Insight into the Role of NH3/NH4+ and NOx/NO3- in the Formation of Nitrogen-Containing Brown Carbon in Chinese Megacities.

Particulate brown carbon (BrC) plays a crucial role in the global radiative balance due to its ability to absorb light. However, the effect of molecular formation on the light absorption properties of BrC remains poorly understood. In this study, atmospheric BrC samples collected from six Chinese megacities in winter and summer were characterized through ultrahigh-performance liquid chromatography coupled with Orbitrap mass spectrometry (UHPLC-Orbitrap MS) and light absorption measurements. The average values of BrC light absorption coefficient at a wavelength of 365 nm (babs365) in winter were approximately 4.0 times higher than those in summer. Nitrogen-containing organic molecules (CHNO) were identified as critical components of light-absorbing substances in both seasons, underscoring the importance of N-addition in BrC. These nitrogen-containing BrC chromophores were more closely related to nitro-containing compounds originating from biomass burning and nitrogen oxides (NOx)/nitrate (NO3-) reactions in winter. In summer, they were related to reduced N-containing compounds formed in ammonia (NH3)/ammonium (NH4+) reactions. The NH3/NH4+-mediated reactions contributed more to secondary BrC in summer than winter, particularly in southern cities. Compared with winter, the higher O/Cw, lower molecule conjugation indicator (double bond equivalent, DBE), and reduced BrC babs365 in summer suggest a possible bleaching mechanism during the oxidation process. These findings strengthen the connection between molecular composition and the light-absorbing properties of BrC, providing insights into the formation mechanisms of BrC chromophores across northern and southern Chinese cities in different seasons.

Injectable Xenogeneic Dental Pulp Decellularized Extracellular Matrix Hydrogel Promotes Functional Dental Pulp Regeneration.

The present challenge in dental pulp tissue engineering scaffold materials lies in the development of tissue-specific scaffolds that are conducive to an optimal regenerative microenvironment and capable of accommodating intricate root canal systems. This study utilized porcine dental pulp to derive the decellularized extracellular matrix (dECM) via appropriate decellularization protocols. The resultant dECM was dissolved in an acid pepsin solution to form dECM hydrogels. The analysis encompassed evaluating the microstructure and rheological properties of dECM hydrogels and evaluated their biological properties, including in vitro cell viability, proliferation, migration, tube formation, odontogenic, and neurogenic differentiation. Gelatin methacrylate (GelMA) hydrogel served as the control. Subsequently, hydrogels were injected into treated dentin matrix tubes and transplanted subcutaneously into nude mice to regenerate dental pulp tissue in vivo. The results showed that dECM hydrogels exhibited exceptional injectability and responsiveness to physiological temperature. It supported the survival, odontogenic, and neurogenic differentiation of dental pulp stem cells in a 3D culture setting. Moreover, it exhibited a superior ability to promote cell migration and angiogenesis compared to GelMA hydrogel in vitro. Additionally, the dECM hydrogel demonstrated the capability to regenerate pulp-like tissue with abundant blood vessels and a fully formed odontoblast-like cell layer in vivo. These findings highlight the potential of porcine dental pulp dECM hydrogel as a specialized scaffold material for dental pulp regeneration.

Bionic Assembly of Layered Double Hydroxides Nanosheets and Positively Charged Micelles by Counterions Balance and Their Selective Detection of Mannose.

The selective detection of mannose is significant for tumor early diagnosis. However, current methods for detecting mannose are expensive and time-consuming, limiting their application. In this paper, we have obtained a 25-layer positively charged micellar/LDHs nanocomposite film system by electrostatic layer-by-layer assembly with reference to the unique properties of homogeneous charge ion attraction and charge overcompensation in biomolecules: hexadecyl trimethylammonium bromide (CTAB) was used to coat neutral molecules of fluorescein (FLU) to form (FLU@CTAB) cationic micelles, which were electrostatically assembled with laminate positively charged layered double hydroxides (LDHs) nanosheets to form (FLU@CTAB/LDHs)n ultrathin films (UTFs) by the layer-by-layer electrostatic assembly, where the mediating role of the Br- counteranion had a profound effect on the success of the assembly. Moreover, compared to pure FLU solution, the fluorescence intensity and the lifetime of (FLU@CTAB/LDHs)20 UTFs were enhanced by 1.6 and 2 times, respectively. (FLU@CTAB/LDHs)20 UTFs exhibited selective detection for d-mannose with a detection limit of 0.05 mg·mL-1. Therefore, the (FLU@CTAB/LDHs)n UTFs can be a novel biosensor. Compared to conventional powder sensors, (FLU@CTAB/LDHs)n thin-film fluorescent sensors are more promising for device implementation. Moreover, the design strategy of positively charged micellar/LDHs nanocomposite systems breaks the current limitation that LDHs can only be assembled with anions or neutral molecules and extends the scope of counterion-mediated host-guest to the nanosheet-micellar system.

