SIRT7 remodels the cytoskeleton via RAC1 to enhance host resistance to Mycobacterium tuberculosis.

Phagocytosis of Mycobacterium tuberculosis (Mtb) followed by its integration into the matured lysosome is critical in the host defense against tuberculosis. How Mtb escapes this immune attack remains elusive. In this study, we unveiled a novel regulatory mechanism by which SIRT7 regulates cytoskeletal remodeling by modulating RAC1 activation. We discovered that SIRT7 expression was significantly reduced in CD14+ monocytes of TB patients. Mtb infection diminished SIRT7 expression by macrophages at both the mRNA and protein levels. SIRT7 deficiency impaired actin cytoskeleton-dependent macrophage phagocytosis, LC3II expression, and bactericidal activity. In a murine tuberculosis model, SIRT7 deficiency detrimentally impacted host resistance to Mtb, while Sirt7 overexpression significantly increased the host defense against Mtb, as determined by bacterial burden and inflammatory-histopathological damage in the lung. Mechanistically, we demonstrated that SIRT7 limits Mtb infection by directly interacting with and activating RAC1, through which cytoskeletal remodeling is modulated. Therefore, we concluded that SIRT7, in its role regulating cytoskeletal remodeling through RAC1, is critical for host responses during Mtb infection and proposes a potential target for tuberculosis treatment.IMPORTANCETuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a significant global health issue. Critical to macrophages' defense against Mtb is phagocytosis, governed by the actin cytoskeleton. Previous research has revealed that Mtb manipulates and disrupts the host's actin network, though the specific mechanisms have been elusive. Our study identifies a pivotal role for SIRT7 in this context: Mtb infection leads to reduced SIRT7 expression, which, in turn, diminishes RAC1 activation and consequently impairs actin-dependent phagocytosis. The significance of our research is that SIRT7 directly engages with and activates Rac Family Small GTPase 1 (RAC1), thus promoting effective phagocytosis and the elimination of Mtb. This insight into the dynamic between host and pathogen in TB not only broadens our understanding but also opens new avenues for therapeutic development.

Mitochondrial targeted modification and anticancer mechanism of natural product ergosterol peroxide.

Ergosterol peroxide (EP) isolated from the edible medicinal fungus Pleurotus ferulae has a wide range of anti-tumor activity, but poor water solubility and low bioavailability limit further application. In this study, EP was structurally modified using triphenylphosphine (TPP+), which combines mitochondrial targeting, amphiphilicity, and cytotoxicity. A series of TPP+-conjugated ergosterol peroxide derivatives (TEn) with different length linker arms were synthesized. The structure-activity relationship showed that the anticancer activity of TEn gradually decreased with the elongation of the linker arm. The compound TE3 has the optimal and broadest spectrum of antitumor effects. It mainly through targeting mitochondria, inducing ROS production, disrupting mitochondrial function, and activating mitochondria apoptosis pathway to exert anti-cervical cancer activity. Among them, TPP+ only acted as a mitochondrial targeting group, while EP containing peroxide bridge structure served as an active group to induce ROS. In vivo experiments have shown that TE3 has better anti-cervical cancer activity and safety than the first-line anticancer drug cisplatin, and can activate the immune response in mice. Although TE3 exhibits some acute toxicity, it is not significant at therapeutic doses. Therefore, TE3 has the potential for further development as an anti-cervical cancer drug.

Myriocin enhances the clearance of M. tuberculosis by macrophages through the activation of PLIN2.

Myriocin is an inhibitor of de novo synthesis of sphingolipids and ceramides. In this research, we showed myriocin could significantly reduce Mtb burden and histopathological inflammation in mice. However, the underlying mechanism remains unclear. RNA-seq analysis revealed a significant increase in gene expression of PLIN2/CD36/CERT1 after myriocin treatment. The reduced bactericidal burden was only reversed after silencing the lipid droplets (LDs) surface protein PLIN2. This suggests that myriocin enhances the ability of macrophages to clear Mtb depending on the PLIN2 gene, which is part of the PPARγ pathway. Indeed, we observed a significant increase in the number of LDs following myriocin treatment.IMPORTANCEMycobacterium tuberculosis has the ability to reprogram host cell lipid metabolism and alter the antimicrobial functions of infected macrophages. The sphingolipids, such as ceramides, are the primary host lipids utilized by the bacteria, making the sphingomyelinase/ceramide system critical in Mtb infections. Surprisingly, the antimicrobial effect of myriocin was found to be independent of its role in reducing ceramides, but instead, it depends on the lipid droplets surface protein PLIN2. Our findings provide a novel mechanism for how myriocin enhances Mtb clearance in macrophages.

