Ameliorative Effect of Natural Sesquiterpene Alcohol Cedrol Against Cerebral Ischemia Infarction-In Vitro and In Vivo Studies.

Cedrol is a major bioactive compound present in the Cedrus atlantica with numerous biological properties. In this study, we elucidated the neuroprotective properties of cedrol against ischemic infarction in animal and in vitro studies. A cerebral ischemic/reperfusion model was induced in adult Wistar rats, and oxygen-glucose deprivation/reperfusion was induced in SH-SY5Y neuronal cells and treated with different concentrations of cedrol. The percentage of water content, cerebral  infarct, and neurological deficit score was assessed in experimental rats. The acetylcholinesterase activity and inflammatory cytokines were quantified to analyze the anti-inflammatory potency of cedrol. Oxidative stress marker malondialdehyde and antioxidants were quantified to evaluate the antioxidant potency of cedrol in an ischemic condition. The neuroprotective potency of cedrol was confirmed by histopathological analysis of the brain tissue of cedrol-treated I/R-induced rats. In in vitro studies, the MTT and LDH assays were performed in cedrol-treated OGD/R SH-SY5Y cells to analyze the cytoprotective effect of cedrol. The anti-inflammatory property of cedrol was confirmed by quantifying the pro-inflammatory cytokine levels in OGD/R-induced cedrol-treated SH-SY5Y cells. The results obtained prove that cedrol significantly prevents brain edema, neurological deficits, acetylcholinesterase activity, and oxidative damage in ischemic-induced rats. It inhibited neuroinflammation in ischemic-induced rats and also in in vitro models. The neuroprotective effect of cedrol during an ischemic condition was authentically established with histological analysis in an animal model and cell survival assays in an in vitro model. Overall, our results confirm that cedrol is a potent alternative drug to treat cerebral ischemia in the future.

Schiff base functionalized dialdehyde starch for enhanced removal of Cu (II): Preparation, performances, DFT calculations.

Dialdehyde starch modified by 2-hydrazinopyridine (HYD-DAS) based on the reaction of dialdehyde starch (DAS) and 2-hydrazinopyridine was synthesized and characterized by FT-IR spectra, element analysis and SEM. HYD-DAS can efficiently adsorb Cu (II) ion to demonstrate visual color changes from yellow to dark brown in aqueous solutions. The influence on HYD-DAS to Cu (II) adsorption including pH value of solution, isotherm, kinetics, thermodynamics and possible mechanism had also been examined. Batch experiments indicate that HYD-DAS's to Cu (II) adsorption reaches equilibrium within 250 min, and its adsorption capacity and rate are 195.75 mg/g and 98.63 %, respectively. Moreover, HYD-DAS to Cu (II) adsorption remains robust and underscoring after five cycles to exhibit good selectivity and reusability. Kinetics studies suggest the absorption process follows a quasi-second-order with isotherms aligning to the Langmuir monolayer model, and thermodynamics reveals that it is a spontaneous endothermic nature of adsorption. Based on the analyses of XPS and DFT calculations, a possible mechanism for HYD-DAS to Cu (II) adsorption is that Cu (II) combined with nitrogen atoms from Schiff base and hydrazine pyridine ring in HYD-DAS.

MS/MS-based molecular networking discovery of sesquiterpenes from Carpesium abrotanoides L. with their cytotoxic and acetylcholinesterase inhibitory activity.

Employing an MS/MS-based molecular networking-guided strategy, three new eudesmane-type sesquiterpenes (1-3) and one undescribed pseudoguaianolide sesquiterpene (8), along with four known eudesmane-type sesquiterpene lactones (4-7) were extracted and purified from the herbs of Carpesium abrotanoides L. Structural elucidation encompassed comprehensive spectroscopic analysis, NMR calculations, DP4+ analysis, and ECD calculations. The cytotoxicity activity of all isolates was evaluated against two human hepatoma carcinoma cells (HepG2 and Hep3B) in vitro. It was demonstrated that compounds 2 and 4 showed moderate cytotoxic against HepG2 and Hep3B cells. Furthermore, all compounds were evaluated for their acetylcholinesterase (AChE) inhibitory activity. Particularly noteworthy is that, in comparison to the positive control, compound 1 demonstrated significant AChE inhibition with an inhibition rate of 77.86%. In addition, the inhibitory mechanism of compound 1 were investigated by in silico docking analyze and molecular dynamic simulation.

