Hepatic steatosis predicts metachronous liver metastasis in colorectal cancer patients: a nested case-control study and systematic review.

Nearly twenty-five percent of colorectal cancer (CRC) patients develop metachronous colorectal liver metastasis (CRLM) after curative surgery. Hepatosteatosis is the most prevalent liver condition worldwide, but its impact on the incidence of metachronous CRLM is understudied. In the present study, we aimed to investigate the predictive value of hepatic steatosis on the development of metachronous CRLM. First, a nested case-control study was conducted, enrolling stage I to III CRC patients in the National Colorectal Cancer Cohort (NCRCC) database. Metachronous CRLM patients and recurrence-free patients were matched via propensity-score matching. Fatty liver was identified based on treatment-naïve CT scans and the degree of hepatic fibrosis was scored. Multivariable analysis was conducted to investigate the association between fatty liver and metachronous CRLM. In our database, a total of 414 patients were included. Metachronous CRLM patients had considerably higher rates of hepatic steatosis (30.9% versus 15.9%, P<0.001) and highly fibrotic liver (11.6% versus 2.9%, P=0.001) compared to recurrence-free patients. Multivariable analysis showed that fatty liver (odds ratios [OR]=1.99, 95% confidence interval [CI] 1.19-3.30, P=0.008) and fibrotic liver (OR=4.27, 95% CI 1.54-11.81, P=0.005) were associated with high risk of metachronous CRLM. Further, a systematic literature review was performed to assess available evidence on the association between hepatosteatosis and development of metachronous CRLM. In the systematic review, 1815 patients were pooled from eligible studies, and hepatic steatosis remained a significant risk factor for metachronous CRLM (OR=1.90, 95% CI 1.35-2.66, P<0.001, I2=25.3%). In conclusion, our data suggest that patients with a steatotic liver and a high fibrosis score at CRC diagnosis have elevated risk of developing metachronous CRLM.

Relationship between Protein-Induced Membrane Curvature and Membrane Thermal Undulation.

This work studied the membrane curvature generated by anchored proteins lacking amphipathic helices and intrinsic morphologies, including the Epsin N-terminal homology domain, intrinsically disordered C-terminal domain, and truncated C-terminal fragments, by using coarse-grained molecular dynamics simulations. We found that anchored proteins can stabilize the thermal undulation of membranes at a wavelength five times the protein's binding size. This proportional connection is governed by the membrane bending rigidity and protein density. Extended intrinsically disordered proteins with relatively high hydrophobicity favor colliding with the membrane, leading to a much larger binding size, and show superiority in generating membrane curvature at low density over folded proteins.

Compact Combustion Mechanisms of Typical n-Alkanes Developed by the Minimized Reaction Network Method.

The existing combustion kinetic modeling method which aims at developing phenomenological combustion mechanisms characterized by multiple reactions confronts several challenges, including the conflicts between computing resources and mechanism scales during numerical simulation, etc. In order to address these issues, the minimized reaction network method for complex combustion system modeling based on the principle of simultaneous chemical equilibrium is proposed, which is aimed to develop combustion mechanisms with minimal reaction steps under a limited number of species. The concept of mechanism resolution is proposed in this method, and the reaction network with minimal reaction steps under a given mechanism resolution is constructed so that the scale of mechanisms is compressed greatly. Meanwhile, distinguishing from other mechanisms, the reversible form of elementary reactions is adopted and the classical two-parameter (A, Ea) Arrhenius equation fits the rate constants. Typical n-alkanes including n-butane, n-heptane, n-octane, n-decane, n-dodecane and n-hexadecane were taken as examples to indicate the development process of mechanisms and systematic kinetic validations were carried out. Results show that this method leads to very compact mechanisms with satisfactory accuracy, and it eliminates the process of mechanism reduction and is beneficial for mechanism optimization. This method and the derived kinetic mechanisms are hoped to contribute to combustion engineering applications.

