Lung abscess by Fusobacterium nucleatum and Streptococcus spp. co-infection by mNGS: A case series.

A lung abscess is a necrotizing infection caused by microbiomes that lead to the loss of healthy lung tissue. The routine culture is a waste of time and yields false-negative results, and clinicians could only choose empiric therapy or use broad-spectrum antibiotics, which could significantly contribute to the problem of resistance or aggravate the condition. We report three patients with a routine-culture-negative lung abscess. The presenting symptoms included fever, cough, dyspnea, and chest pain, and a computed tomography scan revealed a lesion in the lungs. The bronchoalveolar lavage fluid and pleural fluid were tested for pathogens using metagenome next-generation sequencing (mNGS), and the results revealed Fusobacterium nucleatum and Streptococcus spp. (S. constellatus, S. intermedius) as the most represented microbial pathogens. Our data demonstrated that mNGS could be a promising alternative diagnostic tool for pathogen detection, and the pathogen lists indicate that it will be important to focus on the Streptococcus genus rather than the dominant Streptococcus spp. in terms of co-infection of pathogen determined by shotgun mNGS.

Progress in Discography.

Discography is an important method for diagnosing discogenic low back pain (LBP) and replicating the effects of pain. However, its development is not smooth due to its safety and reliability, which have not been completely confirmed. Beginning with the clinicians using discography, there remains constant controversy. With the continuous progress of related research on discography, clinicians and scholars' understanding of discography is constantly improving. This article reviews the background, clinical application, and safety of discography.

SUMOylation of ERp44 enhances Ero1α ER retention contributing to the pathogenesis of obesity and insulin resistance.

OBJECTIVE: As the only E2 conjugating enzyme for the SUMO system, Ubc9-mediated SUMOylation has been recognized to regulate diverse biological processes, but its impact on adipocytes relevant to obesity and insulin resistance is yet to be elucidated. METHODS: We established adipocyte-specific Ubc9 deficient mice to explore the effects of Ubc9 on obesity and metabolic disorders induced by high-fat diet (HFD) in adult mice. The molecular targets of SUMOylation were explored by liquid chromatography-mass spectrometry, and the regulatory mechanism of SUMOylation in T2D was analyzed. RESULTS: Adipocyte-specific depletion of Ubc9 (AdipoQ-Cre-Ubc9fl/fl, Ubc9AKO) protected mice from HFD-induced obesity, insulin resistance, and hepatosteatosis. The Ubc9AKO mice were featured by the reduced HFD-induced endoplasmic reticulum (ER) stress and inflammatory response. Mechanically, over nutrition rendered adipocytes to undergo a SUMOylation turnover characterized by the change of SUMOylation levels and substrates. ERp44 displayed the highest change in terms of SUMOylation levels of substrates involved in ER-related functions. The lack of ERp44 SUMOylation at lysine 76 (K76) located within the thioredoxin (TRX)-like domain by Ubc9 deficiency enhanced its degradation and suppressed its covalent binding to Ero1α, an oxidase that exists in the ER but lacks ER retention motif, thereby alleviating endoplasmic reticulum stress by promoting Ero1α secretion. CONCLUSIONS: Our data suggest that modulation of ERp44 SUMOylation in adipocytes could be a feasible strategy against obesity and insulin resistance in clinical settings.

Development of Acridone Derivatives: Targeting c-MYC Transcription in Triple-Negative Breast Cancer with Inhibitory Potential.

Breast cancer, especially the aggressive triple-negative subtype, poses a serious health threat to women. Unfortunately, effective targets are lacking, leading to a grim prognosis. Research highlights the crucial role of c-MYC overexpression in this form of cancer. Current inhibitors targeting c-MYC focus on stabilizing its G-quadruplex (G4) structure in the promoter region. They can inhibit the expression of c-MYC, which is highly expressed in triple-negative breast cancer (TNBC), and then regulate the apoptosis of breast cancer cells induced by intracellular ROS. However, the clinical prospects for the application of such inhibitors are not promising. In this research, we designed and synthesized 29 acridone derivatives. These compounds were assessed for their impact on intracellular ROS levels and cell activity, followed by comprehensive QSAR analysis and molecular docking. Compound N8 stood out, significantly increasing ROS levels and demonstrating potent anti-tumor activity in the TNBC cell line, with excellent selectivity shown in the docking results. This study suggests that acridone derivatives could stabilize the c-MYC G4 structure. Among these compounds, the small molecule N8 shows promising effects and deserves further investigation.

