Direct ammonia oxidation (Dirammox) is favored over cell growth in Alcaligenes ammonioxydans HO-1 to deal with the toxicity of ammonium.

Bacteria capable of direct ammonia oxidation (Dirammox) play important roles in global nitrogen cycling and nutrient removal from wastewater. Dirammox process, NH3 → NH2 OH → N2 , first defined in Alcaligenes ammonioxydans HO-1 and encoded by dnf gene cluster, has been found to widely exist in aquatic environments. However, because of multidrug resistance in Alcaligenes species, the key genes involved in the Dirammox pathway and the interaction between Dirammox process and the physiological state of Alcaligenes species remain unclear. In this work, ammonia removal via the redistribution of nitrogen between Dirammox and microbial growth in A. ammonioxydans HO-1, a model organism of Alcaligenes species, was investigated. The dnfA, dnfB, dnfC, and dnfR genes were found to play important roles in the Dirammox process in A. ammonioxydans HO-1, while dnfH, dnfG, and dnfD were not essential genes. Furthermore, an unexpected redistribution phenomenon for nitrogen between Dirammox and cell growth for ammonia removal in HO-1 was revealed. After the disruption of the Dirammox in HO-1, more consumed NH4 + was recovered as biomass-N via rapid metabolic response and upregulated expression of genes associated with ammonia transport and assimilation, tricarboxylic acid cycle, sulfur metabolism, ribosome synthesis, and other molecular functions. These findings deepen our understanding of the molecular mechanisms for Dirammox process in the genus Alcaligenes and provide useful information about the application of Alcaligenes species for ammonia-rich wastewater treatment.

Cytokine analysis of aqueous humor in patients with cytomegalovirus corneal endotheliitis.

PURPOSE: To evaluate cytokine levels of aqueous humor in patients with cytomegalovirus (CMV) corneal endotheliitis and their relationships with CMV DNA load. METHODS: 44 aqueous humor samples were obtained from 26 patients with CMV corneal endotheliitis at various stages of treatment. 33 samples obtained from cataract patients during the same period were selected as a control group. Each sample was used to measure the concentration of the CMV DNA load using real-time quantitative polymerase chain reaction, and to examine the levels of IL-6, IL-8, IL-10, MCP-1, VCAM-1, VEGF, IP-10, G-CSF, ICAM-1 and IFN-γ using a cytometric bead array. RESULTS: All 10 cytokines were found to have statistically significant differences between the CMV endotheliitis and cataract groups. The Spearman correlation test showed that the concentration of CMV DNA load was significantly associated with the levels of IL-6 (P = 0.005, r = 0.417), IL-8 (P < 0.001, r = 0.514), IL-10 (P < 0.001, r = 0.700), MCP-1 (P = 0.001, r = 0.487), VEGF (P < 0.001, r = 0.690), IP-10 (P = 0.001, r = 0.469), G-CSF (P < 0.001, r = 0.554) and ICAM-1 (P < 0.001, r = 0.635), but not significantly associated with VCAM-1 (P = 0.056) and IFN-γ (P = 0.219). CONCLUSIONS: There was a combined innate and adaptive immune response in aqueous humor in patients with CMV endotheliitis. Levels of multiple cytokines were significantly correlated with viral particle. Cytokines are potential indicators to help diagnose CMV endotheliitis, evaluate disease activity and assess treatment response.

Comparative Analysis of the Interfacial Structure and Properties of BiOX/BiOY (X, Y = F, Cl, Br, and I) Heterostructures through DFT Calculations.