Regulating Effect of Exogenous α-Ketoglutarate on Ammonium Assimilation in Poplar.

Extensive industrial activities and anthropogenic agricultural practices have led to substantial ammonia release to the environment. Although croplands can act as ammonia sinks, reduced crop production under high concentrations of ammonium has been documented. Alpha-ketoglutarate (AKG) is a critical carbon source, displaying pleiotropic physiological functions. The objective of the present study is to disclose the potential of AKG to enhance ammonium assimilation in poplars. It showed that AKG application substantially boosted the height, biomass, and photosynthesis activity of poplars exposed to excessive ammonium. AKG also enhanced the activities of key enzymes involved in nitrogen assimilation: glutamine synthetase (GS) and glutamate synthase (GOGAT), elevating the content of amino acids, sucrose, and the tricarboxylic acid cycle (TCA) metabolites. Furthermore, AKG positively modulated key genes tied to glucose metabolism and ATP synthesis, while suppressing ATP-depleting genes. Correspondingly, both H+-ATPase activity and ATP content increased. These findings demonstrate that exogenously applying AKG improves poplar growth under a high level of ammonium treatment. AKG might function through sufficient carbon investment, which enhances the carbon-nitrogen balance and energy stability in poplars, promoting ammonium assimilation at high doses of ammonium. Our study provides novel insight into AKG's role in improving poplar growth in response to excess ammonia exposure.

Value of the Air Bronchogram Sign and Other Computed Tomography Findings in the Early Diagnosis of Lung Adenocarcinoma.

OBJECTIVES: The present study aims to explore the application value of the air bronchogram (AB) sign and other computed tomography (CT) signs in the early diagnosis of lung adenocarcinoma (LUAD). METHOD: The pathological information and CT images of 130 patients diagnosed with N0 and M0 solitary pulmonary nodules (diameter ≤3 cm) and treated with surgical resection in our hospital between June 2021 and June 2022 were analyzed. RESULTS: The patients were divided into the benign pulmonary nodule (BPN) group (14 cases), the AIS group (30 cases), the MIA group (10 cases), and the IAC group (76 cases). Among the 116 patients with AIS and LUAD, 96 showed an AB sign. Among the 14 patients with BPN, only 4 patients showed an AB sign. The average CT value and maximum diameter were significantly higher in the IAC group than in the AIS and MIA groups. In the BPN group, 5 patients had an average CT value of >80 HU. Among all LUAD-based groups, there was only 1 patient with a CT value of >60 HU. CONCLUSIONS: The identification of the AB sign based on CT imaging facilitates the differentiation between benign and malignant nodules. The CT value and maximum diameter of pulmonary adenocarcinoma nodules increase with the increase of the malignancy degree. The nodule type, CT value, and maximum diameter are useful for predicting the pathological type and prognosis. If the average CT value of pulmonary nodules is >80 HU, LUAD may be excluded.

Analysis of inappropriate prophylactic use of proton pump inhibitors during the perioperative period: an observational study.