Extracellular lipopeptide bacillomycin L regulates serial expression of genes for modulating multicellular behavior in Bacillus velezensis Bs916.

In wild strains of Bacillus, a handful of extracellular natural products act as signals that can regulate multicellular behavior, but relatively little is known about molecular mechanisms' detail. We proposed a previously unreported molecular mechanism for triggering multicellularity in B. velezensis Bs916 by an endogenous cyclic lipopeptide, bacillomycin L. The genome-wide effect on gene expression was caused by the disruption of bacillomycin L gene cluster, and 100 µg/mL bacillomycin L was revealed by quantitative transcriptomics. A total of 878 differentially expressed genes among Bs916, Δbl, and Δbl + 100BL were identified and grouped into 9 functional categories. The transcription levels of 40 candidate genes were further evaluated by RT-qPCR analysis. The expression of eight candidate genes regulated by bacillomycin L in a dose-dependent manner was revealed by LacZ fusion experiment. Although the addition of bacillomycin L could not completely restore the expression levels of the differentially regulated genes in △bl, our results strongly suggest that bacillomycin L acts as a tuning signal of swarming motility and complex biofilm formation by indirectly regulating the expression levels of some two-component systems (TCSs) connector genes, particularly including several Raps that potentially regulate the phosphorylation levels of three major regulators ComA, DegU, and Spo0A.Key points• Proposed model for bacillomycin L regulation in B. velezensis Bs916.• Bacillomycin L can act as an extracellular signal to regulate the phosphorylation levels of three major regulators, ComA, DegU, and Spo0A and control the multicellular processes of vegetative growth, competent, motility, matrix production, sporulation, and autolysis.

Rapid analysis and characterization of multiple constituents of corn silk aqueous extract using ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry.

Corn silk is a well-known traditional Chinese medicine that has been widely used for its antidiabetic, antioxidant, antihyperlipidemic, and other effects in China for thousands of years. Numerous studies have revealed that corn silk contains multiple bioactive constituents that are beneficial for human health. However, the constituents of corn silk in vivo remain ambiguous. In this study, high-throughput ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry technology using multivariate statistical analysis was established to systematically investigate the constituents migrating into blood from corn silk aqueous extract. As a result, 76 compounds were identified, including caffeic acid and ten of its derivatives, (E)-p-coumaric acid and two of its derivatives, ferulic acid and four of its derivatives, and five flavones. Among the identified constituents, 21 constituents, including nine prototype components and 12 metabolites derived from eight components, were characterized in sequence. Based on the significance of the results, the applied approach was powerful for the accurate determination and rapid screening of bioactive components from corn silk aqueous extract. The obtained results are valuable for the in-depth understanding and further pharmacological study of corn silk aqueous extract.

Bacillus methanolicus: an emerging chassis for low-carbon biomanufacturing.

Bacillus methanolicus is a thermophilic methylotrophic bacterium that grows quickly on methanol in sea water-based media. It has been engineered for chemical bioproduction from methanol, but its efficiency needs improvement for industrialization. Synthetic biology approaches such as metabolic modeling and genome editing can reprogram B. methanolicus for low-carbon biomanufacturing.

Compartment syndrome associations with drugs: a pharmacovigilance study of the FDA adverse event reporting system (FAERS).