This study focuses on the systematic investigation of the microstructure, interfacial energy, and electronic structure of six BiOX/BiOY heterostructures constructed using four bismuth oxyhalide materials. Utilizing density functional theory (DFT) calculations, the study provides fundamental insights into the interfacial structure and properties of these heterostructures. The results indicate that the formation energies of BiOX/BiOY heterostructures decrease in the order of BiOF/BiOI, BiOF/BiOBr, BiOF/BiOCl, BiOCl/BiOBr, BiOBr/BiOI, and BiOCl/BiOI. BiOCl/BiBr heterostructures were found to have the lowest formation energy and were the most easily formed. Conversely, the formation of BiOF/BiOY heterostructures was observed to be unstable and difficult to achieve. Furthermore, the interfacial electronic structure analysis revealed that BiOCl/BiOBr, BiOCl/BiOI, and BiOBr/BiOI displayed opposite electric fields that facilitated electron-hole pair separation. Therefore, these research findings provide a comprehensive understanding of the mechanisms underlying the formation of BiOX/BiOY heterostructures and present theoretical guidance for the design of innovative and efficient photocatalytic heterostructures, with an emphasis on BiOCl/BiOBr heterostructures. This study highlights the advantages of distinctively layered BiOX materials and their heterostructures, which offer a wide range of band gap values, and demonstrates their potential for various research and practical applications.

Endovascular repair of aortic pathologies involving the aortic arch using castor stent-graft combined with in-vitro fenestration technology.

BACKGROUND: Aortic arch pathologies are concerning clinical conditions with poor prognoses. The use of thoracic endovascular aortic repair (TEVAR) has been investigated to treat aortic arch pathologies. Nonetheless, cerebral blood flow regulation during endovascular aortic arch repair therapy remains challenging. Castor, a unique single-branched stent graft, has been proven effective for retaining the left subclavian artery (LSA). This study aimed to determine whether endovascular therapy for pathologies involving the aortic arch using Castor in combination with the in-vitro fenestration technique is promising, effective, and safe. METHODS: Eligible patients were enrolled between June 2018 and December 2021. All patients underwent TEVAR with an evaluated proximal landing zone for "Castor" located in Ishimaru zones 0-1. Moreover, the supra-aortic branches (SABs) were reconstructed using the Castor in combination with the in-vitro fenestration technique. RESULTS: Herein, 57 patients with aortic arch lesions were treated with Castor in combination with the in-vitro fenestration technique. Innominate artery and the left carotid artery (LCA) were reconstructed in 5 patients, LCA and left subclavian artery (LSA) were reconstructed in 22 patients, and the total SABs were effectively reconstructed in 30 patients (including a hybrid arch repair case). Among them (excluding a hybrid arch repair case) were in-vitro fenestration methodologies for LCA in 32 of 34 cases (2 switched to in-situ fenestration) and LSA in 51 of 56 cases (3 switched to in-situ fenestration and 2 converted to spring coil caulking); furthermore, LCA and LSA in-vitro fenestration were simultaneously successfully performed in 27 of 34 cases. There were no surgical-related neurological complications, and early mortality was estimated at 5.26%. At a mean follow-up of 3.75 months, computed tomography (CTA) images confirmed that each branch stent remained patent. There were no signs of endoleaks, migrative manifestations, or the need for secondary endovascular intervention or conversion to open surgical procedures. CONCLUSION: Castor, in combination with in-vitro fenestration, reflects a feasible, efficient procedure for re-developing SABs.

Detection and Quantification of Antimicrobial-Resistant Cells in Aquatic Environments by Bioorthogonal Noncanonical Amino Acid Tagging.

Aquatic environments are important reservoirs of antibiotic wastes, antibiotic resistance genes, and bacteria, enabling the persistence and proliferation of antibiotic resistance in different bacterial populations. To prevent the spread of antibiotic resistance, effective approaches to detect antimicrobial susceptibility in aquatic environments are highly desired. In this work, we adopt a metabolism-based bioorthogonal noncanonical amino acid tagging (BONCAT) method to detect, visualize, and quantify active antimicrobial-resistant bacteria in water samples by exploiting the differences in bacterial metabolic responses to antibiotics. The BONCAT approach can be applied to rapidly detect bacterial resistance to multiple antibiotics within 20 min of incubation, regardless of whether they act on proteins or DNA. In addition, the combination of BONCAT with the microscope enables the intuitive characterization of antibiotic-resistant bacteria in mixed systems at single-cell resolution. Furthermore, BONCAT coupled with flow cytometry exhibits good performance in determining bacterial resistance ratios to chloramphenicol and population heterogeneity in hospital wastewater samples. In addition, this approach is also effective in detecting antibiotic-resistant bacteria in natural water samples. Therefore, such a simple, fast, and efficient BONCAT-based approach will be valuable in monitoring the increase and spread of antibiotic resistance within natural and engineered aquatic environments.

