Exploring Advanced Therapies for Primary Biliary Cholangitis: Insights from the Gut Microbiota-Bile Acid-Immunity Network.

Primary biliary cholangitis (PBC) is a cholestatic liver disease characterized by immune-mediated injury to small bile ducts. Although PBC is an autoimmune disease, the effectiveness of conventional immunosuppressive therapy is disappointing. Nearly 40% of PBC patients do not respond to the first-line drug UDCA. Without appropriate intervention, PBC patients eventually progress to liver cirrhosis and even death. There is an urgent need to develop new therapies. The gut-liver axis emphasizes the interconnection between the gut and the liver, and evidence is increasing that gut microbiota and bile acids play an important role in the pathogenesis of cholestatic diseases. Dysbiosis of gut microbiota, imbalance of bile acids, and immune-mediated bile duct injury constitute the triad of pathophysiology in PBC. Autoimmune cholangitis has the potential to be improved through immune system modulation. Considering the failure of conventional immunotherapies and the involvement of gut microbiota and bile acids in the pathogenesis, targeting immune factors associated with them, such as bile acid receptors, microbial-derived molecules, and related specific immune cells, may offer breakthroughs. Understanding the gut microbiota-bile acid network and related immune dysfunctions in PBC provides a new perspective on therapeutic strategies. Therefore, we summarize the latest advances in research of gut microbiota and bile acids in PBC and, for the first time, explore the possibility of related immune factors as novel immunotherapy targets. This article discusses potential therapeutic approaches focusing on regulating gut microbiota, maintaining bile acid homeostasis, their interactions, and related immune factors.

GTPBP8 modulates mitochondrial fission through a Drp1-dependent process.

Mitochondrial fission is a tightly regulated process involving multiple proteins and cell signaling. Despite extensive studies on mitochondrial fission factors, our understanding of the regulatory mechanisms remains limited. This study shows the critical role of a mitochondrial GTPase, GTPBP8, in orchestrating mitochondrial fission in mammalian cells. Depletion of GTPBP8 resulted in drastic elongation and interconnectedness of mitochondria. Conversely, overexpression of GTPBP8 shifted mitochondrial morphology from tubular to fragmented. Notably, the induced mitochondrial fragmentation from GTPBP8 overexpression was inhibited in cells either depleted of the mitochondrial fission protein Drp1 (also known as DNM1L) or carrying mutated forms of Drp1. Importantly, downregulation of GTPBP8 caused an increase in oxidative stress, modulating cell signaling involved in the increased phosphorylation of Drp1 at Ser637. This phosphorylation hindered the recruitment of Drp1 to mitochondria, leading to mitochondrial fission defects. By contrast, GTPBP8 overexpression triggered enhanced recruitment and assembly of Drp1 at mitochondria. In summary, our study illuminates the cellular function of GTPBP8 as a pivotal modulator of the mitochondrial division apparatus, inherently reliant on its influence on Drp1.

Ammonia-induced oxidative stress triggered apoptosis in the razor clam (Sinonovacula constricta).

As one of the most significant contaminants and stressors in aquaculture systems, ammonia adversely jeopardizes the health of aquatic animals. Ammonia exposure affects the development, metabolism, and survival of shellfish. However, the responses of the innate immune and antioxidant systems and apoptosis in shellfish under ammonia stress have rarely been reported. In this study, razor clams (Sinonovacula constricta) were exposed to different concentrations of non-ion ammonia (0.25 mg/L, 2.5 mg/L) for 72 h and then placed in ammonia-free seawater for 72 h for recovery. The immune responses induced by ammonia stress on razor clams were investigated by antioxidant enzyme activities and degree of apoptosis in digestive gland and gill tissues at different time points. The results showed that exposure to a high concentration of ammonia greatly disrupted the antioxidant system of the razor clam by exacerbating the accumulation of reactive oxygen species ( O 2 - , H2O2) and disordering the activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), and the level of activity remained at a significantly high level after recovering for 72 h (P < 0.05). In addition, there were significant differences (P < 0.05) in the expression of key genes (Caspase 7, Cyt-c, Bcl-2, and Bax) in the mitochondrial apoptotic pathway in the digestive glands and gills of razor clams as a result of ammonia stress and were unable to return to normal levels after 72 h of recovery. TUNEL staining indicated that apoptosis was more pronounced in gills, showing a dose and time-dependent pattern. As to the results, ammonia exposure leads to the activation of innate immunity in razor clams, disrupts the antioxidant system, and activates the mitochondrial pathway of apoptosis. This is important for comprehending the mechanism underlying the aquatic toxicity resulting from ammonia in shellfish.