BACKGROUND: The prevalence and characteristics of inappropriate use of proton pump inhibitors (PPIs) to prevent stress-related mucosal disease (SRMD) during the perioperative period and its associated factors are rarely reported. This study aimed to investigate the prevalence and characteristics of inappropriate prophylactic use of proton pump inhibitors (PPIs) during the perioperative period and identify its associated factors in a tertiary care and academic teaching hospital in China and to provide evidence for regulation authorities and pharmacists to take targeted measures to promote rational drug use. METHODS: Inpatients who underwent surgical operations and received prophylactic use of PPIs from June 2022 to November 2022 were included in this retrospective study. The appropriateness of perioperative prophylactic use of PPIs was evaluated by clinical pharmacists. Associated factors with inappropriate perioperative prophylactic use of PPIs were analyzed by univariable and multivariable logistic regression. RESULTS: Four-hundred seventy-two patients were finally included in this study, of which 131 (27.75%) patients had at least one problem with inappropriate perioperative prophylactic use of PPIs. The three most common problems were drug use without indication (52.0%), inappropriate usage and dosage (34.6%), and inappropriate duration of medication (6.7%). Multiple logistic regression analysis showed that oral dosage form of PPIs [OR = 18.301, 95% CI (7.497, 44.671), p < 0.001], discharge medication of PPIs [OR = 11.739, 95% CI (1.289, 106.886), p = 0.029], and junior doctors [OR = 9.167, 95% CI (3.459, 24.299), p < 0.001] were associated with more inappropriate prophylactic use of PPIs. Antithrombotics [OR = 0.313, 95% CI (0.136, 0.721), p = 0.006] and prolonged postoperative hospital stay (longer than 15 days) [OR = 0.262, 95% CI (0.072, 0.951), p = 0.042] were associated with less inappropriate prophylactic use of PPIs. CONCLUSIONS: The inappropriate prophylactic use of PPIs during the perioperative period is common. Regulation authorities and pharmacists should take more targeted measures to promote the rational prophylactic use of PPIs during the perioperative period.

Integrative omics studies revealed synergistic link between sucrose metabolic isogenes and carbohydrates in poplar roots infected by Fusarium wilt.

Advances in carbohydrate metabolism prompted its essential role in defense priming and sweet immunity during plant-pathogen interactions. Nevertheless, upstream responding enzymes in the sucrose metabolic pathway and associated carbohydrate derivatives underlying fungal pathogen challenges remain to be deciphered in Populus, a model tree species. In silico deduction of genomic features, including phylogenies, exon/intron distributions, cis-regulatory elements, and chromosomal localization, identified 59 enzyme genes (11 families) in the Populus genome. Spatiotemporal expression of the transcriptome and the quantitative real-time PCR revealed a minuscule number of isogenes that were predominantly expressed in roots. Upon the pathogenic Fusarium solani (Fs) exposure, dynamic changes in the transcriptomics atlas and experimental evaluation verified Susy (PtSusy2 and 3), CWI (PtCWI3), VI (PtVI2), HK (PtHK6), FK (PtFK6), and UGPase (PtUGP2) families, displaying promotions in their expressions at 48 and 72 h of post-inoculation (hpi). Using the gas chromatography-mass spectrometry (GC-MS)-based non-targeted metabolomics combined with a high-performance ion chromatography system (HPICS), approximately 307 metabolites (13 categories) were annotated that led to the quantification of 46 carbohydrates, showing marked changes between three compared groups. By contrast, some sugars (e.g., sorbitol, L-arabitol, trehalose, and galacturonic acid) exhibited a higher accumulation at 72 hpi than 0 hpi, while levels of α-lactose and glucose decreased, facilitating them as potential signaling molecules. The systematic overview of multi-omics approaches to dissect the effects of Fs infection provides theoretical cues for understanding defense immunity depending on fine-tuned Suc metabolic gene clusters and synergistically linked carbohydrate pools in trees.

Identification of priority areas for territorial space ecological restoration in arid area of Northwest China: A case study of Zhangye City in Heihe River basin.

Determining priority areas for territorial ecological restoration in the arid region of Northwest China based on the holistic protection and systematic governance is an important measure to build solid national ecological security barrier and promote the construction of territorial ecological civilization. Taking Zhangye City, a typical arid area city in Northwest China, as an example, we constructed the research framework of "ecological network-ecological sensitivities-ecological degradation" from two aspects of internal defects and external threats of ecological networks by using circuit theory and assessment methods of ecological service function importance, ecological sensitivity, and ecological degradation. We then identified the priority areas of territorial ecological restoration in northwest arid region and put forward the restoration strategies. The results showed that the priority areas of ecological restoration in Zhangye City were concentrated in the artificial shelterbelt along rivers and the plain-desert-oasis transition zone with fragile ecology and strong human interference. The ecological network of the study area included 39 ecological sources and 99 ecological corridors, and the highly sensitive and degraded areas were 1595.40 and 6.65 km2. Based on the internal defects and external threats of the ecological network, we identified 31 ecological pinch points, 7 obstacle points, and 753.56 km2 ecological source areas in the territorial spatial ecological restoration priority area. These areas were related to the connectivity of the ecological network internally and the stability maintenance of the ecosystem outwards, and were the areas to restoration in the future. Following the concept of overall protection and system restoration of territorial space, we put forward the idea of territorial space restoration by integrating internal defects and external threats of ecological network, which could provide scientific decision-making basis for comprehensive ecosystem management and territorial optimization of Zhangye City.