Time-restricted feeding alleviates cardiac dysfunction induced by simulated microgravity via restoring cardiac FGF21 signaling.

Dietary restriction has been well-described to improve health metrics, but whether it could benefit pathophysiological adaptation to extreme environment, for example, microgravity, remains unknown. Here, we investigated the effects of a daily rhythm of fasting and feeding without reducing caloric intake on cardiac function and metabolism against simulated microgravity. Male rats under ad libitum feeding or time-restricted feeding (TRF; food access limited to 8 hours every day) were subjected to hindlimb unloading (HU) to simulate microgravity. HU for 6 weeks led to left ventricular dyssynchrony and declined cardiac function. HU also lowered pyruvate dehydrogenase (PDH) activity and impaired glucose utilization in the heart. All these were largely preserved by TRF. TRF showed no effects on HU-induced loss of cardiac mass, but significantly improved contractile function of cardiomyocytes. Interestingly, TRF raised liver-derived fibroblast growth factor 21 (FGF21) level and enhanced cardiac FGF21 signaling as manifested by upregulation of FGF receptor-1 (FGFR1) expression and its downstream markers in HU rats. In isolated cardiomyocytes, FGF21 treatment improved PDH activity and glucose utilization, consequently enhancing cell contractile function. Finally, both liver-specific knockdown (KD) of FGF21 and cardiac-specific FGFR1 KD abrogated the cardioprotective effects of TRF in HU rats. These data demonstrate that TRF improves cardiac glucose utilization and ameliorates cardiac dysfunction induced by simulated microgravity, at least partially, through restoring cardiac FGF21 signaling, suggesting TRF as a potential countermeasure for cardioprotection in long-term spaceflight.

Short-chain fatty acids exert opposite effects on the expression and function of p-glycoprotein and breast cancer resistance protein in rat intestine.

P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are involved in intestinal barrier. Short-chain fatty acids (SCFAs) play important roles in maintaining intestinal barrier. In this study we explored how SCFAs affected the expression and function of intestinal P-gp and BCRP in rats. Rats received 150 mM acetate, propionate or butyrate in drinking water for 4 weeks. In SCFA-treated rats, the expression and function of intestinal P-gp were decreased, but those of intestinal BCRP were increased; intestinal p-p65 was also decreased, which was positively related to P-gp protein expression. Among the three SCFAs tested, butyrate exhibited the strongest induction or inhibitory effect, followed by propionate and acetate. Similar results were observed in mouse primary enterocytes and Caco-2 cells treated with acetate (5 mM), propionate (2 mM), or butyrate (1 mM). In Caco-2 cells, addition of butyrate, vorinostat, and valproate (two classic HDAC inhibitors), Bay117082 (selective inhibitor of NF-κB activation) or NF-κB p65 silencing significantly decreased the expression of P-gp and the level of phosphorylated p65 (p-p65). Furthermore, butyrate attenuated the expression of P-gp and p-p65 induced by TNF-α (NF-κB activator) and theophylline (HDAC activator). However, vorinostat, valproate, Bay117082, TNF-α or p65 silencing hardly affected BCRP protein expression. But GW9662 (selective PPARγ antagonist) or PPARγ silencing abolished BCRP induction by butyrate and troglitazone (PPARγ agonist). SCFAs-treated rats showed higher intestinal protein expression of PPARγ, which was positively related to BCRP protein expression. Butyrate increased plasma exposure of fexofenadine but decreased that of rosuvastatin following oral dose to rats. In conclusion, SCFAs exert opposite effects on the expression and function of intestinal P-gp and BCRP; butyrate downregulated P-gp expression and function possibly via inhibiting HDAC/NF-κB pathways; butyrate induced BCRP expression and function partly via PPARγ activation.