Progesterone receptor impairs immune respond and down-regulates sensitivity to anti-LAG3 in breast cancer.

BACKGROUND: Progesterone receptor (PR) serves as a crucial prognostic and predictive marker in breast cancer. Nonetheless, the interplay between PR and the tumor immune microenvironment remains inadequately understood. This investigation employs bioinformatics analyses, mouse models, and clinical specimens to elucidate the impact of PR on immune microenvironment and identify potential targets for immunotherapy, furnishing valuable guidance for clinical practice. METHODS: Analysis of immune infiltration score by Xcell between PR-positive and PR-negative breast cancer tumors. Construction of overexpression mouse progesterone receptor (mPgr) EMT-6 cell was to explore the tumor immune microenvironment. Furthermore, anti- Lymphocyte-activation gene 3 (LAG3) therapy aimed to investigate whether PR could influence the effectiveness of immune treatments. RESULTS: Overexpression mPgr inhibited tumor growth in vitro, but promoted tumor growth in Balb/c mouse. Flow cytometry showed that the proportion and cytotoxicity of CD8+T cells in tumor of overexpressing mPgr group were significantly reduced. The significant reduction in overexpressing mPgr group was found in the proportions of LAG3+CD8+ T cells and LAG3+ Treg T cells. Anti-LAG3 treatment resulted in reduced tumor growth in EV group mouse rather than in overexpressing mPgr group. Patents derived tumor fragment (PDTF) also showed higher anti-tumor ability of CD3+T cell in patents' tumor with PR <20% after anti-human LAG3 treatment in vitro. CONCLUSIONS: The mPgr promotes tumor growth by downregulating the infiltration and function of cytotoxic cell. LAG3 may be a target of ER-positive breast cancer immunotherapy. The high expression of PR hinders the sensitivity to anti-LAG3 treatment.

1T-2H Mixed-Phase MoS2 Stabilized with a Hyperbranched Polyethylene Ionomer for Mg2+ /Li+ Co-Intercalation Toward High-Capacity Dual-Salt Batteries.

Dual-salt magnesium/lithium-ion batteries (MLIBs) benefit from fast lithium ion diffusion on the cathode side while providing safety due to the dendrite-free Mg2+ stripping/plating mechanism on the anode side. Bulk MoS2 (B-MoS2 ), as a cathode for magnesium-ion batteries (MIBs), suffers from low conductivity and relatively van der Waals gaps and, consequently, resists against divalent Mg2+ insertion due to the high Coulombic interactions. In MLIBs, it exhibits a Daniell-cell type mechanism with the sole accommodation of Li+ . In this paper, the synthesis of a 1T/2H mixed-phase MoS2 (MP-MoS2 ) modified with a hyperbranched polyethylene ionomer, I@MP-MoS2 , for high-capacity MLIBs with a distinct Mg2+ /Li+ co-intercalation mechanism is reported. Benefiting from the enhanced conductivity (due to 53% metallic 1T phase), expanded van der Waals gaps (79% expansion compared to B-MoS2 , 1.11 vs 0.62 nm), and enhanced interactions with THF-based electrolytes following the modification, I@MP-MoS2 shows a dramatically increased Mg2+ storage compared to its parent analogue (144 mAh g-1 vs ≈2 mAh g-1 at 20 mA g-1 ). In MLIBs, I@MP-MoS2 is demonstrated to exhibit remarkable specific capacities up to ≈270 mAh g-1 at 20 mA g-1 through a Mg2+ /Li+ co-intercalation mechanism with 87% of capacity retention over 200 cycles at 100 mA g-1 .

Effect of collateral circulation in patients with multiple craniocervical artery stenoses.

