUSIONS: Prevalence of TN, especially TI-RADS ≥ 4 TN, in Chinese early-stage BC women was higher than healthy people. HR-positive patients had higher prevalence and risk of TN, while without difference between HR-negative patients and healthy people. The increased risk of TN was correlated with ER-positive, PR-positive, lower Ki-67 expression, and smaller tumor size.

Novel Pt(IV) complexes containing salvigenin ligand reverse cisplatin-induced resistance by inhibiting Rap1b-mediated cancer cell stemness in esophageal squamous cell carcinoma treatments.

Esophageal squamous cell carcinoma (ESCC) is a malignant tumor that is highly susceptible to metastasis, recurrence and resistance, and few therapeutic targets have been identified and proven effective. Herein, we demonstrated for the first time that Rap1b can positively regulate ESCC cell stemness, as well as designed and synthesized a novel class of Pt(IV) complexes that can effectively inhibit Raplb. In vitro biological studies showed that complex-1 exhibited stronger cytotoxicity than cisplatin and oxaliplatin against a variety of ESCC cells, and effectively reversed cisplatin-induced resistance of TE6 cells by increasing cellular accumulation of platinum and inhibiting cancer cell stemness. Significantly, complex-1 also exhibited strong ability to reversal cisplatin-induced cancer cell resistance and inhibit tumor growth in TE6/cDDP xenograft mice models, with a tumor growth inhibition rate of 73.3 % at 13 mg/kg and did not show significant systemic toxicity. Overall, Rap1b is a promising target to be developed as an effective treatment for ESCC. Complex-1, as the first Pt(IV) complex that can strongly inhibit Rap1b, is also worthy of further in-depth study.