Correlation enhanced distribution adaptation for prediction of fall risk.

With technological advancements in diagnostic imaging, smart sensing, and wearables, a multitude of heterogeneous sources or modalities are available to proactively monitor the health of the elderly. Due to the increasing risks of falls among older adults, an early diagnosis tool is crucial to prevent future falls. However, during the early stage of diagnosis, there is often limited or no labeled data (expert-confirmed diagnostic information) available in the target domain (new cohort) to determine the proper treatment for older adults. Instead, there are multiple related but non-identical domain data with labels from the existing cohort or different institutions. Integrating different data sources with labeled and unlabeled samples to predict a patient's condition poses a significant challenge. Traditional machine learning models assume that data for new patients follow a similar distribution. If the data does not satisfy this assumption, the trained models do not achieve the expected accuracy, leading to potential misdiagnosing risks. To address this issue, we utilize domain adaptation (DA) techniques, which employ labeled data from one or more related source domains. These DA techniques promise to tackle discrepancies in multiple data sources and achieve a robust diagnosis for new patients. In our research, we have developed an unsupervised DA model to align two domains by creating a domain-invariant feature representation. Subsequently, we have built a robust fall-risk prediction model based on these new feature representations. The results from simulation studies and real-world applications demonstrate that our proposed approach outperforms existing models.

Bile Acid Diarrhea: From Molecular Mechanisms to Clinical Diagnosis and Treatment in the Era of Precision Medicine.

Bile acid diarrhea (BAD) is a multifaceted intestinal disorder involving intricate molecular mechanisms, including farnesoid X receptor (FXR), fibroblast growth factor receptor 4 (FGFR4), and Takeda G protein-coupled receptor 5 (TGR5). Current diagnostic methods encompass bile acid sequestrants (BAS), 48-h fecal bile acid tests, serum 7α-hydroxy-4-cholesten-3-one (C4), fibroblast growth factor 19 (FGF19) testing, and 75Selenium HomotauroCholic acid test (75SeHCAT). Treatment primarily involves BAS and FXR agonists. However, due to the limited sensitivity and specificity of current diagnostic methods, as well as suboptimal treatment efficacy and the presence of side effects, there is an urgent need to establish new diagnostic and treatment methods. While prior literature has summarized various diagnostic and treatment methods and the pathogenesis of BAD, no previous work has linked the two. This review offers a molecular perspective on the clinical diagnosis and treatment of BAD, with a focus on FXR, FGFR4, and TGR5, emphasizing the potential for identifying additional molecular mechanisms as treatment targets and bridging the gap between diagnostic and treatment methods and molecular mechanisms for a novel approach to the clinical management of BAD.

Bacterial templated carbonate mineralization: insights from concave-type crystals induced by Curvibacter lanceolatus strain HJ-1.

The elucidation of carbonate crystal growth mechanisms contributes to a deeper comprehension of microbial-induced carbonate precipitation processes. In this research, the Curvibacter lanceolatus HJ-1 strain, well-known for its proficiency in inducing carbonate mineralization, was employed to trigger the formation of concave-type carbonate minerals. The study meticulously tracked the temporal alterations in the culture solution and conducted comprehensive analyses of the precipitated minerals' mineralogy and morphology using advanced techniques such as X-ray diffraction, scanning electron microscopy, focused ion beam, and transmission electron microscopy. The findings unequivocally demonstrate that concave-type carbonate minerals are meticulously templated by bacterial biofilms and employ calcified bacteria as their fundamental structural components. The precise morphological evolution pathway can be delineated as follows: initiation with the formation of bacterial biofilms, followed by the aggregation of calcified bacterial clusters, ultimately leading to the emergence of concave-type minerals characterized by disc-shaped, sunflower-shaped, and spherical morphologies.

Morphological and vascular evidence of glaucomatous damage in myopic guinea pigs with scleral crosslinking.