The efficacy and safety of anti-EGFR target agents in patients with potentially resectable metastatic colorectal cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: Adding anti-epidermal growth factor receptor (anti-EGFR) target agents to conversion therapy may improve the resection rates and survival of patients with potentially resectable metastatic colorectal cancer (mCRC). This study aims to analyze the efficacy and safety of additional anti-EGFR target agents. METHODS: A systematic search was conducted on PubMed, Web of Science, Embase, and Cochrane Library. And all relevant studies published in English before January 2023 were collected to explore the impact of additional anti-EGFR targeted agent on the efficacy and safety of patients with potentially resectable mCRC (PROSPERO: CRD42022340523, https://www.crd.york.ac.uk/PROSPERO/ ). RESULTS: This study included a total of 8 articles, including 2618 patients. The overall response rate (ORR) and R0 resection rates of the experimental group were higher than those of the control group, while there was no significant difference in progression-free survival (PFS) and overall survival (OS) between the two groups. In RAS/KRAS wild-type patients, the ORR (RR: 1.20, 95% Cl: 1.02-1.41, p = 0.03), R0 resection rate (RR: 1.60, 95% Cl: 1.17-2.20, p = 0.003), PFS (HR: 0.80, 95% Cl: 0.68-0.93, p = 0.003), and OS (HR: 0.87, 95% Cl: 0.76-0.99, p = 0.031) of the experimental group were higher than those of the control group. While in KRAS mutant patients, there was no statistical difference between the two groups in ORR, R0 resection rate, PFS, and OS. CONCLUSION: The addition of anti-EGFR targeted agents can improve the prognosis of RAS/KRAS wild-type patients with potentially resectable mCRC, while KRAS mutant patients may not benefit. In addition, the overall safety factor was controllable.

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

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

Mechanisms and energetics of benzophenone photosensitized thymine damage and repair from Paternò-Büchi cycloaddition.

Here, we report the detailed mechanisms of benzophenone (BZP) photosensitized thymine damage and repair by Paternò-Büchi (PB) cycloaddition. It was found that the head-to-head and head-to-tail PB cycloadditions lead to the formation of the C-O bonds in the 3(nπ*) state and the 3(ππ*) state, respectively. The conical intersection occurs before the head-to-tail C-O bonding. Then, the C-C bonds are formed via intersystem crossing (ISC). The C-O bonding is the rate-determining step of PB cycloaddition. For the cycloreversion reactions, the ring-opening processes completely occur in the singlet excited states of oxetanes. The head-to-head oxetane goes through a conical intersection before cycloreversion with a little energy barrier of 1.8 kcal mol-1. The head-to-tail oxetane splits without a barrier. Then, the ISC processes take place to restore thymine. Throughout the ring-closing and ring-opening processes, ISC plays an important role. These findings are in good agreement with the available experimental findings. We hope that this comprehensive work can provide a deeper understanding of photosensitive DNA damage and repair.

Mechanisms and energetics for hydrogen abstraction of thymine photosensitized by benzophenone from theoretical principles.

The significant role of hydrogen abstraction in chemistry and biology has inspired many theoretical works to link its practical phenomena and mechanistic properties. Here, the photophysical processes and hydrogen abstraction mechanisms of benzophenone (BZP) photosensitized thymine damage were systematically investigated from theoretical principles. It was found that the BZP photosensitizer upon UV irradiation undergoes vertical excitation, internal conversion, vibrational relaxation and intersystem crossing into a triplet excited state. Then the triplet BZP damages thymine by a hydrogen abstraction process. However, the reverse reaction easily occurs due to the lower reaction energy, which causes a low yield of hydrogen abstraction products. We hope this comprehensive work can provide a deeper understanding of photosensitive DNA damage from hydrogen abstraction.

Modeling of Sandia Flame D with the non-adiabatic chemistry tabulation approach: the effects of different laminar flames on NO X prediction.

The effects of different one-dimensional laminar flames on the prediction of nitrogen oxide (NO X ) emission in Sandia Flame D are numerically investigated using a flamelet method in the present work. In addition to the basic control variables of the mixture fraction and the reaction progress variable for chemistry tabulation in this combustion model, two additional variables of mixture fraction variance and enthalpy loss are added to the control variable space to improve prediction accuracy of the NO X pollutant. The former variable of mixture fraction variance is used for the presumed probability density function integration, and the latter takes into account the non-adiabatic effect. Two flamelet libraries are generated based on the one-dimensional unstretched premixed flame and the one-dimensional counterflow diffusion flame, respectively. An additional transport equation for the mass fraction of nitrogen oxide (NO) is solved for improving prediction accuracy. The unsteady Reynolds-averaged Navier-Stokes (URANS) simulation results are compared and analyzed with experimental data. The simulation results show dependence on the type of laminar flame. In the four-dimensional control variable space, the results with steady unstretched premixed flame indicate great agreement on the predictions of temperature and NO field. The computational method proposed in the present work sheds light on the high-precision combustion numerical simulation of NO X emission.