Association between serum ferritin and bone turnover marker levels in type 2 diabetes mellitus patients with non-alcoholic fatty liver disease.

OBJECTIVE: To investigate the correlation between serum ferritin (SF) and bone turnover markers in type 2 diabetes mellitus (T2DM) patients with non-alcoholic fatty liver disease (NAFLD). METHODS: Seven hundred and forty-two people with T2DM were selected. Serum bone turnover markers: osteocalcin (OC), type I procollagen N-terminal peptide (PINP), ß-I type collagen carboxy-terminal peptide (ß-CTx), and 25-hydroxyvitamin D3 (25-[OH]-D) levels were detected. High SF (HF) was defined as the indicated SF levels above 400 ng/mL in males and more than 150 ng/mL in females. Patients were divided into four groups: T2DM+normal SF (non-HF); T2DM+high SF (HF); T2DM+NAFLD+non-HF; andT2DM+NAFLD+HF. Relationships between SF and bone turnover markers were analyzed. RESULTS: Compared with the T2DM+non-HF group, ß-CTx levels were higher in the T2DM+HFgroup. Compared with the T2DM+NAFLD+non-HF group, ß-CTx levels were increased and 25-(OH)-D levels decreased in the T2DM+NAFLD+HF group (all p < 0.05). SF was positively correlated with ß-CTx [ß = 0.074; 95% CI (0.003, 0.205)] and negatively correlated with 25-(OH)-D [ß=-0.108; 95%CI (-0.006, -0.001)]. Compared with the T2DM+non-HF group, an independent positive correlation was found between ß-CTx and SF in the T2DM+NAFLD+HF group [OR = 1.002; 95% CI (1.001, 1.004)]. Among males, SF was positively correlatedwith ß-CTx [ß = 0.114; 95% CI (0.031, 0.266)]. SF was negatively correlated with 25-(OH)-D levels in both male and female patients [ß=-0.124; 95% CI (0.007,0.001) and ß=-0.168; 95% CI (-0.012, -0.002)]. Among those >50 years of age and postmenopausal females, SF was negatively correlated with 25-(OH)-D levels [ß=-0.117; 95% CI (-0.007, -0.001) and ß=-0.003; 95% CI (-0.013, -0.003)]. CONCLUSION: SF level was positively correlated with ß-CTx in T2DM patients with NAFLD, which may promote bone resorption and increase the risk of bone loss.

Association of serum uric acid with all-cause and cardiovascular mortality in chronic kidney disease stages 3-5.

BACKGROUND AND AIMS: The role of serum uric acid (SUA) in the prognosis of chronic kidney disease (CKD) is inconclusive. To explore the association of SUA level with all-cause and cardiovascular disease (CVD) mortality in patients with CKD. METHODS AND RESULTS: Leveraging data from the National Health and Nutritional Examination Survey (NHANES) and linked national death records up to December 31 2019, we explored the association of SUA with all-cause and CVD mortality using weighted cox proportional hazards regression models and restricted cubic spline (RCS) models in patients with CKD stages 3-5. The study finally included 2644 patients with CKD stages 3-5, with a median SUA level of 6.5 mg/dL. After a median follow-up of 55 months, a total of 763 deaths were recorded, with 279 of them attributed to CVD. In the fully adjusted model, per 1 mg/dL increment in SUA concentration was found to be associated with increased HRs (95% CIs) of 1.07 (1.00, 1.14) for all-cause mortality and 1.11 (1.00, 1.24) for CVD mortality. Compared to Q2 (reference), those in Q4 had adjusted HRs of 1.72 (1.36, 2.17) for all-cause mortality and 2.17 (1.38, 3.41) for CVD mortality, while those in Q1 had adjusted HRs of 1.49 (1.19, 1.85) for all-cause mortality and 1.93 (1.26, 2.98) for CVD mortality. CONCLUSIONS: Both higher and lower SUA levels were associated with increased risks of all-cause and CVD mortality in patients with CKD stages 3-5.