Comprehensive Indicators for Evaluating and Seeking Elasto-Magnetic Parameters for High-Performance Cable Force Monitoring.

The elasto-magnetic method is a promising pathway for cable force monitoring in cable-stayed bridges. Under the action of an externally applied pulsed magnetic field, both the variation in the main flux recorded by the induction coil and the localized surface magnetic field measured by the packaged magnetic sensor are typical signals for observing the elasto-magnetic effect in tensioned cables. However, the performances of the parameters extracted from the two types of elasto-magnetic signals are never strictly compared in the experiment. Meanwhile, comprehensive indicators for evaluating the ability of elasto-magnetic parameters on cable force characterization are seldom discussed. As a result, it is difficult to compare the performances of elasto-magnetic devices developed by different teams, and the pathway of seeking new parameters for cable force monitoring is obstructed. In this study, elasto-magnetic calibration experiments were performed on a cable of seven-wire steel strands to simultaneously measure the variation in the main flux and the localized surface magnetic field. Comprehensive indicators considering sensitivity, hysteresis error, and cable force resolution are proposed to examine the performances of classic elasto-magnetic parameters and new candidate ones. Through comparative study, two new parameters demonstrated outstanding ability for cable force measurement, and they are the minimum amplitude of the induced voltage and the area under the curve between two points of 3 dB height of the voltage measured by a Hall sensor. The latter is recommended for high-performance cable force monitoring from the perspective of simplicity in sensor configuration.

Development and validation of a machine learning-based model for postoperative ischemic stroke in middle-aged and elderly patients with hip or knee arthroplasty.

Postoperative ischemic stroke in middle-aged and elderly patients with hip or knee arthroplasty remains a major postoperative challenge, little is known about its incidence and risk factors. This study sought to create a nomogram for precise prediction of ischemic stroke after hip or knee arthroplasty. Discharge data of all middle-aged and elderly patients undergoing primary hip or knee arthroplasty from May 2013 to October 2020 were queried. These patients were then followed up over time to determine their risk of ischemic stroke. Clinical parameters and blood biochemical features were analyzed by the use of univariable and multivariable generalized logistic regression analysis. A nomogram to predict the risk of ischemic stroke was constructed and validated with bootstrap resampling. Eight hundred twenty-eight patients were included for analysis; Fifty-one were diagnosed with ischemic stroke. After final regression analysis, age, the neutrophil-to-lymphocyte ratio (NLR), a standard deviation of red blood cell distribution width, American Society of Anesthesiologists, low-density lipoprotein, and diabetes were identified and were entered into the nomogram. The nomogram showed an area under the receiver operating characteristic curve of 0. 841 (95% confidence interval [CI], 0.809-0.871). The calibration curves for the probability of ischemic stroke showed optimal agreement between the probability as predicted by the nomogram and the actual probability (Hosmer-Lemeshow test: P = .818). We developed a practical nomogram that can predict the risk of ischemic stroke for middle-aged and elderly patients with hip or knee arthroplasty. This model has the potential to assist clinicians in making treatment recommendations.

Adipocyte-derived kynurenine promotes obesity and insulin resistance by activating the AhR/STAT3/IL-6 signaling.

Aberrant amino acid metabolism is a common event in obesity. Particularly, subjects with obesity are characterized by the excessive plasma kynurenine (Kyn). However, the primary source of Kyn and its impact on metabolic syndrome are yet to be fully addressed. Herein, we show that the overexpressed indoleamine 2,3-dioxygenase 1 (IDO1) in adipocytes predominantly contributes to the excessive Kyn, indicating a central role of adipocytes in Kyn metabolism. Depletion of Ido1 in adipocytes abrogates Kyn accumulation, protecting mice against obesity. Mechanistically, Kyn impairs lipid homeostasis in adipocytes via activating the aryl hydrocarbon receptor (AhR)/Signal transducer and activator of transcription 3 /interleukin-6 signaling. Genetic ablation of AhR in adipocytes abolishes the effect of Kyn. Moreover, supplementation of vitamin B6 ameliorated Kyn accumulation, protecting mice from obesity. Collectively, our data support that adipocytes are the primary source of increased circulating Kyn, while elimination of accumulated Kyn could be a viable strategy against obesity.