Based on previous findings, collateral circulation in the brain is vital in mitigating cerebral ischemia's effects and influencing stroke risk. This retrospective study examined collateral circulation, admission ischemic stroke status, and long-term recurrence in patients with multiple craniocervical artery stenoses. Consecutive symptomatic internal carotid artery (ICA) stenosis patients from the First Affiliated Hospital of Soochow University were recruited. Baseline data including medical histories and neurological function at admission were collected. Imaging techniques assessed collateral compensative capacity. Multivariate logistic regression analysis was used to investigate the association between collateral circulation and case status. A total of 559 patients with symptomatic ICA stenosis were included, among whom 153 (27.4%) had concurrent moderate to severe vertebro-basilar artery (VBA) stenosis. Dizziness, weakness/numbness, and slurring of speech were the primary symptoms in all patients. Over 36 months, 71 (12.7%) patients experienced a recurrence of acute ischemic stroke (AIS). In multivariate analysis, collateral circulation was found to be negatively associated with AIS (regional leptomeningeal collateral [rLMC] scores: OR: 0.798, 95% CI: 0.743-0.857, p < 0.001; Tan scores: OR: 0.478, 95% CI: 0.336-0.679, p < 0.001). Meanwhile, the collateral circulation scores were significantly associated with the recurrence of AIS within 3 years (rLMC scores: OR: 0.926, 95% CI: 0.860-0.997, p = 0.042; Tan scores: OR: 0.467, 95% CI: 0.306-0.712, p < 0.001). Most associations remained significant in the subgroup of patients with VBA stenosis. Favorable collateral circulation in multiple craniocervical artery stenosis patients reduced long-term ischemic event recurrence. Stratifying treatment risks is essential for optimizing outcomes.

Clinical analysis and methodological evaluation of syphilis infection in patients in a first-class tertiary hospital in Suzhou, China.

OBJECTIVE: To explore the distribution and epidemiological characteristics of patients with syphilis in a first-class tertiary hospital and to evaluate the coincidence rate between chemiluminescence immunoassay (CLIA) and Treponema pallidum particle agglutination assay (TPPA). METHODS: The medical records of 247,501 outpatients and inpatients were retrospectively analyzed. TPPA was used to verify positive and suspected cases, and the coincidence rate between CLIA and TPPA was evaluated. Receiver operating characteristic (ROC) curve was used to determine optimal diagnostic thresholds. RESULTS: Of the 247,501 serum samples, 5,173 were detected positive for syphilis using CLIA, with a detection rate of 2.09% and a men-to-women ratio of 1.39. The chi-square test showed that sex and age were both factors that affected the detection rate (χ2=229.51, P < 0.0001). In addition, urology, orthopedics, cardiology, general surgery, gastroenterology, and gynecology represented the top six departments with the highest numbers of positive cases. Comparative analysis showed that the overall coincidence rate between CLIA and TPPA was 80.24%. Analysis of the ROC curve showed that the area under the curve (AUC) was 0.936 (95% confidence interval [CI]: 0.929-0.942, P < 0.0001) using sample/cut-off value (S/CO) as a diagnostic indicator. The results showed that an S/CO value of 3.945 was the best diagnostic value for the CLIA method, with a diagnostic specificity of 93.64% and a sensitivity of 81.90%. CONCLUSIONS: Syphilis is widely distributed in various hospital departments and primarily affects middle-aged and older individuals. For cases that have been initially screened as positive or suspicious, TPPA and other tests should be used for verification to avoid misdiagnosis and missed diagnosis.

The impact of global warming on the signature virulence gene, thermolabile hemolysin, of Vibrio parahaemolyticus.

IMPORTANCE: In this study, Vibrio parahaemolyticus strains were collected from a large number of aquatic products globally and found that temperature has an impact on the virulence of these bacteria. As global temperatures rise, mutations in a gene marker called thermolabile hemolysin (tlh) also increase. This suggests that environmental isolates adapt to the warming environment and become more pathogenic. The findings can help in developing tools to analyze and monitor these bacteria as well as assess any link between climate change and vibrio-associated diseases, which could be used for forecasting outbreaks associated with them.

Construction and validation of nomograms to reduce completion thyroidectomy by predicting lymph node metastasis in low-risk papillary thyroid carcinoma.