Anti-HIV Potential of Beesioside I Derivatives as Maturation Inhibitors: Synthesis, 3D-QSAR, Molecular Docking and Molecular Dynamics Simulations.

HIV-1 maturation is the final step in the retroviral lifecycle that is regulated by the proteolytic cleavage of the Gag precursor protein. As a first-in-class HIV-1 maturation inhibitor (MI), bevirimat blocks virion maturation by disrupting capsid-spacer peptide 1 (CA-SP1) cleavage, which acts as the target of MIs. Previous alterations of beesioside I (1) produced (20S,24S)-15ꞵ,16ꞵ-diacetoxy-18,24; 20,24-diepoxy-9,19-cyclolanostane-3ꞵ,25-diol 3-O-3',3'-dimethylsuccinate (3, DSC), showing similar anti-HIV potency compared to bevirimat. To ascertain the binding modes of this derivative, further modification of compound 1 was conducted. Three-dimensional quantitative structure−activity relationship (3D-QSAR) analysis combined with docking simulations and molecular dynamics (MD) were conducted. Five new derivatives were synthesized, among which compound 3b showed significant activity against HIV-1NL4-3 with an EC50 value of 0.28 µM. The developed 3D-QSAR model resulted in great predictive ability with training set (r2 = 0.99, q2 = 0.55). Molecular docking studies were complementary to the 3D-QSAR analysis, showing that DSC was differently bound to CA-SP1 with higher affinity than that of bevirimat. MD studies revealed that the complex of the ligand and the protein was stable, with root mean square deviation (RMSD) values <2.5 Å. The above results provided valuable insights into the potential of DSC as a prototype to develop new antiviral agents.

Two new cycloartane triterpenoid glycosides from the rhizomes of Actaea vaginata.

Two new cycloartane triterpenoid glycosides, soulieoside V (1) and 15-deacetylbeesioside O (2), together with one known compound, beesioside J (3), were isolated from the ethanolic extract of the rhizomes of Actaea vaginata. Their structures were elucidated by spectroscopic methods and by comparison with data reported in the literature. All the compounds were tested for their cytotoxic activities against human cancer cell lines.

Effect of Neoadjuvant Therapy on the Functional Outcome of Patients With Rectal Cancer: A Systematic Review and Meta-Analysis.

AIMS: The impact of neoadjuvant therapy on the functional outcome of patients with resectable rectal cancer is still controversial. The aim of the present study was to explore the effects of neoadjuvant therapy on anorectal function (ARF), urinary function and sexual function in relevant patients. MATERIALS AND METHODS: PubMed, Embase, Web of Science and the Cochrane Library were searched systematically. All English-language studies, published from January 2000 to July 2021, that explored the (postoperative) effects of neoadjuvant therapy versus upfront surgery on ARF, urinary function and sexual function of patients were included (PROSPERO 2021: CRD42021281617). RESULTS: The data in this study were derived from 37 articles based on 33 studies; in total, 17 917 patients were enrolled. The meta-analysis revealed that the incidence of anorectal dysfunction in the neoadjuvant therapy group was significantly higher than that in the group of upfront surgery, which was manifested by a higher incidence of major low anterior resection syndrome (odds ratio = 3.09, 95% confidence interval = 2.48, 3.84; P < 0.001), reduction of mean squeeze pressure and mean resting pressure, and other manifestations, including clustering of stools, incontinence, urgency and use of pads. With the extension of follow-up time, the adverse effects of neoadjuvant therapy on major low anterior resection syndrome existed. Compared with patients undergoing upfront surgery, neoadjuvant therapy increased the risk of urinary incontinence (odds ratio = 1.31, 95% confidence interval = 1.00, 1.72; P = 0.05) and erectile dysfunction (odds ratio = 1.77, 95% confidence interval = 1.27, 2.45; P < 0.001). CONCLUSION: Compared with upfront surgery, neoadjuvant therapy is not only associated with impairment of ARF, but also with increased incidence of urinary incontinence and male erectile dysfunction. However, the influence of confounding factors (e.g. surgical method, tumour stage) needs to be considered.

Thermodynamic Driving Forces for Divalent Cations Binding to Zwitterionic Phospholipid Membranes.