Pyrotinib plus capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases (PERMEATE): a multicentre, single-arm, two-cohort, phase 2 trial.

BACKGROUND: Patients with HER2-positive metastatic breast cancer have a high risk of developing brain metastases. Efficacious treatment options are scarce. We investigated the activity and safety of pyrotinib plus capecitabine in patients with HER2-positive metastatic breast cancer and brain metastases. METHODS: We did a multicentre, single-arm, two-cohort, phase 2 trial in eight tertiary hospitals in China. Patients aged 18 years or older who had radiotherapy-naive HER2-positive brain metastases (cohort A) or progressive disease after radiotherapy (cohort B), with an Eastern Cooperative Oncology Group performance status of 0-2, received pyrotinib 400 mg orally once daily, and capecitabine 1000 mg/m2 orally twice daily for 14 days, followed by 7 days off every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was confirmed intracranial objective response rate by investigator assessment according to the Response Evaluation Criteria In Solid Tumours (version 1.1). Activity and safety were analysed in patients with at least one dose of study drug. The study is ongoing, but recruitment is complete. The study is registered with ClinicalTrials.gov, NCT03691051. FINDINGS: Between Jan 29, 2019, and July 10, 2020, we enrolled 78 women: 51 (86%) of 59 patients in cohort A and 18 (95%) of 19 patients in cohort B had previous exposure to trastuzumab. Median follow-up duration was 15·7 months (IQR 9·7-19·0). The intracranial objective response rate was 74·6% (95% CI 61·6-85·0; 44 of 59 patients) in cohort A and 42·1% (20·3-66·5; eight of 19 patients) in cohort B. The most common grade 3 or worse treatment-emergent adverse event was diarrhoea (14 [24%] in cohort A and four [21%] in cohort B). Two (3%) patients in cohort A and three (16%) in cohort B had treatment-related serious adverse events. No treatment-related deaths occurred. INTERPRETATION: To our knowledge, this is the first prospective study showing the activity and safety of pyrotinib plus capecitabine in patients with HER2-positive breast cancer and brain metastases, especially in radiotherapy-naive population. This combination deserves further validation in a randomised, controlled trial. FUNDING: National Cancer Centre Climbing Foundation Key Project of China, Jiangsu Hengrui Pharmaceuticals. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Massoia Lactone Displays Strong Antifungal Property Against Many Crop Pathogens and Its Potential Application.

Massoia lactone could be released from liamocins produced by Aureobasidium melanogenum M39. The obtained Massoia lactone was very stable and highly active against many fungal crop pathogens which cause many plant diseases and food unsafety. Massoia lactone treatment not only could effectively inhibit their hyphal growth and spore germination, but also caused pore formation in cell membrane, reduction of ergosterol content, rise in intracellular ROS levels, and leakage of intracellular components, consequently leading to cellular necrosis and cell death. The direct contact of Massoia lactone with Fusarium graminearum spores could stop the development of Fusarium head blight symptom in the diseased wheats. Therefore, Massoia lactone could be a promising candidate for development as an effective and green bio-fungicide because of its high anti-fungal activity and the multiplicity of mode of its action.

Case Report: Effective Treatment With Pyrotinib and Capecitabine in a Heavily Pretreated Locally Advanced Breast Cancer Harboring Both HER2 Overexpression and Mutant.