BACKGROUND: Compartment syndrome is an uncommon but life-threatening condition. No study has comprehensively compared compartment syndrome (CS) association with available drugs. The objective of this study was to estimate the association between CS and drugs using the FDA Adverse Event Report System (FAERS). RESEARCH DESIGN AND METHODS: FAERS reports from the first quarter of 2004 to the third quarter of 2023 were analyzed. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify CS cases. Reporting odds ratio (ROR), corresponding to 95% confidence intervals (95% CI) were calculated to detect a positive signal. RESULTS: A total of 2197 reports were considered in the study after the inclusion criteria were applied. Totally 100 drugs were found to be associated with CS. The median time for drug-associated CS was 45 days. CONCLUSIONS: By analyzing the FAERS database, the study revealed that certain drugs are significantly associated with compartment syndrome. Further studies are needed to verify whether these drugs are associated with such a risk.

Triple-Responsive, Multimodal, Visual Electronic Skin toward All-in-One Health Management for Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is one of the most common metabolic disorders during pregnancy, leading to serious complications for pregnant women and a threat to life safety of infants. Therefore, it is particularly important to establish a multipurpose monitoring pathway to important physiological indicators of pregnant women. In this work, three kinds of double network hydrogels are prepared with poly(vinyl alcohol) (PVA), borax, and cellulose ethers with varying substituents of methyl (methyl cellulose, MC), hydroxypropyl (hydroxypropyl cellulose, HPC), or both (hydroxypropyl methyl cellulose, HPMC), respectively. The corresponding toughness (143.9, 102.3, and 135.9 kJ cm-3) and conductivity (0.69, 0.45, and 0.51 S m-1) of the hydrogels demonstrate that PB-MC was endowed with the prominent performance. Molecular dynamics simulations further revealed the essence that hydrogen bond interactions between PVA and cellulose ethers play a critical role in regulating the structure and properties of hydrogels. Thermochromic capsule powders (TCPs) were subsequently doped in to achieve a composite hydrogel (TCPs@PB-MC) to indicate the change in human body temperature. Furthermore, the process of the TCPs@PB-MC response to glucose, pH, and temperature was tracked in-depth through the electrochemical window. This work provides a novel strategy for all-in-one health management of GDM.

Prenatal diagnosis of recurrent Kagami-Ogata syndrome inherited from a mother affected by Temple syndrome: a case report and literature review.

BACKGROUND: Kagami-Ogata syndrome (KOS) and Temple syndrome (TS) are two imprinting disorders characterized by the absence or reduced expression of maternal or paternal genes in the chromosome 14q32 region, respectively. We present a rare prenatally diagnosed case of recurrent KOS inherited from a mother affected by TS. CASE PRESENTATION: The woman's two affected pregnancies exhibited recurrent manifestations of prenatal overgrowth, polyhydramnios, and omphalocele, as well as a small bell-shaped thorax with coat-hanger ribs postnatally. Prenatal genetic testing using a single-nucleotide polymorphism array detected a 268.2-kb deletion in the chromosome 14q32 imprinted region inherited from the mother, leading to the diagnosis of KOS. Additionally, the woman carried a de novo deletion in the paternal chromosome 14q32 imprinted region and presented with short stature and small hands and feet, indicating a diagnosis of TS. CONCLUSIONS: Given the rarity of KOS as an imprinting disorder, accurate prenatal diagnosis of this rare imprinting disorder depends on two factors: (1) increasing clinician recognition of the clinical phenotype and related genetic mechanism, and (2) emphasizing the importance of imprinted regions in the CMA workflow for laboratory analysis.

Panoramic variation analysis of a family with neurodevelopmental disorders caused by biallelic loss-of-function variants in TMEM141, DDHD2, and LHFPL5.

Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and medicine. Panoramic variation analysis is imperative to analyze the disease phenotypes resulting from multilocus genomic variation. Here, a Pakistani family with parental consanguinity was presented, characterized with severe intellectual disability (ID), spastic paraplegia, and deafness. Homozygosity mapping, integrated single nucleotide polymorphism (SNP) array, whole-exome sequencing, and whole-genome sequencing were performed, and homozygous variants in TMEM141 (c.270G>A, p.Trp90*), DDHD2 (c.411+767_c.1249-327del), and LHFPL5 (c.250delC, p.Leu84*) were identified. A Tmem141p.Trp90*/p.Trp90* mouse model was generated. Behavioral studies showed impairments in learning ability and motor coordination. Brain slice electrophysiology and Golgi staining demonstrated deficient synaptic plasticity in hippocampal neurons and abnormal dendritic branching in cerebellar Purkinje cells. Transmission electron microscopy showed abnormal mitochondrial morphology. Furthermore, studies on a human in vitro neuronal model (SH-SY5Y cells) with stable shRNA-mediated knockdown of TMEM141 showed deleterious effect on bioenergetic function, possibly explaining the pathogenesis of replicated phenotypes in the cross-species mouse model. Conclusively, panoramic variation analysis revealed that multilocus genomic variations of TMEM141, DDHD2, and LHFPL5 together caused variable phenotypes in patient. Notably, the biallelic loss-of-function variants of TMEM141 were responsible for syndromic ID.