CO-Assisted Methane Oxidation into Oxygenates over Surface Platinum-Titanium Alloyed Layers.

Methane oxidation using molecular oxygen remains a grand challenge in which the obstacle is not only the activation of methane but also the reaction with oxygen, considering the mismatch of the ground spin states. Herein, we report TiO2-supported Pt nanocrystals (Pt/TiO2) with surface Pt-Ti alloyed layers that directly convert methane into oxygenates by using O2 as the oxidant with the assistance of CO. The oxygenate yield reached 749.8 mmol gPt-1 in a H2O aqueous solution over 0.1% Pt/TiO2 under 31 bar of mixed gas (20:5:6 CH4:CO:O2) at 150 °C for 3 h, while the CH3OH selectivity was 62.3%. On the basis of the control experiments and spectroscopic results, we identified the surface Pt-Ti alloy as the active sites. Moreover, CO promoted the dissociation of O2 on the surface of Pt-Ti alloyed layers and the subsequent activation of CH4 to form oxygenated products.

Constructing Dynamic Anode/Electrolyte Interfaces Coupled with Regulated Solvation Structures for Long-Term and Highly Reversible Zinc Metal Anodes.

Aqueous zinc ion batteries (AZIBs) show a great potential for next-generation energy storage due to their high safety and high energy density. However, the severe side reactions of zinc negative electrode largely hinder the further application of AZIBs. Herein, trace tris(hydroxymethyl)aminomethane (Tris) additive with rich lone-pair-electrons and zincophilic sites is firstly introduced to achieve long-term and highly reversible Zn plating/stripping. Specifically, Tris not only regulates the solvation structure of Zn2+, but is also adsorbed vertically on the Zn anode surface with a changed coordination intensity during the plating/stripping process of Zn to generate an in situ dynamic adsorption layer for the first time. The dynamic adsorption layer could successively attract the solvated Zn2+ and then promote the de-solvation of the solvated Zn2+ owing to the orientation polarization with regularly-changed applied electric field, the volume rejection effect, and strong intermolecular force towards H2O of the vertically-adsorbed Tris. Therefore, an improved Zn2+-transport kinetics as well as the inhibition of side reactions of Zn anode are successfully realized. Accordingly, the Zn||Zn symmetric cell provides an ultra-long cycle life of 2600 h. Furthermore, the Zn||MnO2 full cell with Tris could demonstrate a high capacity and structural stability for practical applications.

Lysyl Oxidase Promotes the Formation of Vasculogenic Mimicry in Gastric Cancer through PDGF-PDGFR Pathway.

Objective: Vasculogenic mimicry (VM) generates an important supplementary form of blood supply in cancer, which many factors regulate. However, the effect of lysyl oxidase (LOX) on VM formation is unclear. In this study, gastric cancer tissues and cells were used to investigate the role of LOX in the formation of VM. Materials and Methods: The samples were collected from 49 patients with a final diagnosis of gastric cancer. According to metastasis (including lymph node metastases and distant metastases), gastric cancer samples were divided into metastasis and non-metastasis groups. Based on the degree of invasion, gastric cancer specimens were divided into T1 + T2 and T3 + T4 groups. The relative expression of LOX was detected using Western blot. The formation of VM was measured by double staining with CD34 and Periodic acid-Schiff (PAS) in gastric cancer tissue slices, and the correlation between LOX and VM was analyzed with Pearson's correlation analysis. Gastric cancer cell line BGC-803 was treated with LOX, ß-aminopropionitrile (BAPN, an inhibitor of LOX), and AG1295 or AG1296 (inhibitors of the platelet-derived growth factor receptor). The formation of VM was then measured using PAS staining. The expression of platelet-derived growth factor receptor (PDGFR)α and PDGFRß in gastric cancer cells was detected by Western blot. Results: In gastric cancer samples, the level of LOX was higher in the metastasis group than in the non-metastasis group (P < 0.05) and in the T3 + T4 group than in the T1 + T2 group (P < 0.05). VM formation was greater in the T3+T4 group than in the T1+T2 group (P < 0.05) and in the metastasis group than in the non-metastasis group (P < 0.05). The expression level of LOX was positively correlated with VM formation (P < 0.01). In gastric cancer cells, LOX concentration was positively correlated with the degree of VM, and BAPN concentration was negatively correlated with the degree of VM (P <0.05). PDGFR levels in the T3+T4 and metastasis groups were relatively higher (P <0.01) and positively correlated with LOX levels in gastric cancer specimens (P < 0.01). The relative expression of PDGFRα and PDGFRß in gastric cancer cells was up-regulated with increasing LOX and downregulated with increasing BAPN (P < 0.05). With inhibition of PDGFRα and PDGFRß using AG1295 or AG1296, VM formation in gastric cancer cells decreased (P <0.05), but the number of VM structures increased while LOX was added (P < 0.05). Conclusion: LOX partially promotes the formation of VM in gastric cancer through the PDGF-PDGFR signaling pathway.