Disulfiram-loaded lactoferrin nanoparticles for treating inflammatory diseases.

Sepsis is a dysregulated immune response to infection and potentially leads to life-threatening organ dysfunction, which is often seen in serious Covid-19 patients. Disulfiram (DSF), an old drug that has been used to treat alcohol addiction for decades, has recently been identified as a potent inhibitor of the gasdermin D (GSDMD)-induced pore formation that causes pyroptosis and inflammatory cytokine release. Therefore, DSF represents a promising therapeutic for the treatment of inflammatory disorders. Lactoferrin (LF) is a multifunctional glycoprotein with potent antibacterial and anti-inflammatory activities that acts by neutralizing circulating endotoxins and activating cellular responses. In addition, LF has been well exploited as a drug nanocarrier and targeting ligands. In this study, we developed a DSF-LF nanoparticulate system (DSF-LF NP) for combining the immunosuppressive activities of both DSF and LF. DSF-LF NPs could effectively block pyroptosis and inflammatory cytokine release from macrophages. Treatment with DSF-LF NPs showed remarkable therapeutic effects on lipopolysaccharide (LPS)-induced sepsis. In addition, this therapeutic strategy was also applied to treat ulcerative colitis (UC), and substantial treatment efficacy was achieved in a murine colitis model. The underlying mode of action of these DSF-LF-NPs may contribute to efficiently suppressing macrophage-mediated inflammatory responses and ameliorating the complications caused by sepsis and UC. As macrophage pyroptosis plays a pivotal role in inflammation, this safe and effective biomimetic nanomedicine may offer a versatile therapeutic strategy for treating various inflammatory diseases by repurposing DSF.

Age-related impairment of navigation and strategy in virtual star maze.

BACKGROUND: Although it is well known that aging impairs navigation performance, the underlying mechanisms remain largely unknown. Egocentric strategy requires navigators to remember a series of body-turns without relying on the relationship between environmental cues. Previous study suggested that the egocentric strategy, compared with non-egocentric strategy, was relatively unimpaired during aging. In this study, we aimed to examine strategy use during virtual navigation task and the underlying cognitive supporting mechanisms in older adults. METHODS: Thirty young adults and thirty-one older adults were recruited from the local community. This study adapted star maze paradigm using non-immersive virtual environment. Participants moved freely in a star maze with adequate landmarks, and were requested to find a fixed destination. After 9 learning trials, participants were probed in the same virtual star maze but with no salient landmarks. Participants were classified as egocentric or non-egocentric strategy group according to their response in the probe trial. RESULTS: The results revealed that older adults adopting egocentric strategy completed the navigation task as accurate as young adults, whereas older adults using non-egocentric strategy completed the navigation task with more detours and lower accuracy. The relatively well-maintained egocentric strategy in older adults was related to better visuo-spatial ability. CONCLUSIONS: Visuo-spatial ability might play an important role in navigation accuracy and navigation strategy of older adults. This study demonstrated the potential value of the virtual star maze in evaluating navigation strategy and visuo-spatial ability in older adults.

Physiologically based pharmacokinetic-pharmacodynamic modeling for prediction of vonoprazan pharmacokinetics and its inhibition on gastric acid secretion following intravenous/oral administration to rats, dogs and humans.