Nitroaromatic compounds in six major Chinese cities: Influence of different formation mechanisms on light absorption properties.

Nitroaromatic compounds (NACs) are important nitrogen organics in aerosol with strong light-absorbing and chemically reactive properties. In this study, NACs in six Chinese megacities, including Harbin (HB), Beijing (BJ), Xi'an (XA), Wuhan (WH), Chengdu (CD), and Guangzhou (GZ), were investigated for understanding their sources, gas-particle partitioning, and impact on BrC absorption properties. The concentrations of ΣNACs in PM2.5 in the six cities ranged from 9.15 to 158.8 ng/m3 in winter and from 2.02 to 9.39 ng/m3 in summer. Nitro catechols (NCs), nitro phenols (NPs), and nitro salicylic acids (NSAs) are the main components in ΣNACs, with NCs being dominant in particulate phase and NPs being dominant in the gas phase. Correlation analysis between different pollutant species revealed that coal and biomass combustions were the major sources of NACs in the northern cities during wintertime, while secondary formation dominated NACs in the southern cities during summertime. The contribution of ΣNACs to brown carbon (BrC) light absorption ranged from 0.85 to 7.98 % during the wintertime and 2.07-6.44 % during the summertime. The mass absorption efficiency at 365 nm (MAE365) were highest for 4-nitrocatechol (4NC, 17.4-89.0 m2/g), 4-methyl-5-nitrocatechol (4M5NC, 15.0-76.9 m2/g), and 4-nitroguaiacol (4NG, 11.7-59.8 m2/g). The formation of NCs and NG through oxidation and nitration of catechol and guaiacol led to a significant increase in aerosol light absorption. In contrast, NPs and NSAs formed by the photonitration and photooxidation in liquid phase showed high polarity but low light absorption ability, and the proportions of (NPs + NSAs) in the light absorption of ΣNACs were lower than 15.3 % in the six megacities.

FAXDC2 inhibits the proliferation and invasion of human liver cancer HepG2 cells.

The reprogramming of lipid metabolism serves an important role in occurrence and development of liver cancer. Fatty acid hydroxylase domain containing 2 (FAXDC2) is a hydroxylase involved in the synthesis of cholesterol and sphingomyelin and downregulated in various types of cancer. There are no reports on the relationship between FAXDC2 and liver carcinogenesis. The present study used multiple portals and publicly available tools to explore its correlation with liver cancer. The results showed that the expression of FAXDC2 decreased in liver cancer and the methylation level near the promoter increased. Patients with liver cancer and with low expression of FAXDC2 had a poor prognosis. Gain of function and loss of function strategies were performed to evaluate its roles in liver cancer cells. CCK-8 assay showed that overexpression of FAXDC2 inhibited the viability of liver cancer cells (HepG2). Flow cytometry analysis indicated that HepG2 cells with overexpressing FAXDC2 showed an S phase arrest, associated with cyclin-dependent kinase 2 decreased. Transwell experiments showed that increasing FAXDC2 inhibited HepG2 cell invasion ability, accompanied by the upregulation of E-cadherin. Notably, knockdown of FAXDC2 had no significant effect on cell cycle and invasion functions. Based on the cBioPortal platform, FAXDC2 was predicted to closely correlate to the ERK signal in tumorigenesis. Western blotting results showed that overexpression of FAXDC2 decreased the phosphorylation level of ERK in liver cancer cells. The present study first identified FAXDC2 as a liver cancer suppressor, which might inhibit the proliferation and invasion of liver cancer cells through the mechanism associated with ERK signaling. The present study provided a possible new target for the diagnosis and treatment of liver cancer.

Proteomic and metabolomic features in patients with HCC responding to lenvatinib and anti-PD1 therapy.