Guinea pigs are often used as models for myopia studies. However, the imaging structure and vasculature of the optic nerve head (ONH) in guinea pigs are tentative. This study investigated morphological parameters and vascular characteristics of the ONH in guinea pigs with form deprivation (FD) myopia before and after scleral crosslinking (CXL), using optical coherence tomography (OCT) and OCT angiography (OCTA). Refractive error, axial length (AL), intraocular pressure (IOP), and OCT-based structural parameters of the ONH were measured at baseline and 3 weeks after the FD + CXL procedure in guinea pigs. The 88 guinea pigs analysed in this study were aged 3 (n = 29), 4 (n = 51), and 5 (n = 8) weeks. The IOP, AL, average and vertical cup-to-disc ratio (C/D), circumpapillary retinal nerve fibre layer, disc area, and cup volume increased at 3 weeks compared to baseline values (all p < 0.001). The refractive error and rim area decreased at 3 weeks compared to baseline values (all p < 0.001). After adjustment for age, IOP was correlated positively with average C/D (p = 0.039) and negatively with rim area (p = 0.009). The severity of blood signal defects was positively associated with the average C/D at 3 weeks (p = 0.027). These findings may facilitate further research on myopia using guinea pigs.

Noncovalent Conjugates of Anthocyanins to Wheat Gluten: Unraveling Their Microstructure and Physicochemical Properties.

Intake of polyphenol-modified wheat products has the potential to reduce the incidence of chronic diseases. In order to determine the modification effect of polyphenols on wheat gluten protein, the effects of grape skin anthocyanin extract (GSAE, additional amounts of 0.1%, 0.2%, 0.3%, 0.4%, and 0.5%, respectively) on the microstructure and physicochemical properties of gluten protein were investigated. The introduction of GSAE improves the maintenance of the gluten network and increases viscoelasticity, as evidenced by rheological and creep recovery tests. The tensile properties of gluten protein were at their peak when the GSAE level was 0.3%. The addition of 0.5% GSAE may raise the denaturation temperature of gluten protein by 6.48 °C-9.02 °C at different heating temperatures, considerably improving its thermal stability. Furthermore, GSAE enhanced the intermolecular hydrogen bond of gluten protein and promoted the conversion of free sulfhydryl groups to disulfide bonds. Meanwhile, the GSAE treatment may also lead to protein aggregation, and the average pore size of gluten samples decreased significantly and the structure became denser, indicating that GSAE improved the stability of the gluten spatial network. The positive effects of GSAE on gluten protein properties suggest the potential of GSAE as a quality enhancer for wheat products.

Fabrication of ammonia and acetic acid-responsive intelligent films based on grape skin anthocyanin via adjusting the pH of film-forming solution.

pH-responsive intelligent films for food freshness monitoring have attracted great attentions recently. In this study, several intelligent films based on chitosan (CS), polyvinyl alcohol (PVA), and grape skin anthocyanin (GSA) were prepared, and the effect of film-forming solution pH on the properties of intelligent films was investigated. The results of SEM, FTIR, XRD and TGA displayed that the hydrogen bond between CS and GSA was strong at strong acidic conditions (2.0-2.5), and it weakened at weak acidic conditions (3.0-4.5). Meanwhile, the hydrogen bond between PVA and GSA was negligible under strong acidic conditions, and it appeared under weak acidic conditions. Consequently, the films fabricated under weak acidic conditions displayed lower water solubility, lower water vapor permeability, and higher elongation at break. The tensile strength of films increased firstly and subsequently decreased with pH increasing, reaching a maximum value of 31.44 MPa at pH 3.5. Additionally, the films prepared at pH 2.5 and 4.0 showed the best color responsiveness to ammonia and acetic acid, respectively. Overall, the intelligent films prepared under variant pH have the potential to realize the goal of monitoring the freshness of different types of food, thereby expanding the application subject of anthocyanins-based intelligent films.

Effects of Microplastics on the Transport of Soil Dissolved Organic Matter in the Loess Plateau of China.