CONTEXT: More than 5 central lymph nodes metastases (CLNM) or lateral lymph node metastasis (LLNM) indicates a higher risk of recurrence in low-risk papillary thyroid carcinoma (PTC) and may lead to completion thyroidectomy (CTx) in patients initially undergoing lobectomy. OBJECTIVE: To screen potentially high-risk patients from low-risk patients by using preoperative and intraoperative clinicopathological features to predict lymph node status. METHODS: A retrospective analysis of 8301 PTC patients in Wuhan Union Hospital database (2009-2021) was performed according to the 2015 American Thyroid Association (ATA) and 2021 National Comprehensive Cancer Network (NCCN) guidelines, respectively. Logistic regression and best subsets regression were used to identify risk factors. Nomograms were established and externally validated using the Differentiated Thyroid Cancer in China cohort. RESULTS: More than 5 CLNM or LLNM was detected in 1648 (19.9%) patients. Two predictive models containing age, gender, maximum tumor size, free thyroxine (FT4) and palpable node (all p < 0.05) were established. The nomogram based on NCCN criteria showed better discriminative power and consistency with a specificity of 0.706 and a sensitivity of 0.725, and external validation indicated that 76% of potentially high-risk patients could achieve preoperative conversion of surgical strategy. CONCLUSIONS: Models based on large cohorts with good predictive performance were constructed and validated. Preoperative low-risk (T1-2N0M0) patients with age younger than 40 years, male gender, large tumor size, low FT4 and palpable nodes may be at high risk of LLNM or more than 5 CLNM, and they should receive more aggressive initial therapy to reduce CTx.

Mycobacterium tuberculosis-Induced Prostaglandin J2 and 15-Deoxy-Prostaglandin J2 Inhibit Inflammatory Signals in Human M1 Macrophages via a Negative Feedback Loop.

Tuberculosis caused by Mycobacterium tuberculosis is a leading cause of death globally and a major health concern. In humans, macrophages are the first line invaded by M. tuberculosis. Upon infection, macrophages upregulate cyclooxygenase-2 (COX-2) expression and consequently elevate the formation of PGs, including PGE2 and PGD2. Although the role of proinflammatory PGE2 in M. tuberculosis infection has been reported, the roles of PGJ2 and 15-deoxy-PGJ2 (collectively named J2-PGs), the metabolites of PGD2 with anti-inflammatory features, remain elusive. In this study, we show that M. tuberculosis (H37Rv strain)-conditioned medium stimulates human monocyte-derived macrophages (MDMs) to elevate COX-2 expression along with robust generation of PGJ2, exceeding PGD2 formation, and to a minor extent also of 15-deoxy-PGJ2. Of interest, in M1-MDM phenotypes, PGJ2 and 15-deoxy-PGJ2 decreased M. tuberculosis (H37Rv strain)-conditioned medium-induced COX-2 expression and related PG formation by a negative feedback loop. Moreover, these J2-PGs downregulated the expression of the proinflammatory cytokines IL-6, IL-1ß, and IFN-γ, but elevated the anti-inflammatory cytokine IL-10 and the M2 markers arginase-1 and CD163. These anti-inflammatory effects of J2-PGs in M1-MDM correlated with impaired activation of TGF-ß-activated kinase 1/NF-κB/MAPK pathways. Finally, we found that J2-PGs regulate COX-2 expression, at least partially, via PGD2 receptor (DP1) and chemoattractant receptor homologue expressed on Th2 cells/DP2 receptors, but independent of the J2-PG receptor peroxisome proliferator-activated receptor-γ. Together, our findings reveal that M. tuberculosis induces COX-2 expression in human M1-MDMs, along with robust formation of J2-PGs that mediates anti-inflammatory effects via a negative feedback loop.

Association of concomitant headache with hypoperfusion in ischemic stroke: A multimodal CT-based study.

Previous investigations indicate that vessel wall elasticity may contribute to the occurrence of an ischemic stroke-associated headache. In this prospective study, the association between radiologic parameters of intracranial hemodynamic changes and concomitant headaches during the early phase of ischemic stroke was examined. Consecutive patients with acute ischemic stroke (AIS) from the First Affiliated Hospital of Soochow University were recruited and divided into two groups according to their questionnaire results and the International Classification of Headache Disorder 3 criteria. Baseline data, including stroke sub-types and neurological function, at admission and discharge were collected. Non-contrast computed tomography (CT), CT angiography, and CT perfusion were performed to assess intracranial hemodynamic changes. Multiple adjusted logistic models were used and possible confounding factors were included in sequential models. A total of 190 patients with AIS (93 headaches and 97 non-headache) were recruited. There were significant differences between the two groups in gender, hypertension, Alberta stroke program early CT score, relative cerebral blood flow (rCBF), and relative cerebral blood volume (rCBV). Furthermore, rCBV (adjusted odds ratio [OR] 0.160; 95% confidence interval [CI], 0.055-0.461; p < 0.001) and rCBF (adjusted OR, 0.309; 95% CI, 0.113-0.844; p < 0.05) were significantly associated with concomitant headache during the early phase of AIS in fully adjusted models. After adjusting for sociodemographic characteristics and other confounding factors, p values for the ORs were robust and intensified. Patients with lower rCBV and rCBF tended to experience the concomitant headache during the early phase of AIS. Regional hypoperfusion and microcirculation might play an important role in this separate clinical entity.