The prognosis for female patients with locally advanced breast cancer (LABC) has improved with the emergence of novel drugs, especially for those who have HER2 overexpression or ERBB-2 amplification. Trastuzumab-based regimen has been the paradigm in guidelines as first-line therapy, whereas many patients got progressive disease after several cycles of treatment or rapidly progress because of primary resistance. Point mutations of ERBB2 gene occur in both HER2-amplication and non-amplification patients, with a 2% ratio in HER2 non-amplification cohort and 1.48% in HER2 amplication population. The acquired mutation ratio of ERBB2 substantially raised to 16.7%-17.7% in patients prior to trastuzumab treatment. ERBB2 mutation may be a critical reason of resistance and disease progression among the patients treated with anti-HER2 monoclonal trastuzumab or dual anti-HER2 antibodies with trastuzumab and pertuzumab, or tyrosine-kinase inhibitor. ERBB-2 mutation with L755S and V842I indicates resistance to trastuzumab, while that with L755S and K753I indicates resistance to lapatinib; these mutations maybe sensitive to pan-HER tyrosine-kinase inhibitors. A 48-year woman diagnosed with HER2-positive LABC developed trastuzumab resistance after three lines of trastuzumab cross-line treatment with partial response (PR) as the best response. The tissue was performed by next-generation sequencing (NGS), and the results discovered L755S in ERBB2 gene. Then, she received effective treatment with pyrotinib plus capecitabine and underwent mastectomy after six cycles of combined treatment with PR. Subsequently, breast mastectomy was performed, and she took pyrotinib plus capecitabine for 1 year and pyrotinib monotherapy for another 1 year as adjuvant therapy and achieved a long-term clinical benefit. In conclusion, pyrotinib is a potential neoadjuvant agent for patients who are heavily pretreated and harbor both ERBB2 amplification and ERBB2 mutant in locally advanced breast cancer.

Treatment of Pauwels type III femoral neck fracture with medial femoral neck support screw: a biomechanical and clinical study.

A femoral neck fracture is currently one of the most common types of fracture in clinical practice. The incidence continues to increase due to traffic accidents, trauma, and osteoporosis. This research includes a biomechanical study and a clinical retrospective study. In the biomechanical studies, three groups' effects (Control Group: 3CCS, DHS group, and study Group: 3CCS + mFNSS group) were compared by vertical compression tests, torsion tests, and fatigue tests. All the data were collected and analyzed. We subsequently performed a retrospective analysis of 131 patients with femoral neck fractures. The operative time, intraoperative blood loss, quality of postoperative fracture reduction, and follow-up observation of fracture healing, screw retreatment rates and fixation failure rates, as well as femoral head necrosis rates and hip function in two groups with 3CCS and 3CCS + mFNSS were compared. By the biomechanical study, we found that 3CCS + Mfnss group were biomechanically superior to 3CCS group and superior to the DHS group in terms of resistance to torsion. However, it was less effective than the DHS group in compressive strength and fatigue resistance. In terms of clinical application, 3CCS + mFNSS group was found to have lower screw retreatment rates and femoral head necrosis rates, and to have better fracture healing rates than group with 3CCS, indicating that medial support screws can effectively resist the vertical shear forces of fracture ends and promote the stability and healing of fracture ends, as well as to reduce the incidence of postoperative complications.

cAMP-PKA and HOG1 signaling pathways regulate liamocin production by different ways via the transcriptional activator Msn2 in Aureobasidium melanogenum.