Microplastics (MPs) pollution and dissolved organic matter (DOM) affect soil quality and functions. However, the effect of MPs on DOM and underlying mechanisms have not been clarified, which poses a challenge to maintaining soil health. Under environmentally relevant conditions, we evaluated the major role of polypropylene particles at four micron-level sizes (20, 200, and 500 µm and mixed) in regulating changes in soil DOM content. We found that an increase in soil aeration by medium and high-intensity (>0.5%) MPs may reduce NH4+ leaching by accelerating soil nitrification. However, MPs have a positive effect on soil nutrient retention through the adsorption of PO43- (13.30-34.46%) and NH4+ (9.03-19.65%) and their leached dissolved organic carbon (MP-leached dissolved organic carbon, MP-DOC), thereby maintaining the dynamic balance of soil nutrients. The regulating ion (Ca2+) is also an important competitor in the MP-DOM adsorption system, and changes in its intensity are dynamically involved in the adsorption process. These findings can help predict the response of soil processes, especially nutrient cycling, to persistent anthropogenic stressors, improve risk management policies on MPs, and facilitate the protection of soil health and function, especially in future agricultural contexts.

Association of small-for-gestational-age status with mortality and morbidity in very preterm Chinese infants.

BACKGROUND: Very preterm infants born small for gestational age (SGA) are at risk for short- and long-term excess mortality and morbidity resulting from immaturity and deficient intrauterine growth. However, previous findings are inconclusive, and there is a paucity of contemporary data in Chinese population. OBJECTIVES: To evaluate the excess risks of mortality and morbidity independently associated with SGA birth in very preterm (before 32 weeks of gestation) Chinese infants. MATERIALS AND METHODS: The study population included all very preterm infants admitted to the neonatal intensive care units (NICUs) in our hospital and our medical treatment partner hospitals during a 6-year period. The SGA group consisted of 615 SGA infants, and 1230 appropriate-for-gestation-age (AGA) infants were matched with GA and sex as controls at a ratio of 2:1. The associations between SGA birth and outcomes (in-hospital mortality and morbidity) were evaluated by using multivariate logistic regression analysis after adjustment for potential confounders. The CRIBII score was used to indicate admission illness severity, acting as a covariate in the multivariate analysis. RESULTS: The SGA group was associated with increased risks of mortality [odds ratio (OR) 2.12; 95% CI: 1.27-3.54] and BPD [OR 1.95; 95% CI: 1.58-2.41] compared to the AGA group. No significant incidences of respiratory distress syndrome (RDS), severe retinopathy of prematurity (sROP), severe intraventricular hemorrhage (sIVH), and necrotizing enterocolitis (NEC) were observed in the SGA group. Further GA-stratified subgroup analysis showed SGA status exhibited certain patterns of effects on mortality and morbidity in different GA ranges. CONCLUSIONS: SGA status is associated with excess risks of neonatal mortality and BPD in very preterm infants, but the increased risks of mortality and morbidity are not homogeneous in different GA ranges. The contemporary data can help inform perinatal care decision-making and family counseling, particularly for very preterm SGA neonates.

Phosphogypsum/titanium gypsum coupling for enhanced biochar immobilization of lead: Mineralization reaction behavior and electron transfer effect.

The hazards caused by Pb pollution have received worldwide attention. Phosphogypsum (PG) and titanium gypsum (TG) have the disadvantage of limited adsorption capacity and poor dispersion when used as heavy metal adsorbents on their own. The excellent pore and electron transfer capacity of biochar makes it possible to combine with PG and TG to solidify/stabilize Pb2+. In this study, the mechanism of Pb2+ adsorption/immobilization by rice husk biochar (BC) combined with PG/TG was investigated in terms of both mineral formation and electron transfer rate. The removal rate of Pb2+ by BC composite PG (BC/PG-Pb) or TG (BC/TG-Pb) was as high as 97%-98%, an increase of 120.9% and 122.5% over BC. Adsorption kinetics and mineral precipitation results indicate that the main removal of Pb2+ from BC/PG-Pb and BC/TG-Pb is achieved by PG/TG induced Pb-sulfate and Pb-phosphate formation. The addition of PG/TG significantly enhances the formation of stable Pb-minerals on the biochar surface, with the proportion of non-bioaccessible forms exceeding 50%. The four-step extraction results confirm that P and F in PG/TG are key in facilitating the conversion of Pb minerals to pyromorphite. The rich pore structure of biochar not only disperses the easily agglomerated PG/TG onto the biochar surface, but also attracts Pb2+ for uniformly dispersed precipitation. Furthermore, the excellent electrical conductivity and smooth electron transfer channels of biochar facilitate the reaction rate of Pb2+ mineralization. Overall, the use of biochar in combination with PG/TG is a promising technology for the combination of solid waste resourceisation and Pb remediation.