Mycobacterium tuberculosis Utilizes Host Histamine Receptor H1 to Modulate Reactive Oxygen Species Production and Phagosome Maturation via the p38MAPK-NOX2 Axis.

Tuberculosis (TB), which is caused by the single pathogenic bacterium, Mycobacterium tuberculosis, is among the top 10 lethal diseases worldwide. This situation has been exacerbated by the increasing number of cases of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). Histamine is an organic nitrogenous compound that mediates a plethora of cell processes via different receptors. The expression of histamine receptor H1 (HRH1), one of the four histamine receptors identified to date was previously reported to be augmented by M. tuberculosis infection, although the underlying mechanism is unclear. In the present study, we applied confocal microscopy, flow cytometry, and Western blotting to show that HRH1 expression was enhanced in macrophages following mycobacterial infection. Furthermore, by combining techniques of gene knockdown, immunoprecipitation, intracellular bacterial burden analysis, fluorescence labeling, and imaging, we found that M. tuberculosis targeted the host HRH1 to suppress NOX2-mediated cROS production and inhibit phagosome maturation and acidification via the GRK2-p38MAPK signaling pathway. Our findings clarified the underlying mechanism of the M. tuberculosis and host HRH1 interaction and may provide useful information for the development of novel antituberculosis treatments. IMPORTANCE Once engulfed in macrophage phagosomes, M. tuberculosis adopts various strategies to take advantage of the host environment for its intracellular survival. Histamine is an organic nitrogen-containing compound that mediates a plethora of cellular processes via different receptors, but the crosstalk mechanism between M. tuberculosis and HRH1 in macrophages is not clear. Our results revealed that M. tuberculosis infection enhanced HRH1 expression, which in turn restrained macrophage bactericidal activity by modulating the GRK2-p38MAPK signaling pathway, inhibiting NOX2-mediated cROS production and phagosome maturation. Clarification of the underlying mechanism by which M. tuberculosis utilizes host HRH1 to favor its intracellular survival may provide useful information for the development of novel antituberculosis treatments.

Real-time intraoperative near-infrared autofluorescence imaging to locate the parathyroid glands: A preliminary report.

Identification and localization of parathyroid glands (PGs) remains a challenge for surgeons. The aim of this study was to evaluate the efficiency of intraoperative near-infrared autofluorescence (NIRAF) imaging to detect PGs in thyroid and parathyroid diseases. Seventy-six patients undergoing surgery for thyroid or parathyroid diseases between July 9, 2020 and August 20, 2021 were retrospectively analyzed. Intraoperative carbon nanoparticle (CN) negative imaging and handheld NIRAF imaging were successively performed for each patient. Of 206 PGs that needed to be identified for surgery, 162 were identified by NIRAF imaging, with a theoretical rate of identification of 78.64%. This was higher than the rate of identification with CN negative imaging, which was 75.73%. The number of PGs identified by NIRAF imaging and CN negative imaging did not differ significantly in either total thyroidectomy or thyroid lobectomy. In addition, the autofluorescence (AF) intensity of secondary parathyroid adenoma was weaker than that of normal PGs. NIRAF imaging is potentially a more efficient tool for identification of PGs than CN negative imaging, with a shorter learning curve and lower risk. It may not be well-suited to secondary hyperthyroidism or adenoma, but it was more efficient at identifying excised specimens than visual identification by a surgeon.

Case Report: Implantation of Dedifferentiated to Poorly Differentiated Thyroid Carcinoma After Endoscopic Thyroid Surgery.

Background: Endoscopic thyroidectomy is widely accepted for its advantages. However, implant metastasis remains a significant complication of endoscopic thyroidectomy. Methods: This is the first report of breast implantation diagnosed with poorly differentiated thyroid carcinoma following endoscopic thyroidectomy. Results: We present a case of a 35-year-old woman who was initially diagnosed with a 3.0 cm conventional papillary thyroid carcinoma after endoscopic thyroidectomy via total areola. Two years later, she was reported to have recurring poorly differentiated thyroid carcinoma in the right areola. Implantation after endoscopic thyroidectomy is rare, and even rarer is dedifferentiated papillary thyroid carcinoma around the implant site. Conclusions: Stringently evaluated endoscopic surgery indications, appropriate preoperative evaluation, meticulous surgical technique, and adequate protective measures can significantly reduce the incidence of local implantation or recurrence.