Vonoprazan is characterized as having a long-lasting antisecretory effect on gastric acid. In this study we developed a physiologically based pharmacokinetic (PBPK)-pharmacodynamic (PD) model linking to stomach to simultaneously predict vonoprazan pharmacokinetics and its antisecretory effects following administration to rats, dogs, and humans based on in vitro parameters. The vonoprazan disposition in the stomach was illustrated using a limited-membrane model. In vitro metabolic and transport parameters were derived from hepatic microsomes and Caco-2 cells, respectively. We found the most predicted plasma concentrations and pharmacokinetic parameters of vonoprazan in rats, dogs and humans were within twofold errors of the observed data. Free vonoprazan concentrations (fu × C2) in the stomach were simulated and linked to the antisecretory effects of the drug (I) (increases in pH or acid output) using the fomula dI/dt = k × fu × C2 × (Imax - I) - kd × I. The vonoprazan dissociation rate constant kd (0.00246 min-1) and inhibition index KI (35 nM) for H+/K+-ATPase were obtained from literatures. The vonoprazan-H+/K+-ATPase binding rate constant k was 0.07028 min-1· µM-1 using ratio of kd to KI. The predicted antisecretory effects were consistent with the observations following intravenous administration to rats (0.7 and 1.0 mg/kg), oral administration to dogs (0.3 and 1.0 mg/kg) and oral single dose or multidose to humans (20, 30, and 40 mg). Simulations showed that vonoprazan concentrations in stomach were 1000-fold higher than those in the plasma at 24 h following administration to human. Vonoprazan pharmacokinetics and its antisecretory effects may be predicted from in vitro data using the PBPK-PD model of the stomach. These findings may highlight 24-h antisecretory effects of vonoprazan in humans following single-dose or the sustained inhibition throughout each 24-h dosing interval during multidose administration.

Characterization and prognosis of estrogen receptor-positive/progesterone receptor-negative male breast cancer: a population-based study.

BACKGROUND: The aim of this study was to explore the characteristics and prognostic information of estrogen receptor-positive/progesterone receptor-negative (ER+/PR-) male breast cancer. METHODS: Using the US National Cancer Institute's Surveillance, Epidemiology, and End Results database, we compared the demographics, clinical characteristics, and outcome of estrogen receptor-positive/progesterone receptor-positive (ER+/PR+) patients with ER+/PR- male breast cancer patients from 1990 to 2010. Two thousand three hundred twenty-two patients with ER+/PR+ tumors and 355 patients with ER+/PR- tumors were included in our study. RESULTS: ER+/PR- patients were younger (P = 0.008) and more likely to be African American (P < 0.001) while presented with higher histological grade (P < 0.001), larger tumor size (P = 0.010), and more invasion to the lymph nodes (P = 0.034) and distant sites (P < 0.001), thus later stage (P = 0.001). Despite higher chance of receiving chemotherapy (51.0% vs 36.5%, P < 0.001), ER+/PR- patients experienced significantly worse breast cancer-specific survival (BSCC) (P < 0.001) and shorter overall survival (OS) (P = 0.003). Multivariate Cox model confirmed that tumor size, lymph node invasion, metastasis, and surgery were independent prognostic factors of both BSCC and OS for ER+/PR- male breast cancer. Age at diagnosis and chemotherapy were significantly associated with OS but not with BSCC. CONCLUSION: ER+/PR- male breast cancer was more aggressive and experienced shorter survival than ER+/PR+ patients. The prognosis was mainly associated with tumor size, lymph node invasion, metastasis, and surgery.

Fine regulation of ARF17 for anther development and pollen formation.

BACKGROUND: In Arabidopsis, the tapetum and microsporocytes are critical for pollen formation. Previous studies have shown that ARF17 is expressed in microsporocytes and tetrads and directly regulates tetrad wall synthesis for pollen formation. ARF17 is the direct target of miR160, and promoterARF17::5mARF17 (5mARF17/WT) transgenic plants, which have five silent mutations within the miR160-complementary domain, are sterile. RESULTS: Here, we found that ARF17 is also expressed in the tapetum, which was defective in arf17 mutants. Compared with arf17 mutants, 5mARF17/WT plants had abnormal tapetal cells and tetrads but were less vacuolated in the tapetum. Immunocytochemical assays showed that the ARF17 protein over-accumulated in tapetum, microsporocytes and tetrads of 5mARF17/WT plants at early anther stages, but its expression pattern was not affected during anther development. 5mARF17 driven by its native promoter did not rescue the arf17 male-sterile phenotype. The expression of 5mARF17 driven by the tapetum-specific promoter A9 led to a defective tapetum and male sterility in transgenic plants. These results suggest that the overexpression of ARF17 in the tapetum and microsporocytes of 5mARF17/WT plants leads to male sterility. Microarray data revealed that an abundance of genes involved in transcription and translation are ectopically expressed in 5mARF17/WT plants. CONCLUSIONS: Our work shows that ARF17 plays an essential role in anther development and pollen formation, and ARF17 expression under miR160 regulation is critical for its function during anther development.