Liamocins, as the secondary metabolites synthesized and secreted by Aureobasidium spp., consist of a single mannitol or a single arabitol head group partially O-acylated with three 3,5-dihydroxydecanoic ester groups or directly esterified with three or four 3,5-dihydroxydecanoic ester tails. Very recently, the whole synthetic pathway of liamocins in A. melanogenum 6-1-2 has been elucidated. It was found that the promoter sequences of all the genes related to liamocin synthesis in A. melanogenum 6-1-2 had stress regulatory elements with core sequences of AGGGG or CCCCT. Therefore, expression of all the genes would be regulated by the Msn2. In this study, it was found that removal of the single one MSN2 gene in A. melanogenum 6-1-2 made the mutant decrease yield of extracellular liamocin by 92.28 %, while complementation of the MSN2 gene in the mutant rendered liamocin synthesis to be restored. When A. melanogenum 6-1-2 was cultured in the liamocin fermentation medium with high glucose and low nitrogen, the Msn2 was localized in the nucleus and positively regulated the expression of the genes related to liamocin biosynthesis. Furthermore, when the key BCY1 gene encoding regulatory subunit of the cAMP-PKA signaling pathway in A. melanogenum 6-1-2 was knocked out, the amount of extracellular liamocins synthesized by the mutant was decreased by 96.73 % and the Msn2 was localized in the cytoplasm. Similarly, when the key HOG1 gene in the HOG1 signaling pathway was deleted, liamocin biosynthesis in the knockout strain was decreased by 98.09 %. However, it was found that the Hog1 may be one part of the general transcription complex to regulate the transcription of the MSN2 gene, leading to the reduced Msn2 and liamocin synthesis in the mutant. In addition, the key TOR1 gene and SNF1 gene in the TOR1 signaling pathway and the SNF1 signaling pathway were not involved in the regulation of the Msn2 activity and liamocin synthesis. It was concluded that the transcriptional activator Msn2, the HOG1 signaling pathway and the cAMP-PKA signaling pathway were involved in the regulation of liamocin biosynthesis and production.

Slc4 Gene Family in Spotted Sea Bass (Lateolabrax maculatus): Structure, Evolution, and Expression Profiling in Response to Alkalinity Stress and Salinity Changes.

The solute carrier 4 (SLC4) family is a class of cell membranes transporters involved in base transport that plays crucial roles in diverse physiological processes. In our study, 15 slc4 genes were identified and annotated in spotted sea bass, including five members of Cl-/HCO3- exchangers, eight genes coding Na+-dependent HCO3- transporters, and two copies of Na+-coupled borate transporters. The gene sequence and structure, chromosomal and syntenic arrangement, phylogenetic and evolution profiles were analyzed. Results showed that the slc4 gene in teleosts obviously expanded compared with higher vertebrates, arising from teleost-specific whole genome duplication event. Most gene sites of slc4 in spotted sea bass were under strong purifying selection during evolution, while positive selection sites were only detected in slc4a1b, slc4a8, and slc4a10b. Additionally, qRT-PCR results showed that different slc4 genes exhibited distinct branchial expression patterns after alkalinity and salinity stresses, of which the strongly responsive members may play essential roles during these physiological processes. Our study provides the systemic overview of the slc4 gene family in spotted sea bass and enables a better understanding for the evolution of this family and further deciphering the biological roles in maintaining ion and acid-base homeostasis in teleosts.

Evaluation of the ß-barrel outer membrane protein VP1243 as a candidate antigen for a cross-protective vaccine against Vibrio infections.

Vibrio parahaemolyticus is a Gram-negative halophilic bacterium that causes acute gastroenteritis after the consumption of contaminated food, wound infection, and seizures. Antibiotic therapy is the main method for controlling Vibrio infections, which inevitably leads to drug resistance. Therefore, a vaccine is urgently needed to avoid this problem. Outer membrane proteins (OMPs) play a pivotal role in the interaction between the host immune system and bacteria. VP1243 is an OMP of V. parahaemolyticus, and it possessed immunogenicity in our previous study. The present study found that VP1243 was widely distributed, highly conserved and possessed similar surface epitopes among the major Vibrio species. The protein stimulated a strong antibody response and induced cross-reactive immune responses in V. parahaemolyticus, V. alginolyticus and V. vulnificus. Notably, it provided 100% immune protection against lethal challenges by the three Vibrio species in mice immunized with VP1243. Efficient clearance of cells of the three Vibrio bacterial species was observed in immunized mice. These findings provide solid evidence for VP1243 as a promising candidate for the development of a versatile vaccine to protect against Vibrio infections.

Periodically ordered mesoporous iron phosphide for highly efficient electrochemical hydrogen evolution.