Proteomics in Biomarker Discovery for Tuberculosis: Current Status and Future Perspectives.

Tuberculosis (TB) continues to threaten many peoples' health worldwide, regardless of their country of residence or age. The current diagnosis of TB still uses mainly traditional, time-consuming, and/or culture-based techniques. Efforts have focused on discovering new biomarkers with higher efficiency and accuracy for TB diagnosis. Proteomics-the systematic study of protein diversity-is being applied to the discovery of novel protein biomarkers for different types of diseases. Mass spectrometry (MS) technology plays a revolutionary role in proteomics, and its applicability benefits from the development of other technologies, such as matrix-based and immune-based methods. MS and derivative strategies continuously contribute to disease-related discoveries, and some promising proteomic biomarkers for efficient TB diagnosis have been identified, but challenges still exist. For example, there are discrepancies in the biomarkers identified among different reports and the diagnostic accuracy of clinically applied proteomic biomarkers. The present review summarizes the current status and future perspectives of proteomics in the field of TB biomarker discovery and aims to elicit more promising findings for rapid and accurate TB diagnosis.

Interleukin-18 mediated inflammatory brain injury after intracerebral hemorrhage in male mice.

Interleukin-18 (IL-18), a pro-inflammatory cytokine, is thought to be associated with inflammation in many neurological diseases such as ischemic stroke and poststroke depression, but the role of IL-18 in inflammatory injury after intracerebral hemorrhage (ICH) remains unclear. In this study, we established the ICH model in male mice and found that IL-18 expression including protein and mRNA levels was significantly increased in brain tissues after ICH. Meanwhile, exogenous IL-18 exacerbated cerebral hematoma and neurological deficits following ICH. In the IL-18 knockout group, the size of hematoma and neurological functions after ICH was decreased compared with the wild-type group, suggesting the critical role of IL-18 on the modulation of brain injury after ICH. Importantly, exogenous IL-18 increased microglial activation in brain tissues after ICH. Furthermore, IL-18 knockout resulted in the reduction of activated microglia after ICH. These results indicated that IL-18 may regulate the inflammatory response after ICH through the activation of microglia. Thus, IL-18 is expected to be a promising therapeutic target for secondary brain injury after ICH.

Influence of progesterone receptor on metastasis and prognosis in breast cancer patients with negative HER-2.

BACKGROUND: In de novo metastatic breast cancer patients, the site of metastasis and prognosis are related to the molecular subtype of breast cancer. There are few relevant reports to explore the clinicopathological and prognostic characteristics of different single positive hormone receptor subtypes [estrogen receptor (ER)+/progesterone receptor (PR)- and ER-/PR+] of metastatic breast cancer. METHODS: Using the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2015.We analyzed the metastatic patterns and prognosis of human epidermal growth factor receptor 2 (HER-2)-negative breast cancer patients. Cox analysis was used to analyze the influence of ER+/PR- and ER-/PR+ on the prognosis of patients in different subgroups and the risk factors affecting the prognosis of patients with single hormone receptor positivity. RESULTS: We included 206,187 breast cancer patients, including 7,726 stage IV patients. The loss of ER was a protective factor against bone metastasis (P<0.001) and a risk factor for visceral metastasis (P<0.001). The ER-/PR+ subtype had a similar proportion of de novo metastatic breast cancer, and similar clinicopathological characteristics, prognosis with triple negative breast cancer (TNBC). Single PR positivity was an independent risk factor for cancer specific survival (CSS) in multi-visceral metastasis subgroup comparing to TNBC. Meanwhile, no significant difference in overall survival (OS) or breast cancer specific survival (BCSS) between ER-/PR+ and ER-/PR- patients in all breast cancer patients or in stage IV breast cancer patients. Age [hazard ratio (HR) =2.16], grade (HR =2.36), T stage (T4: HR =3.24), lymph node metastasis (>10: HR =4.33), distant metastasis (HR =4.99), and no chemotherapy or an unknown (HR =1.65) were high-risk factors but surgery (HR <0.5) were protective factors for CSS in ER-/PR+ patients. CONCLUSIONS: ER-/PR+ subtype had a high proportion of stage IV patients. Meanwhile, such subtype breast cancer had similar clinicopathological characteristics, metastatic models (prefers to visceral metastasis), similar even worse prognosis compared with TNBC.