Efficacy and Safety Evaluation of Scleral Cross-Linking Using Genipin in the Treatment of Juvenile Guinea Pigs with High Myopia.

Purpose: To investigate the efficacy and safety of scleral cross-linking (CXL) using Genipin in the treatment of juvenile guinea pigs with high myopia. Methods: Twenty-four 4-week-old tricolor guinea pigs with high myopia of diopter ≤ -6.0 DS in the right eye were randomly divided into two groups: Genipin CXL group and control group (n = 12 for each group). They received separately form-deprivation (FD) combined with sub-tenon injection, and the former was 0.5% Genipin solution, while the latter was 0.9% saline solution. Refractive error, axial length (AL), intraocular pressure (IOP), and structural and vasculature optic disc changes in optical coherence tomography (OCT) and OCT angiography (OCTA) were analyzed at baseline and at 3 weeks after injection. Results: Baseline parameters were similar between the two groups (P > 0.05). After 3 weeks of the intervention, the difference of AL between the two groups was statistically significant (t = -11.28, P < 0.001). Besides, IOP increased in both groups, and the changes of IOP between the two groups were statistically significant (t = 2.80, P = 0.01). The average cup-disc ratio (C/D) (t = 3.11, P = 0.006) and the vertical C/D (t = 2.96, P = 0.009) of OCT-related optic disc parameters in the Genipin CXL group increased, and the differences were statistically significant compared with the control group. Conclusion: The CXL method of sub-tenon injection of Genipin solution could effectively inhibit the progression of myopia in juvenile guinea pigs with highly myopic eyes combined with FD. The slightly elevated IOP and increased C/D of some fundus optic discs should be further assessed.

Rho-associated coiled-coil containing kinase inhibitor improves outcomes of direct-transfer slow-cooled bovine blastocysts.

Direct-transfer slow-cooling cryopreservation is a widely used method for bovine embryo cryopreservation. However, the transfer of cryopreserved embryos is associated with reduced pregnancy rates. Rho-associated coiled-coil containing kinase inhibitor (ROCKi) has shown promise in improving the viability of post-warmed vitrified bovine embryos. Our objective was to investigate the effects of ROCKi treatment prior to slow-cooling or after cryopreservation on embryo viability. In vitro produced bovine embryos (n = 571) were randomly assigned to one of five groups: No-cryopreservation control group (NC-C), C-C group were cryopreserved by slow-rate cooling without ROCKi at any point, R-C group were incubated with ROCKi for 2 h before cryopreservation, C-R group were not exposed to ROCKi prior to cryopreservation but were cultured with ROCKi after cryopreservation, and R-R group were exposed to ROCKi before and after cryopreservation. Treatment group was significantly associated with blastocoel re-expansion, hatching, and degeneration (P < 0.0001). Blastocoel re-expansion rates were lower (P < 0.05) in the C-C (75.2 ± 4.2%) and R-C (85.2 ± 4.7%) groups compared with the NC-C (99.0 ± 0.7%), C-R (94.7 ± 2.6%) and the R-R (94.5 ± 2.9%) groups. The median time to re-expansion was significantly slowest in the C-C group (650, 560-915 min), followed by the R-C group (538, 421-611 min), then the C-R and R-R groups were similar (291, 261-361 and 321, 271-371 min) and the NC-C group was the fastest (196, 161-230 min) (P < 0.05). Similarly, the post-thaw hatching rate was lower, and the median time to hatching slower in the C-C (58.1 ± 7.0%, 2,033, 1634-2820 min) and R-C (65.7 ± 6.9%, 1,853, 1494-2356 min) groups compared with the NC-C (81.7 ± 6.0%, 1,309, 1084-1514 min), C-R (77.2 ± 6.5%, 1,384, 1013-1754 min) and R-R (82.0 ± 5.3%, 1,209, 943-1424 min) groups. ROCKi supplementation after cryopreservation resulted in fewer degenerated embryos (C-R = 8.9 ± 2.8%, and R-R 7.1 ± 2.8%) compared to the C-C (26.8 ± 4.3%) and R-C (17.9 ± 5.7%) groups. Exposure to ROCKi both before cryopreservation and after-cryopreservation yielded the best outcomes, similar to NC-C control group without cryopreservation, and significantly better than the C-C control group without supplements. Exposure to ROCKi after cryopreservation demonstrated greater benefits compared to exposure before cryopreservation alone. These findings suggest that ROCKi can potentially enhance cryosurvival of bovine embryos.