Target isolation of diverse sesquiterpenoid from the stems of Daphne genkwa based on molecular networking.

Guiding by LC-MS/MS analysis and the Global Natural Products Social (GNPS) Molecular Networking, three undescribed sesquiterpenoids, stedapgens A-C, and two known analogues were discovered in the barks of Daphne genkwa Sieb. et Zucc. The structures were determined by analysis of their spectroscopic data and quantum-chemical calculations. All the isolated novel compounds were tested for their acetylcholinesterase inhibitory activities with IC50 = 0.754 ± 0.059, 0.696 ± 0.026, and 0.337 ± 0.023 µg/ml. Among them, stedapgen A displayed promising inhibitory activities against AChE, and the binding sites were predicted by molecular docking.

In vitro and in vivo genome-based safety evaluation of Lacticaseibacillus rhamnosus LRa05.

The aim of this study was to comprehensively evaluate the safety of Lacticaseibacillus rhamnosus LRa05 (hereinafter "LRa05") to determine its suitability for use as a probiotic in the food industry. First, we sequenced the genome of LRa05 and then determined whether it contained genes associated with antibiotic resistance, virulence, or pathogenicity. Second, we evaluated the safety of LRa05 in vitro by performing a hemolysis assay and examining its ability to produce biogenic amines, its antimicrobial susceptibility, its capacity to transfer antibiotic resistance genes, its genomic stability, and whether it contained potential virulence factors. Third, we investigated the pathogenicity of LRa05 in mice by oral gavage and intraperitoneal injection. A bioinformatics analysis revealed no evidence that the genome of LRa05 contains genes associated with virulence or antibiotic resistance. In addition, the results of in vitro experiments showed that LRa05 does not produce d-lactic acid or exhibit hemolytic activity and is sensitive to clinically relevant antibiotics. Furthermore, a pathogenicity test revealed that LRa05 exhibits no lethality or toxicity in mice. Taken together, these findings indicate that LRa05 is sufficiently safe to be explored as a potential probiotic for use in the food industry.

Evolution of fermented grain yeast communities in strong-flavored baijiu and functional validation of yeasts that produce superior-flavored substances.

BACKGROUND: Baijiu is a well-known alcoholic beverage in China and the quality is determined by various microorganisms during the fermentation process. Yeast is one of the most important microorganisms in the fermentation of baijiu. It has a strong esterification capacity and also affects the aroma. RESULTS: High-throughput sequencing results showed that the fermented grains (jiupei) during baijiu production were mainly composed of eight highly abundant yeast species. The species and abundance of yeasts changed significantly with the fermentation process. The flavor of 30 yeast strains in the jiupei was determined by a sniffing test and gas chromatography-mass spectrometry (GC-MS). The strain with the highest flavor substance content (2.34 mg L-1 ), named YX3205, was identified as Clavispora lusitaniae. Tolerance results showed that C. lusitaniae YX3205 can tolerate up to 15% (v v-1 ) ethanol. In a solid-state simulated fermentation experiment, the content of 24 flavor substances was significantly increased in the fortified group, and the total ester content reached 4240.73 µg kg-1 , which was 2.8 times higher than that of the control group. CONCLUSION: The present study demonstrated the potential of C. lusitaniae YX3205 to enhance the flavor of baijiu, thereby serving as a valuable strain for the improvement of the flavor quality of baijiu. © 2024 Society of Chemical Industry.