There is a pressing demand to explore alternative to Pt-based electrocatalysts for hydrogen evolution reaction (HER) in water electrolysis. In this study, an iron phosphide catalyst with periodically ordered mesoporous structure (meso-FeP) was fabricated via a nanocasting method for the HER. The as-prepared meso-FeP exhibited high electrocatalytic activity, affording 10 mA·cm-2 current density at small overpotentials of 114 mV and 136 mV with the maintenance of its catalytic activity for at least 22 h in 0.5 M H2SO4 and 1.0 M KOH, respectively. The outstanding performance is attributed to the high specific surface area (209.4 m2 g-1) derived from ordered mesopores, which endows the catalyst with abundant electrochemically active sites and accessible mass transport pathway. This work provides an efficient strategy to prepare mesoporous phosphides as high-performance hydrogen evolution catalysts.

Genetic evidences for the core biosynthesis pathway, regulation, transport and secretion of liamocins in yeast-like fungal cells.

So far, it has been still unknown how liamocins are biosynthesized, regulated, transported and secreted. In this study, a highly reducing polyketide synthase (HR-PKS), a mannitol-1-phosphate dehydrogenase (MPDH), a mannitol dehydrogenase (MtDH), an arabitol dehydrogenase (ArDH) and an esterase (Est1) were found to be closely related to core biosynthesis of extracellular liamocins in Aureobasidium melanogenum 6-1-2. The HR-PKS was responsible for biosynthesis of 3,5-dihydroxydecanoic acid. The MPDH and MtDH were implicated in mannitol biosynthesis and the ArDH was involved in arabitol biosynthesis. The Est1 catalyzed ester bond formation of them. A phosphopantetheine transferase (PPTase) activated the HR-PKS and a transcriptional activator Ga11 activated expression of the PKS1 gene. Therefore, deletion of the PKS1 gene, all the three genes encoding MPDH, MtDH and ArDH, the EST1, the gene responsible for PPTase and the gene for Ga11 made all the disruptants (Δpks13, Δpta13, Δest1, Δp12 and Δg11) totally lose the ability to produce any liamocins. A GLTP gene encoding a glycolipid transporter and a MDR1 gene encoding an ABC transporter took part in transport and secretion of the produced liamocins into medium. Removal of the GLTP gene and the MDR1 gene resulted in a Δgltp1 mutant and a Δmdr16 mutant, respectively, that lost the partial ability to secrete liamocins, but which cells were swollen and intracellular lipid accumulation was greatly enhanced. Hydrolysis of liamocins released 3,5-dihydroxydecanoic acid, mannitol, arabitol and acetic acid. We proposed a core biosynthesis pathway, regulation, transport and secretion of liamocins in A. melanogenum.

OmpW is positively regulated by iron via Fur, and negatively regulated by SoxS contribution to oxidative stress resistance in Escherichia coli.

Iron plays a central role at the interface of pathogen and host. The ability to sequester iron from a host not only reduces host immune defenses but also promotes pathogen virulence, leading to the occurrence of infectious disease. Recently, outer membrane protein OmpW was shown to protect bacteria against harsh environmental conditions and to play a role in infectious disease. The expression of this versatile protein is controlled by iron, but the underlying mechanism of iron regulation has not been elucidated. In this study, the relation between OmpW expression and iron was investigated. Our results demonstrated that expression of OmpW is responsive to iron. Iron uptake analysis showed that an ompW mutant strain has a strong requirement for iron as compared to wild type and the ompW complemented strain. Moreover, ferric uptake regulation protein Fur, an iron binding transcriptional factor, was downregulated under iron limitation conditions and had a similar expression profile to OmpW in the presence or absence of iron. Based on these results, we suggest that iron regulates OmpW by binding to Fur. Furthermore, SoxS, a transcriptional factor involved in oxidative stress, was found to negatively regulate OmpW. We found that downregulating or knocking out OmpW results in bacterial resistance to oxidative stress. These findings provide new insight into the regulation of OmpW expression by iron, and may represent a new mechanism contributing to iron-mediated infectious disease.

Network-based approach to identify biomarkers predicting response and prognosis for HER2-negative breast cancer treatment with taxane-anthracycline neoadjuvant chemotherapy.