Elevated Total Serum Immunoglobulin A Levels in Patients with Suspicion for Celiac Disease.

Patients with classic symptoms of celiac disease are often initially tested for serum tissue transglutaminase-immunoglobulin A (tTG-IgA) and total serum immunoglobulin A (IgA) levels concurrently, as IgA deficiency can lead to falsely low tTG-IgA. There are no guidelines for incidental findings of elevated total serum IgA when testing for celiac disease. In our study, we described the proportion of patients with suspicion of celiac disease who had elevated total serum IgA and the factors that may be associated with these findings. We studied the management of these patients with incidental findings of elevated total serum IgA to identify its clinical significance. To investigate, we performed a retrospective chart review of patients who underwent celiac disease serologic testing at a single clinic from January 2017 to June 2022. We reported further laboratory workup and follow-up for patients with incidental findings of elevated total serum IgA by board-certified immunologists. In our chart review, 848 patients were identified, 85 (10.0%) of whom were found to be negative for celiac disease but had elevated total serum IgA levels (median IgA 351 mg/dL, interquartile range 324-382). Out of 85 patients, 73 were further evaluated by immunologists, with 55 patients undergoing additional laboratory workup. None were diagnosed with specific immunologic conditions. Male sex was identified as associated with elevated total serum IgA findings, and constipation was found in a statistically significant greater frequency of patients with normal total serum IgA rather than elevated total serum IgA. To provide external validation of our findings, we created a second patient cohort within the Stanford Research Repository database. Out of 33,875 patients identified, a similarly high proportion of patients were negative for celiac disease but had elevated total serum IgA levels (9.3%, 3140 patients). In this separate patient cohort, male sex was also identified as being associated with elevated total serum IgA. Our study also provides preliminary evidence that patients with incidental findings of elevated total serum IgA may not need further management or workup, as these abnormalities may not be clinically relevant without other clinical suspicions.

Molecular characterization and transcriptional response to TiO2-GO nanomaterial exposure of two molt-related genes in the juvenile prawn, Macrobrachium rosenbergii.

In recent years, with the widespread use of TiO2-GO nanocomposite in industry, especially in the remediation of water environments, its toxic effects on aquatic organisms have received increasing attention. As molting is extremely important for crustaceans in their growth, in this study, we cloned the full-length cDNA sequences of two key genes related to molting, nuclear hormone receptor E75 (E75) and nuclear hormone receptor HR3 (HR3), in Macrobrachium rosenbergii, examined the gene expression profile, and investigated their toxicological effects on crustacean molting through nanomaterial exposure. The amino acid sequences for E75 and HR3 were respectively determined to encode 1138 and 363 acid residues. Sequence analysis showed that both E75 and HR3 contain a HOLI domain, with the E75 of M. rosenbergii being more closely related to the E75 of Palaemon carinicauda. These two genes were expressed at the highest levels in muscle, followed by hepatopancreas. The results showed that the expressions of E75 and HR3 in hepatopancreas and muscle tissues were significantly decreased after exposure to 0.1 mg/L of TiO2-GO composite nanoparticles (P < 0.05). This study will serve as a foundation for subsequent research into the evaluation of nanomaterial toxicity on crustacean species.

[Effect of continuous renal replacement therapy on plasma concentration, clinical efficacy and safety of colistin sulfate].