We calculated the free energies for calcium, magnesium, and zinc ions binding to a zwitterionic phospholipid bilayer by using molecular dynamics simulations and the enhanced umbrella sampling technique. By decomposing the free energy into entropic and enthalpic contributions, we found that Ca2+ has the highest binding affinity and that the overall process is endothermic combined with a secondary exothermic process at higher ion concentrations. The relatively low dehydration free energy of Ca2+ allows it to release coordinated water upon binding to the membrane. The dehydrated Ca2+ further coordinates with lipids, resulting in a weaker influence on the water orientation and increased entropy. However, when sufficient Ca2+ ions are adsorbed, the concentrated cation layer induces a positive electrostatic field, which enhances the energy barrier for further ion binding and orients the adjacent water, resulting in decreased entropy. In contrast, binding of Mg2+ and Zn2+ is exothermic and less favored because they remain fully hydrated when interacting with lipids.

Hydrophobicity Determines the Bacterial Killing Rate of α-Helical Antimicrobial Peptides and Influences the Bacterial Resistance Development.

Rapid antimicrobial action is an important advantage of antimicrobial peptides (AMPs) over antibiotics, which is also a reason for AMPs being less likely to induce bacterial resistance. However, the structural parameters and underlying mechanisms affecting the bacterial killing rate of AMPs remain unknown. In this study, we performed a structure-activity relationship (SAR) study using As-CATH4 and 5 as templates. We revealed that hydrophobicity, rather than other characteristics, is the critical structural parameter determining the bacterial killing rate of α-helical AMPs. With the hydrophobicity increase, the action rates of AMPs including bacterial binding, lipopolysaccharides neutralization, and outer and inner membrane permeabilization increased. Additionally, the higher hydrophobic AMPs with enhanced bacterial killing rates possess better in vivo therapeutic potency and a lower propensity to induce bacterial resistance. These findings revealed the importance of the bacterial killing rate for AMPs and are of great significance to the design and optimization of AMP-related drugs.

The relationship between tobacco and breast cancer incidence: A systematic review and meta-analysis of observational studies.

Background: The effect of tobacco on breast cancer (BC) is controversial. The purpose of this study was to investigate the relationship between tobacco and BC. Methods: A search was conducted in PubMed, EBSCO, Web of Science and Cochrane Library databases before February 2022. The adjusted odd ratio (OR) and corresponding 95% confidence interval (CI) were used to examine the relationship between active or passive smoking and BC risk. Results: A total of 77 articles composed of 2,326,987 participants were included for this meta-analysis. Active (OR=1.15, 95% CI=1.11-1.20, p<0.001) and passive (OR=1.17, 95% CI=1.09-1.24, p<0.001) smoking increased the risk of BC in the female population, especially premenopausal BC (active smoking: OR=1.24, p<0.001; passive smoking: OR=1.29, p<0.001), but had no effect on postmenopausal BC (active smoking: OR=1.03, p=0.314; passive smoking: OR=1.13, p=0.218). Active smoking increased the risk of estrogen receptor-positive (ER+) BC risk (OR=1.13, p<0.001), but had no effect on estrogen receptor-negative (ER-) BC (OR=1.08, p=0.155). The risk of BC was positively associated with the duration and intensity of smoking, negatively associated with the duration of smoking cessation. Active smoking increased the risk of BC in the multiparous population (OR=1.13, p<0.001), but had no effect on the nulliparous population (OR=1.05, p=0.432), and smoking before the first birth (OR=1.22, 95% CI=1.17-1.27) had a greater impact on the risk of BC than smoking after the first birth (OR=1.08, 95% CI=1.04-1.12). Conclusion: Smoking (active and passive) increased the risk of BC in women. The effect of smoking on BC was influenced by smoking-related factors (duration, intensity, years of quitting), population-related factors (fertility status), and BC subtypes. Systematic Review Registration: identifier CRD42022322699.

Cytotoxic cycloartane triterpenoid saponins from Actaea vaginata and their mechanism of action.