Combination therapy (lenvatinib/programmed death-1 inhibitor) is effective for treating unresectable hepatocellular carcinoma (uHCC). We reveal that responders have better overall and progression-free survival, as well as high tumor mutation burden and special somatic variants. We analyze the proteome and metabolome of 82 plasma samples from patients with hepatocellular carcinoma (HCC; n = 51) and normal controls (n = 15), revealing that individual differences outweigh treatment differences. Responders exhibit enhanced activity in the alternative/lectin complement pathway and higher levels of lysophosphatidylcholines (LysoPCs), predicting a favorable prognosis. Non-responders are enriched for immunoglobulins, predicting worse outcomes. Compared to normal controls, HCC plasma proteins show acute inflammatory response and platelet activation, while LysoPCs decrease. Combination therapy increases LysoPCs/phosphocholines in responders. Logistic regression/random forest models using metabolomic features achieve good performance in the prediction of responders. Proteomic analysis of cancer tissues unveils molecular features that are associated with side effects in responders receiving combination therapy. In conclusion, our analysis identifies plasma features associated with uHCC responders to combination therapy.

Effects of geraniin on osteoclastic bone resorption and matrix metalloproteinase-9 expression.

In our previous studies, geraniin was reported to have a preventive effect in the rat model of tretinoin-induced osteoporosis. However, whether geraniin exhibits an inhibitory effect on bone resorption or on MMP-9 expression is not yet known. We present here our novel findings from in vitro experiments that geraniin (a) decreases the number of mature osteoclasts and pre-osteoclast in cultures, (b) reduces the osteoclastic fusion index, and (c) inhibits the resorption areas and resorption pits. We also report that geraniin suppresses the mRNA and protein expression levels of MMP-9. These results demonstrate that geraniin has an inhibitory effect on the bone-absorption ability of osteoclasts in vitro, and the mechanisms may be closely associated with the downregulation of mRNA and protein expression of MMP-9.

Discrepant diversity patterns and function of bacterial and fungal communities on an earthquake-prone mountain gradient in Northwest Sichuan, China.

Patterns of microbial diversity on elevational gradients have been extensively studied, but little is known about those patterns during the restoration of earthquake-fractured alpine ecosystems. In this study, soil properties, soil enzyme activities, abundance and diversity of soil bacterial and fungal communities at four positions along a 2.6-km elevational gradient in the Snow Treasure Summit National Nature Reserve, located in Pingwu County, Southwest China. Although there were no significant changes in the soil chemical environment, bacterial and fungal communities were significantly different at different elevations. The overall fungal community presented an N-shaped diversity pattern with increasing elevation, while bacterial diversity decreased significantly with elevation. Changes in microbial diversity were associated with soil phosphorus, plant litter, and variations in dominant microbial taxa. Differences in enzyme activities among elevations were regulated by microbial communities, with changes in catalase and acid phosphatase activities mainly controlled by Acidobacteria and Planctomycetaceae bacteria, respectively (catalase: p < 0.001; acid phosphatase: p < 0.01), and those in ß-glucosidase, sucrase, and urease activities mainly controlled by fungi. The ß-glucosidase and sucrase were both positively correlated with Herpotrichiellaceae, and urease was positively correlated with Sebacinaceae (p < 0.05). These findings contribute to the conservation and management of mountain ecosystems in the face of changing environmental conditions. Further research can delve into the specific interactions between microbial communities, soil properties, and vegetation to gain deeper insights into the intricate ecological dynamics within earthquake-prone mountain ecosystems.

14-3-3 proteins regulate the HCHO stress response by interacting with AtMDH1 and AtGS1 in tobacco and Arabidopsis.