Transcriptomic interplay between Acinetobacter baumannii , human macrophage and polymyxin.

Optimization of antibiotic therapy has been hindered by our dearth of understanding on the mechanism of the host-pathogen-drug interactions. Here, we employed dual RNA-sequencing to examine transcriptomic perturbations in response to polymyxin B in a co-culture infection model of Acinetobacter baumannii and human macrophages. Our findings revealed that polymyxin B treatment induced significant transcriptomic response in macrophage-interacting A. baumannii , exacerbating bacterial oxidative stress, disrupting metal homeostasis, affecting osmoadaptation, triggering stringent stress response, and influencing pathogenic factors. Moreover, infected macrophages adapt heme catabolism, coagulation cascade, and hypoxia-inducible signaling to confront bacterial invasion. Disrupting rcnB , ompW , and traR/dksA genes in A. baumannii impairs metal homeostasis, osmotic stress defense and stringent responses, thereby enhancing antibacterial killing by polymyxin. These findings shed light on the global stress adaptations at the network level during host-pathogen-drug interactions, revealing promising therapeutic targets for further investigation. IMPORTANCE: In the context of the development of bacterial resistance during the course of antibiotic therapy, the role of macrophages in shaping bacterial response to antibiotic killing remains enigmatic. Herein we employed dual RNA-sequencing and an in vitro tripartite model to delve into the unexplored transcriptional networks of the Acinetobacter baumannii -macrophage-polymyxin axis. Our findings uncovered the potential synergy between macrophages and polymyxin B which appear to act in co-operation to disrupt multiple stress tolerance mechanisms in A. baumannii . Notably, we discovered the critical roles of bacterial nickel/cobalt homeostasis ( rcnB family), osmotic stress defense ( ompW family), and stringent response regulator ( traR/dksA C4-type zinc finger) in tolerating the last-line antibiotic polymyxin B. Our findings may lead to potential targets for the development of novel therapeutics against the problematic pathogen A. baumannii .

Immune profiles to predict bortezomib-based treatment response for multiple myeloma patients.

BACKGROUND: To evaluate the distribution of bone marrow immune cell subsets and their correlation with treatment efficacy in patients with multiple myeloma (MM). METHODS: We analyzed the bone marrow lymphocyte subsets of 186 newly diagnosed MM patients at diagnosis and their correlation with clinical characteristics. In our study, eight-color flow cytometry, a method commonly used to detect plasma cell phenotypes, was used to analyze seven bone marrow immune cell groups by change gate-strategy. RESULTS: First, for all the 7 immune cell groups, the percentage of immature B cells was significantly lower in stage III patients than in stage I patients, while the trend was reversed in memory B cells in both the International Staging System(p = 0.004) and Revised International Staging System(p = 0.018). Second, the percentage of naïve B cells were significantly lower in patients with severe anemia, while the percentage of memory B cells had reversed trend. The percentage of immature B cells were lower in patients with Cr ≥ 2 mg/dL than in patients with Cr < 2 mg/dL. Then we followed the treatment efficacy of 152 patients who received four cycles of induction therapy (bortezomib + dexamethasone or bortezomib + lenalidomide + dexamethasone) and analyzed the relationship between bone marrow lymphocyte subsets at the initial stage and treatment response datasets. We found that both the percentage of B cells(p＜0.001) and immature B(p = 0.002) were increased in patients who achieved very good partial remission(VGPR) after four cycles of induction therapy. The ROC results indicated the combination of the multiple immune subgroups had predictive values (AUC = 0.802, p<0.001) in the treatment effect after four cycles of induction therapy. CONCLUSIONS: Overall, these results suggest that the analysis of lymphocyte subsets along with plasma cell immunophenotyping could be a potential index for determining the prognosis of MM patients.