A further phytochemical investigation of the whole plants of Actaea vaginata afforded two new cycloartane triterpenoid saponins, (20S*,24R*)-15α,16ß-diacetoxy-20,24-epoxy-9,19-cyclolanostane-3ß,25-diol-3-O-ß-d-xylopyranoside (1) and (20S)-15ß,16ß -diacetoxy-18,20-epoxy-3ß,25-diol-24-oxo-9,19-cyclolanostan-3-O-ß-D-xylo-pyrano-syl-25-O-ß-d-glucopyranoside (2), together with four known compounds (3-6). Their structures were established on the basis of extensive analysis of NMR and HRESIMS data as well as by comparison with the reported data in the literature. All the isolates were evaluated for their cytotoxic activities against human hepatocellular carcinoma HepG2 cell line. Compounds 1 and 2 exhibited weak cytotoxicity with IC50 values of 36.10 and 27.39 µM, respectively. In addition, beesioside I (6) was found to significantly inhibit proliferation and induce apoptosis in HepG2 cells. A closer examination of underlying mechanism revealed that beesioside I could increase the levels of ROS and caspase-3 and promote phosphorylation of JNK in the JNK signaling pathway. Molecular modeling studies also shed further light on how beesioside I interacted with the key protein kinase.

Polymyxins induce lipid scrambling and disrupt the homeostasis of Gram-negative bacteria membrane.

Polymyxins are increasingly used as the last-line therapeutic option for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. However, efforts to address the resistance in superbugs are compromised by a poor understanding of the bactericidal modes because high-resolution detection of the cell structure is still lacking. By performing molecular dynamics simulations at a coarse-grained level, here we show that polymyxin B (PmB) disrupts Gram-negative bacterial membranes by altering lipid homeostasis and asymmetry. We found that the binding of PmBs onto the asymmetric outer membrane (OM) loosens the packing of lipopolysaccharides (LPS) and induces unbalanced bending torque between the inner and outer leaflets, which in turn triggers phospholipids to flip from the inner leaflet to the outer leaflet to compensate for the stress deformation. Meanwhile, some LPSs may be detained on the inner membrane (IM). Then, the lipid-scrambled OM undergoes phase separation. Defects are created at the boundaries between LPS-rich domains and phospholipid-rich domains, which consequently facilitate the uptake of PmB across the OM. Finally, PmBs target LPSs detained on the IM and similarly perturb the IM. This lipid Scramble, membrane phase Separation, and peptide Translocation model depicts a novel mechanism by which polymyxins kill bacteria and sheds light on developing a new generation of polymyxins or antibiotic adjuvants with improved killing activities and higher therapeutic indices.

Numerical Investigations on the Molecular Reaction Model for Thermal Cracking of n-Decane at Supercritical Pressures.

The pyrolysis of endothermic hydrocarbon fuel plays a vital role in regenerative cooling channels. Based on previous experiments and mechanism models of n-decane, and considering the impact of the secondary reaction at high conversion, the present work establishes a cracking reaction model of n-decane containing 16 species and 26 reactions. One-dimensional plug flow reactor simulation verifies that the model has high accuracy in predicting species distribution. The high-accuracy model is applied to the computational fluid dynamics (CFD) simulation of the supercritical cracking heat transfer, and compared with the results of a one-step global model as the chemistry model. The results show that the high-accuracy model is more accurate in terms of fuel conversion, temperature, and product distribution. Furthermore, the reasons for the difference of the two chemistry models in the CFD simulation are analyzed from the perspective of chemical kinetics. The new model generates more products of small molecules due to the consideration of secondary reactions. However, for the one-step model, it mainly cracked into large molecules even at high conversion. The product distribution affects the chemical endotherm and then the fuel temperature, which in turn affects the reaction rate and finally the conversion of the fuel. In addition, pyrolysis affects the properties of the fuel, which in turn affects the convective heat transfer. Among the several influencing factors of heat transfer, the correction factor of isobaric specific heat, which is the ratio of the specific heat of fluid to the average specific heat, can well reflect the changing trend of the convective heat transfer coefficient. The present work demonstrates the important role of the kinetic model in the simulation of the supercritical cracking heat transfer process, and the corresponding methods can be used in the design of regenerative cooling systems.

Relationship Between SGLT-2i and Ocular Diseases in Patients With Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials.