Molecular Cloning, Recombinant Expression, and Funtional Characterization of APRIL (TNFSF13) in Cat (felis catus).

A proliferation-inducing ligand (APRIL) is a critical member of the tumor necrosis factor (TNF) superfamily, which is involved in immune regulation. In the present study, the cDNA of cat APRIL (cAPRIL) was successfully amplified. Sequence analysis showed that the open reading frame (ORF) of cAPRIL contains a putative furin protease cleavage site (R-R-K-R), a conserved putative N-glycosylation site (Asn(124)), and two conservative cysteine residues (Cys(196) and Cys(211)). Real-time quantitative PCR (qPCR) analysis revealed that cAPRIL could be detected in various tissues. The phylogenetic analysis and predicted three dimensional (3D) structure revealed that it is similar to its counterparts. The extracellular soluble domain of the cAPRIL (csAPRIL) fragment was cloned into the expression vector pET43.1a. SDS-PAGE and Western blotting analysis indicated a high-level expression of csAPRIL protein in Escherichia coli BL21 (DE3). MTT assays revealed that purified recombinant csAPRIL protein was able to stimulate proliferation of mouse B-cells. These findings indicate that cAPRIL plays an important role in proliferation of B-cells and provide the basis for investigation on the roles of APRIL in this important domestic species.

A highly selective chemosensor for Al(III) and Zn(II) and its coordination with metal ions.

This paper reports a fluorescence chemosensor, N-(benzimidazol-2-yl)salicylaldimine (H2L), for Zn(II) and Al(III) ions. H2L has high selectivity for Al(III) in dimethyl sulfoxide (DMSO) and for Zn(II) in N,N-dimethylformamide (DMF). In methanol, Zn(II) and Al(III) could also be distinguished by H2L with different excitation wavelengths. The fluorescent species [Zn(HL)(H2O)(CH3OH)](+), [Zn(HL)(H2O)(DMF)](+), [Al(HL)2(OH)(H2O)], and [Al(HL)(OH)2(H2O)(DMSO)] formed in solution were established by a combination of experimental and theoretical methods, including Job's plot, (1)H NMR titration, electrospray inonization mass spectrometry (ESI-MS), and B3LYP-SCRF/6-31(d) and TD-B3LYP-SCRF/6-31G* density functional theory methods. The results show that Zn(II) and Al(III) are all coordinated to the imine nitrogen atom and the hydroxyl oxygen atom from H2L, which is the same as the M(2+) ions in the obtained mononuclear complexes [M(HL)2(CH3OH)2] (where M = Cd, Ni, Co, and Mg). The detection limits of H2L for Zn(II) were 5.98 µM in methanol and 5.76 µM in DMF, while the detection limits of H2L for Al(III) were 3.3 µM in methanol and 5.25 µM in DMSO. Furthermore, it is also confirmed that H2L has low toxicity for HeLa cells and could be used to detect Zn(II) and Al(III) ions in living cells by bioimaging.

Silica nanoparticles inhibit cadmium uptake by the protozoan Tetrahymena thermophila without the need for adsorption.