Formaldehyde (HCHO) is one of the most essential common carcinogenic environmental pollutants. While 14-3-3 proteins are known to regulate the response of plants to HCHO stress, the regulatory mechanisms responsible for a tolerant phenotype remain unclear. We first performed qPCR analysis of HCHO-treated Arabidopsis and tobacco and determined that the expression of At14-3-3PSI and Nt14-3-3C genes was rapidly upregulated after HCHO stress. Furthermore, overexpression of 14-3-3, AtMDH1 or AtGS1 genes enhanced plant HCHO absorption capacity and resistance, and knockdown or knockout of 14-3-3, AtMDH1 or AtGS1 genes reduced plant HCHO absorption capacity and resistance. However, overexpression of the AtGS1 and AtMDH1 genes in the At14-3-3 psi mutant restored HCHO uptake and resistance in Arabidopsis. Moreover, 14-3-3 bound to the N-terminus of AtMDH1 and the C-terminus of AtGS1, respectively, and repressed and enhanced their expression. The 13C NMR results of HCHO stress mutants Atgs1 and Atmdh1 showed that the metabolites Glu and Asp rapidly increased, indicating that AtGS1 and AtMDH1 were indeed indispensable for Arabidopsis to metabolize HCHO. In conclusion, we uncovered a HCHO stress response mechanism mediated by 14-3-3, which enhances the plant's ability to absorb HCHO, deepening our understanding of how plants respond to HCHO stress.

Easy regulation of chitosan-based hydrogel microstructure with citric acid as an efficient buffer.

Being an important soft material, the chitosan-based hydrogel exhibits colorful features and widespread applications stemmed mainly from its intrinsic microstructure. In particular, the design of hydrogels with oriented channel structures is of significance importance. In this paper, polyvinyl alcohol (PVA)/chitosan (CS)/MXene-CA hydrogels with directional channel structure were obtained by simple freezing and thawing method with citric acid (CA) as a buffer. The introduction of CS increased the tensile strength of PVA hydrogel from 5.38 kPa to 29.22 kPa. The uniform distribution of MXene was efficiently enhanced within the constructed channel microstructure, and conductivity was increased to 1.91 S/m. The response time of the flexible sensor based on the hydrogel was 200 ms. It can sensitively detect large-scale deformation (blending of joints), small-scale activity (frowning), and electrocardiogram. Therefore, the paper provided an efficient way to regulate the microstructure in hydrogel network and enhance the uniform dispersion of functional nanomaterials.

Cost-effectiveness analysis of ceftazidime-avibactam as definitive treatment for treatment of carbapenem-resistant Klebsiella pneumoniae bloodstream infection.

Background: Ceftazidime-avibactam (CAZ-AVI) is a novel antibiotic that has been confirmed in the United States and China for use in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection (BSI). However, the cost-effectiveness of CAZ-AVI is unknown in China. This study aimed to evaluate the cost-effectiveness of CAZ-AVI compared to polymyxin B (PMB) monotherapy or PMB-based therapy for the treatment of CRKP BSI from the Chinese healthcare perspective. Methods: A hybrid decision tree and Markov model were constructed for a hypothetical cohort of patients with CRKP BSI. The time horizon of the Markov model was 5 years with an annual discount rate of 5% used in both costs and quality-adjusted life-years (QALYs). The model data was derived from published literature and publicly available database. Regimens with an incremental cost-effectiveness ratio (ICER) lower than the willingness-to-pay (WTP) threshold of $ 11,600 per QALY were considered cost-effective. Deterministic and probabilistic sensitivity analyses were performed to examine the robustness of model analysis. Results: In the base-analysis, CAZ-AVI provided an additional 60 QALYs and reduced the cost by $ 2,218,300, yielding an ICER of $ -36,730.9/QALY, well below the WTP threshold of $ 11,600 per QALY when compared with PMB-based therapy. CAZ-AVI provided an additional 350 QALYs and increased the cost of $ 208,400, producing an ICER of $ 591.7/QALY that was below the WTP threshold compared to PMB monotherapy. At a $ 11,600/QALY threshold, results were sensitive to the cost of PMB-based strategy, the cost of CAZ-AVI strategy, the probability of cure with CAZ-AVI, and the probability of cure with PMB or PMB-based therapy. CAZ-AVI was an optimal regimen in 76.9% and 80.8% of 10,000 Monte Carlo simulations at $ 11,600/QALY and $ 34,800/QALY, respectively. Meanwhile, CAZ-AVI was cost-effective at the WTP thresholds of all 31 Chinese provinces in 61.4% (Gansu) to 83.1% (Beijing) of simulations. Conclusions: Ceftazidime-avibactam is expected to be a cost-effective treatment compared with PMB monotherapy or PMB-based therapy for CRKP BSI from the Chinese healthcare perspective.

Soil quality evaluation of different land use patterns on the southern and northern Qinghai-Tibet Plateau based on minimal data set.