Background: This meta-analysis was conducted to explore the association between sodium-glucose cotransporter 2 inhibitors (SGLT-2is) and ocular diseases in type 2 diabetes mellitus (T2DM) patients. Methods: PubMed, Cochrane Central Registry of Controlled Trials, Web of Science and Springer were searched for articles on randomized controlled trials (RCTs) involving T2DM patients treated with SGLT-2i versus placebo or other hypoglycemic agents published prior to August 2021. The primary outcome of this meta-analysis was incidence of ocular diseases, which was assessed using risk ratios (RR) and 95% confidence intervals (CI). We reviewed 47 papers and compared the effect of SGLT-2i with the effect of the control groups (placebo and other hypoglycemic drugs) on the incidence of ocular diseases. Results: Compared with controls, overall SGLT-2i use in T2DM patients was not associated with incidences of cataract, glaucoma, retinal disease and vitreous disease. Ertugliflozin (RR=0.47, P=0.01) reduced the risk for retinal disease, while empagliflozin (RR=0.44, P=0.05) reduced the risk for diabetic retinopathy (DR) compared with controls. SGLT-2i (RR=0.50, P=0.02), perhaps empagliflozin (RR=0.47, P=0.06), reduced the risk of retinal disease compared with active hypoglycemic agents. Canagliflozin (RR=4.50, P=0.03) increased the risk for vitreous disease compared with placebo. Conclusions: There was no significant correlation between overall SGLT-2i and ocular diseases (cataract, glaucoma, retinal disease, vitreous disease, corneal disease, conjunctival disease, uveal disease, eye haemorrhage and vision problems) in T2DM patients. Ertugliflozin and empagliflozin may protect against ocular diseases, but canagliflozin may promote ocular diseases.

The relationship between night shift work and breast cancer incidence: A systematic review and meta-analysis of observational studies.

The purpose of this study was to investigate the relationship between night shift work and breast cancer (BC) incidence. A search was performed in PubMed, EBSCO, Web of Science, and Cochrane Library databases before June 2021. The exposure factor of this study is night shift work, the primary outcome is the risk of BC. A total of 33 observational studies composed of 4,331,782 participants were included. Night shift work increases the risk of BC in the female population (hazard ratio [HR] = 1.20, 95% confidence interval [Cl] = 1.10-1.31, p < 0.001), especially receptor-positive BC, including estrogen receptor (ER)+ BC (HR = 1.35, p < 0.001), progesterone receptor (PR)+ BC (HR = 1.30, p = 0.003), and human epidermal growth factor receptor 2 (HER2)+ BC (HR = 1.42, p < 0.001), but has no effect on HER2- BC (HR = 1.10, p = 0.515) and ER-/PR- BC (HR = 0.98, p = 0.827). The risk of BC was positively correlated with night shift working duration, frequency, and cumulative times. For women who start night work before menopause, night work will increase the incidence of BC (HR = 1.17, p = 0.020), but for women who start night work after menopause, night work does not affect BC (HR = 1.04, p = 0.293). Night work can increase the incidence of BC in the female population. The effect of long working hours, frequency, and the cumulative number of night shifts on BC is influenced by menopausal status.

Composition and key-influencing factors of bacterial communities active in sulfur cycling of soda lake sediments.

Bacteria are important participants in sulfur cycle of the extremely haloalkaline environment, e.g. soda lake. The effects of physicochemical factors on the composition of sulfide-oxidizing bacteria (SOB) and sulfate-reducing bacteria (SRB) in soda lake have remained elusive. Here, we surveyed the community structure of total bacteria, SOB and SRB based on 16S rRNA, soxB and dsrB gene sequencing, respectively, in five soda lakes with different physicochemical factors. The results showed that the dominant bacteria belonged to the phyla Proteobacteria, Bacteroidetes, Halanaerobiaeota, Firmicutes and Actinobacteria. SOB and SRB were widely distributed in lakes with different physicochemical characteristics, and the community composition were different. In general, salinity and inorganic nitrogen sources (NH4+-N, NO3--N) were the most significant factors. Specifically, the communities of SOB, mainly including Thioalkalivibrio, Burkholderia, Paracoccus, Bradyrhizobium, and Hydrogenophaga genera, were remarkably influenced by the levels of NH4+-N and salinity. Yet, for SRB communities, including Desulfurivibrio, Candidatus Electrothrix, Desulfonatronospira, Desulfonatronum, Desulfonatronovibrio, Desulfonatronobacter and so on, the most significant determinants were salinity and NO3--N. Besides, Rhodoplanes played a significant role in the interaction between SOB and SRB. From our results, the knowledge regarding the community structures of SOB and SRB in extremely haloalkaline environment was extended.