The simultaneous presence of nanoparticles (NPs) and heavy metals in the environment may affect their mutual biological uptake. Although previous studies showed that NPs could alter the cellular uptake of heavy metals by their adsorption of heavy metals, whether they could affect metal uptake without the need for adsorption is unknown. This study examined the effects of silica (SiO2) NPs on the uptake of Cd ion by the protozoan Tetrahymena thermophila. We found that, even with negligible levels of adsorption, SiO2 NPs at concentrations of 3 to 100 mg/L inhibited Cd uptake. This inhibitory effect decreased as the ambient Cd concentration increased from 1 to 100 µg/L, suggesting the involvement of at least two transporters with different affinities for Cd. The transporters were subsequently identified by the specific protein inhibitors amiloride and tariquidar as NCX and ABCB1, which are responsible for the uptake of Cd at low and high Cd levels, respectively. RT-qPCR and molecular dynamics simulation further showed that the inhibitory effects of SiO2 NPs were attributable to the down-regulated expression of the genes Ncx and Abcb1, steric hindrance of Cd uptake by NCX and ABCB1, and the shrinkage of the central channel pore of the transporters in the presence of SiO2 NPs. SiO2 NPs more strongly inhibited Cd transport by NCX than by ABCB1, due to the higher binding affinity of SiO2 NPs with NCX. Overall, our study sheds new light on a previously overlooked influence of NPs on metal uptake and the responsible mechanism.

Association between delayed initiation of adjuvant CMF or anthracycline-based chemotherapy and survival in breast cancer: a systematic review and meta-analysis.

BACKGROUND: Adjuvant chemotherapy (AC) improves survival among patients with operable breast cancer. However, the effect of delay in AC initiation on survival is unclear. We performed a systematic review and meta-analysis to determine the relationship between time to AC and survival outcomes. METHODS: PubMed, EMBASE, Cochrane Database of Systematic Reviews, and Web-of-Science databases (between January-1 1978 and January-29, 2013) were searched for eligible studies. Hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) from each study were converted to a regression coefficient (ß) corresponding to a continuous representation per 4-week delay of AC. Most used regimens of chemotherapy in included studies were CMF (cyclophosphamide, methotrexate, and fluorouracil) or anthracycline-based. Individual adjusted ß were combined using a fixed-effects or random-effects model depending on heterogeneity. RESULTS: We included 7 eligible studies with 9 independent analytical groups involving 34,097 patients, 1 prospective observational study, 2 secondary analyses in randomized trials (4 analytical groups), and 4 hospital-/population-based retrospective study. The overall meta-analysis demonstrated that a 4-week increase in time to AC was associated with a significant decrease in both OS (HR = 1.15; 95% confidence interval [CI], 1.03-1.28; random-effects model) and DFS (HR = 1.16; 95% CI, 1.01-1.33; fixed-effects model). One study caused a significant between-study heterogeneity for OS (P < 0.001; I² = 75.4%); after excluding that single study, there was no heterogeneity (P = 0.257; I² = 23.6%) and the HR was more significant (HR = 1.17; 95% CI, 1.12-1.22; fixed-effects model). Each single study did not fundamentally influence the positive outcome and no evidence of publication bias was observed in OS. CONCLUSIONS: Longer time to AC is probably associated with worse survival in breast cancer patients.

Highly efficient α-C-sialylation promoted by (p-Tol)2SO/Tf2O with N-acetyl-5-N,4-O-oxazolidione protected thiosialoside as donor.

Based on a preactivation protocol with (p-Tol)2SO/Tf2O, a practical, straightforward, and high-yielding synthesis of α-sialyl C-glycosides was accomplished by coupling N-acetyl-5-N,4-O-oxazolidione protected thiosialoside with various trimethylsilyl enol ethers and allyltrimethylsilanes. High yields and excellent α-selectivities were obtained for the strong π-nucleophiles with large nucleophilicity values (N = 4.4-9.0), irrespective of whether silyl enol ethers, silyl ketene acetals or allyltrimethylsilanes were used for the electrophilic C-sialylation.

Effects of exergame and bicycle exercise intervention on blood pressure and executive function in older adults with hypertension: A three-group randomized controlled study.