OBJECTIVE: This study aims to identify effective gene networks and biomarkers to predict response and prognosis for HER2-negative breast cancer patients who received sequential taxane-anthracycline neoadjuvant chemotherapy. MATERIALS AND METHODS: Transcriptome data of training dataset including 310 HER2-negative breast cancer who received taxane-anthracycline treatment and an independent validation set with 198 samples were analyzed by weighted gene co-expression network analysis (WGCNA) approach in R language. Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were performed for the selected genes. Module-clinical trait relationships were analyzed to explore the genes and pathways that associated with clinicopathological parameters. Log-rank tests and COX regression were used to identify the prognosis-related genes. RESULTS: We found a significant correlation of an expression module with distant relapse-free survival (HR = 0.213, 95% CI [0.131-0.347], P = 4.80E-9). This blue module contained genes enriched in biological process of hormone levels regulation, reproductive system, response to estradiol, cell growth and mammary gland development as well as pathways including estrogen, apelin, cAMP, the PPAR signaling pathway and fatty acid metabolism. From this module, we further screened and validated six hub genes (CA12, FOXA1, MLPH, XBP1, GATA3 and MAGED2), the expression of which were significantly associated with both better chemotherapeutic response and favorable survival for BC patients. CONCLUSION: We used WGCNA approach to reveal a gene network that regulate HER2-negative breast cancer treatment with taxane-anthracycline neoadjuvant chemotherapy, which enriched in pathways of estrogen signaling, apelin signaling, cAMP signaling, the PPAR signaling pathway and fatty acid metabolism. In addition, genes of CA12, FOXA1, MLPH, XBP1, GATA3 and MAGED2 might serve as novel biomarkers predicting chemotherapeutic response and prognosis for HER2-negative breast cancer.

Effectiveness of the new integrated strategy to control the transmission of Schistosoma japonicum in China: a systematic review and meta-analysis.

Since 2004, the national schistosomiasis control strategy in China has shifted from the morbidity control strategy (conventional strategy) to an integrated strategy (new strategy). We investigated the effectiveness of the new strategy and compared it against the conventional strategy. We retrieved from electronic databases the literature regarding the new strategy published from 2000 to 2017. The effect of the new or conventional strategy on infection by Schistosoma japonicum of humans and snails (Oncomelania hupensis) was evaluated with pooled log relative risk (logRR). A total of only eight eligible publications were included in the final meta-analysis. The results showed that implementation of the new strategy reduced the infection risk by 3-4 times relative to the conventional strategy. More specifically, the conventional strategy caused a reduction in both human (logRR = 0.56, 95% CI: 0.12-0.99) and snail infections (logRR = 0.34, 95% CI: -0.69-1.37), while the new strategy also significantly reduced both human (logRR = 1.89, 95% CI: 1.33-2.46) and snail infections (logRR = 1.61, 95% CI: 1.06-2.15). In contrast to the conventional strategy, the new strategy appeared more effective to control both human (logRR difference = 1.32, 95% CI: 0.78-1.86) and snail infections (logRR difference = 1.53, 95% CI: 0.76-2.31). Our data demonstrate that the new integrated strategy is highly effective to control the transmission of S. japonicum in China, and this strategy is recommended for schistosomiasis elimination in other affected regions across the world, with adaptation to local conditions.

Heterogeneous Nanostructure Based on 1T-Phase MoS2 for Enhanced Electrocatalytic Hydrogen Evolution.

As an electrocatalyst, conventional 2H-phase MoS2 suffers from limited active sites and inherently low electroconductivity. Phase transitions from 2H to 1T have been proposed as an effective strategy for optimization of the catalytic activity. However, complicated chemical exfoliation is generally involved. Here, MoS2 heterogeneous-phase nanosheets with a 1T phase (1T/2H-MoS2) generated in situ were prepared through a facile hydrothermal method. The locally introduced 1T-phase MoS2 can not only contribute more active sites but also markedly promote the electronic conductivity. Because of this unique structure, the as-synthesized 1T/2H-MoS2 nanosheets exhibit remarkable performance for the hydrogen evolution reaction with a small overpotential of 220 mV at 10 mA/cm2, a small Tafel slope of 61 mV/decade, and robust stability. This work facilitates the development of a two-dimensional heterogeneous nanostructure with enhanced applications.