Cleanup of oiled shorelines using a dual responsive nanoclay/sodium alginate surface washing agent.

Oil spills may affect ecosystems and endanger public health. In this study, we developed a novel and dual responsive nanoclay/sodium alginate (NS) washing fluid, and systematically evaluated its application potential in oiled shoreline cleanup. The characterization results demonstrated that sodium alginate combined with nanoclay via hydrogen bonds, and was inserted into the interlayer spacing of nanoclay. Adding sodium alginate reduced surface and interfacial tensions, while increasing the viscoelasticity of the washing fluid. Batch experiments were conducted to investigate oil removal performance under various conditions. Additionally, the factorial design analysis showed that three single factors (temperature, oil concentration, and salinity), and two interactive effects (temperature/salinity; and oil concentration/HA) displayed significant effects on the oil removal efficiency of the NS washing fluid. Compared to the commercial surfactants, the NS composite exhibited satisfactory removal efficiencies for treating oily sand. Green materials-stabilized Pickering emulsion can potentially be used for oil/water separation. The NS washing agent displayed excellent pH- and Ca2+- responsiveness, generating transparent supernatants with low oil concentration and turbidity. Our work opens an interesting avenue for designing economical, high performance, and green washing agents.

Presentation and survival by hormonal receptor status in metaplastic breast cancer: A propensity score-matched analysis.

BACKGROUND: Metaplastic breast cancer (MBC) is a rare and aggressive form of breast cancer. The effectiveness of chemotherapy (CT) for MBC remains controversial. The present study aimed to evaluate the efficacy of CT combined hormone receptor (HR) status on MBC patients with high risk (T1-4N2-3M0 and T4N0-1M0) by propensity-score matching (PSM). METHODS: A retrospective study was performed to analyze MBC from the SEER database. Breast cancer-specific survival (BCSS) was analyzed using the Kaplan-Meier curve. Cox proportional hazard models were used to assess BCSS. PSM was used to make 1:1 case-control matching. RESULTS: This study identified 3116 patients. The median follow-up time was 44 months (range, 1-321 months). About 62.5 % of patients received CT. 23.0 % of patients were HR-positive. Recurrence risk had a significant difference between the HR-negative and HR-positive groups. In the multivariable Cox regression model, CT had no benefit for MBC patients. HR status was not associated with a better prognosis. In subgroup analysis, the Kaplan-Meier analysis showed that HR-negative MBC with intermediate-risk benefited from CT. For HR-positive MBC, patients with intermediate and high risk also benefited from CT. After PSM, neither CT nor HR status was not related to better BCSS. Moreover, the use of CT could only improve the survival of HR-positive MBC patients with high risk. CONCLUSION: PSM analysis showed that HR status was not associated with a better prognosis. CT was not a significant prognostic factor for prognosis. However, HR-positive MBC patients with high risk might benefit from CT.

High serum complement component C4 as a unique predictor of unfavorable outcomes in diabetic stroke.

Previous studies demonstrated that diabetic stroke patients had a poor prognosis and excess complement system activation in the peripheral blood. In this study, the association of serum complement levels with the prognosis of diabetic stroke was examined. Patients with acute ischemic stroke were recruited and were divided into two groups according to their history of diabetes. Baseline data on the admission, including C3 and C4 were collected. Neurologic function at discharge was the primary outcome and was quantified by the National Institutes of Health Stroke Scale (NIHSS). A total of 426 patients with acute ischemic stroke (116 diabetic strokes and 310 non-diabetic strokes) were recruited in this study. There were significant differences between the two groups in hypertension, coronary disease, triglyceride, high-density lipoprotein cholesterol, fasting blood sugar, C4, and mortality rates. Furthermore, the values of complement protein levels were divided into tertiles. In the diabetic stroke group, serum C4 level at the acute phase in the upper third was independently associated with NIHSS score at discharge and concurrent infection. These associations were not significant in non-diabetic stroke. High serum C4 level at admission, as a unique significant predictor, was associated with unfavorable clinical outcomes in the diabetic stroke, independently of traditional risk factors.