To evaluate soil quality status of forest, grassland, and cropland in the southern and northern Tibetan Plateau, and to clarify the key influencing factors of productivity levels under three land use types, we measured the basic physical and chemical properties of 101 soil samples collected in the northern and southern Qinghai-Tibet Plateau. Principal component analysis (PCA) was used to select three indicators as the minimum data set (MDS) to comprehensively evaluate soil quality of the southern and northern Qinghai-Tibet Plateau. The result showed that soil physical and chemical properties of the three land use types were significantly different in the north and south. The contents of soil organic matter (SOM), total nitrogen (TN), available phosphorus (AP) and available potassium (AK) in the north were higher than those in the south, while the contents of SOM and TN of forest were signi-ficantly higher than those of cropland and grassland in both the north and south. Soil ammonium (NH4+-N) content showed a pattern of cropland > forest > grassland, with significant difference in the south. Soil nitrate (NO3--N) content in the north and south was the highest in the forest. Soil bulk density (BD) and electrical conductivity (EC) of cropland were significantly higher than those of grassland and forest, and that of cropland and grassland in the northern part was higher than that of southern part. Soil pH of grassland in the south was significantly higher than that of forest and cropland, and that of forest was the highest in northern part. The selected indicators for eva-luating soil quality in the north were SOM, AP, and pH, and soil quality index of forest, grassland, and cropland was 0.56, 0.53 and 0.47. The selected indicators were SOM, total phosphorus (TP), and NH4+-N in the south, and soil quality index of grassland, forest and cropland was 0.52, 0.51 and 0.48, respectively. There was a significant correlation between soil quality index obtained by the total data set and the minimum data set, and the regression coefficient was 0.69. Soil quality in the north and south of the Qinghai-Tibet Plateau were grade Ⅲ, and soil organic matter was the main indicator limiting soil quality in this area. Our results provide a scientific basis for eva-luating soil quality and ecological restoration in the Qinghai-Tibet Plateau.

Insight into the mechanism of gallstone disease by proteomic and metaproteomic characterization of human bile.

Introduction: Cholesterol gallstone disease is a prevalent condition that has a significant economic impact. However, the role of the bile microbiome in its development and the host's responses to it remain poorly understood. Methods: In this study, we conducted a comprehensive analysis of microbial and human bile proteins in 40 individuals with either gallstone disease or gallbladder polyps. We employed a combined proteomic and metaproteomic approach, as well as meta-taxonomic analysis, functional pathway enrichment, and Western blot analyses. Results: Our metaproteomic analysis, utilizing the lowest common ancestor algorithm, identified 158 microbial taxa in the bile samples. We discovered microbial taxa that may contribute to gallstone formation, including ß-glucuronidase-producing bacteria such as Streptococcus, Staphylococcus, and Clostridium, as well as those involved in biofilm formation like Helicobacter, Cyanobacteria, Pseudomonas, Escherichia coli, and Clostridium. Furthermore, we identified 2,749 human proteins and 87 microbial proteins with a protein false discovery rate (FDR) of 1% and at least 2 distinct peptides. Among these proteins, we found microbial proteins crucial to biofilm formation, such as QDR3, ompA, ndk, pstS, nanA, pfIB, and dnaK. Notably, QDR3 showed a gradual upregulation from chronic to acute cholesterol gallstone disease when compared to polyp samples. Additionally, we discovered other microbial proteins that enhance bacterial virulence and gallstone formation by counteracting host oxidative stress, including sodB, katG, rbr, htrA, and ahpC. We also identified microbial proteins like lepA, rtxA, pckA, tuf, and tpiA that are linked to bacterial virulence and potential gallstone formation, with lepA being upregulated in gallstone bile compared to polyp bile. Furthermore, our analysis of the host proteome in gallstone bile revealed enhanced inflammatory molecular profiles, including innate immune molecules against microbial infections. Gallstone bile exhibited overrepresented pathways related to blood coagulation, folate metabolism, and the IL-17 pathway. However, we observed suppressed metabolic activities, particularly catabolic metabolism and transport activities, in gallstone bile compared to polyp bile. Notably, acute cholelithiasis bile demonstrated significantly impaired metabolic activities compared to chronic cholelithiasis bile. Conclusion: Our study provides a comprehensive metaproteomic analysis of bile samples related to gallstone disease, offering new insights into the microbiome-host interaction and gallstone formation mechanism.