Management of hypertension and prevention of cognitive decline are challenging public health problems. However, the effects of exergame intervention on blood pressure (BP) remain to be explored, and whether exergame intervention is an effective alternative to traditional physical exercise intervention for older adults with hypertension remains to be demonstrated. This study aimed to explore the effectiveness of moderate-intensity exergame intervention and bicycle exercise training on BP and executive function in older hypertensive patients. A total of 128 participants were randomly assigned to the exergame intervention group (n = 41), bicycle exercise intervention group (n = 44), and control group (n = 43). The intervention groups exercised for 60 min, 3 times per week, for 16 weeks, while the control group maintained their normal lifestyle. The results revealed that there were no significant differences between two intervention groups and control group in systolic BP and diastolic BP changes (ps > 0.05). Both intervention groups demonstrated significant improvements in working memory when compared with control group (exergame intervention group: -461.9 ms, p = 0.025; bicycle exercise intervention group: -470.1 ms, p = 0.021). There were no significant differences in systolic BP, diastolic BP, or working memory between the two intervention groups after 16 weeks of training (ps > 0.05). No difference in inhibition or cognitive flexibility was observed between the intervention and control groups (ps > 0.05). The current results showed that moderate-intensity exergame intervention did not produce significant benefits in reducing BP, but yielded similar beneficial effects in working memory to that of bicycle exercise intervention. More studies are needed on whether exergame intervention has the potential to be a promising supplemental therapeutic tool for older adults with hypertension.

Detection of Burkholderia pseudomallei with CRISPR-Cas12a based on specific sequence tags.

Melioidosis is a bacterial infection caused by Burkholderia pseudomallei (B. pseudomallei), posing a significant threat to public health. Rapid and accurate detection of B. pseudomallei is crucial for preventing and controlling melioidosis. However, identifying B. pseudomallei is challenging due to its high similarity to other species in the same genus. To address this issue, this study proposed a dual-target method that can specifically identify B. pseudomallei in less than 40 min. We analyzed 1722 B. pseudomallei genomes to construct large-scale pan-genomes and selected specific sequence tags in their core genomes that effectively distinguish B. pseudomallei from its closely related species. Specifically, we selected two specific tags, LC1 and LC2, which we combined with the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated proteins (Cas12a) system and recombinase polymerase amplification (RPA) pre-amplification. Our analysis showed that the dual-target RPA-CRISPR/Cas12a assay has a sensitivity of approximately 0.2 copies/reaction and 10 fg genomic DNA for LC1, and 2 copies/reaction and 20 fg genomic DNA for LC2. Additionally, our method can accurately and rapidly detect B. pseudomallei in human blood and moist soil samples using the specific sequence tags mentioned above. In conclusion, the dual-target RPA-CRISPR/Cas12a method is a valuable tool for the rapid and accurate identification of B. pseudomallei in clinical and environmental samples, aiding in the prevention and control of melioidosis.

Identification of potential pathogenic targets and survival strategies of Vibrio vulnificus through population genomics.

Vibrio vulnificus, a foodborne pathogen, has a high mortality rate. Despite its relevance to public health, the identification of virulence genes associated with the pathogenicity of currently known clinical isolates of V. vulnificus is incomplete and its synergistic pathogenesis remains unclear. Here, we integrate whole genome sequencing (WGS), genome-wide association studies (GWAS), and genome-wide epistasis studies (GWES), along with phenotype characterization to investigate the pathogenesis and survival strategies of V. vulnificus. GWAS and GWES identified a total of six genes (purH, gmr, yiaV, dsbD, ramA, and wbpA) associated with the pathogenicity of clinical isolates related to nucleotide/amino acid transport and metabolism, cell membrane biogenesis, signal transduction mechanisms, and protein turnover. Of these, five were newly discovered potential specific virulence genes of V. vulnificus in this study. Furthermore, GWES combined with phenotype experiments indicated that V. vulnificus isolates were clustered into two ecological groups (EGs) that shared distinct biotic and abiotic factors, and ecological strategies. Our study reveals pathogenic mechanisms and their evolution in V. vulnificus to provide a solid foundation for designing new vaccines and therapeutic targets.