OBJECTIVE: To investigate the effects of continuous renal replacement therapy (CRRT) on plasma concentration, clinical efficacy and safety of colistin sulfate. METHODS: Clinical data of patients received with colistin sulfate were retrospectively analyzed from our group's previous clinical registration study, which was a prospective, multicenter observation study on the efficacy and pharmacokinetic characteristics of colistin sulfate in patients with severe infection in intensive care unit (ICU). According to whether patients received blood purification treatment, they were divided into CRRT group and non-CRRT group. Baseline data (gender, age, whether complicated with diabetes, chronic nervous system disease, etc), general data (infection of pathogens and sites, steady-state trough concentration, steady-state peak concentration, clinical efficacy, 28-day all-cause mortality, etc) and adverse event (renal injury, nervous system, skin pigmentation, etc) were collected from the two groups. RESULTS: A total of 90 patients were enrolled, including 22 patients in the CRRT group and 68 patients in the non-CRRT group. (1) There was no significant difference in gender, age, basic diseases, liver function, infection of pathogens and sites, colistin sulfate dose between the two groups. Compared with the non-CRRT group, the acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) were higher in the CRRT group [APACHE II: 21.77±8.26 vs. 18.01±6.34, P < 0.05; SOFA: 8.5 (7.8, 11.0) vs. 6.0 (4.0, 9.0), P < 0.01], serum creatinine level was higher [µmol/L: 162.0 (119.5, 210.5) vs. 72.0 (52.0, 117.0), P < 0.01]. (2) Plasma concentration: there was no significant difference in steady-state trough concentration between CRRT group and non-CRRT group (mg/L: 0.58±0.30 vs. 0.64±0.25, P = 0.328), nor was there significant difference in steady-state peak concentration (mg/L: 1.02±0.37 vs. 1.18±0.45, P = 0.133). (3) Clinical efficacy: there was no significant difference in clinical response rate between CRRT group and non-CRRT group [68.2% (15/22) vs. 80.9% (55/68), P = 0.213]. (4) Safety: acute kidney injury occurred in 2 patients (2.9%) in the non-CRRT group. No obvious neurological symptoms and skin pigmentation were found in the two groups. CONCLUSIONS: CRRT had little effect on the elimination of colistin sulfate. Routine blood concentration monitoring (TDM) is warranted in patients received with CRRT.

Combination with litchi procyanidins under PEF treatment alters the physicochemical and processing properties of inulin.

A novel alternative to prepare the inulin-procyanidin complex assisted by pulsed electric field (PEF) treatment was explored in this study. Results showed that the optimal condition of PEF treatment enhanced the adsorption rate of procyanidins to inulin from 78.56 to 103.46 µg/mg. Based on well fitted by Redlich-Peterson model and spectral analysis including UV and FT-IR, the interaction between inulin and procyanidin was evidenced to be dominated by hydrogen bonds. The DSC curve and the SEM spectrum displayed better stability of the PEF-treated inulin-procyanidin complex than the untreated complex. The PEF-treated complex had lower solubility but higher water-holding capacity than inulin, which exhibited stronger shear-thinning property and more stable flow behavior referring to rheological analysis. Furthermore, the gel formed from the PEF-treated complex possessed greater hardness, chewiness and viscosity, with no significant effects noted in terms of springiness, cohesiveness and resilience.

First Report of Enterobacter roggenkampii and E. cloacae complex sp. Caused Tomato Pith Necrosis in Guangdong Province, China.

Tomato (Solanum lycopersicum L.) is an important greenhouse and field-grown vegetable. During 2019 to 2021, a new bacterial pith necrosis broke out in tomato producing areas in China. The disease incidence rate in the field was approximately 10% to 30% in a few tomato planting areas of Guangdong province, and even 100% in Dianbai distinct, Maoming city. Diseased plants showed yellowing of the lower leaves, brown vascular tissues, and wilting along with brown necrotic spots and a large number of adventitious roots on the stem. Diseased plants were collected, and short fragments of the diseased stems were sterilized with 75% alcohol for 2 minutes, washed with sterile water twice, and stripped the cortex (Fang 1998). Dilutions of xylem specimen soaking solution were plated onto the TTC medium (peptone 10.0 g, acid hydrolyzed casein 1.0 g, glucose 5.0 g, agar 15.0 g, distilled water 1000 mL, 0.5% 2, 3, 5-triphenyltetrazolium chloride, pH7.0), and cultured at 28℃ for 24 h. Three pink single colonies (A2 from Guangzhou (113°21' E, 23°9' N), Guangdong, and K6, and K7 from Maoming (110°55' E, 21°25' N), Guangdong) were selected and purified. Strains A2, K6, and K7 were Gram-negative, motile, and showed white fluidal colonies with pink center on TTC medium, and white, round, and smooth-surface colonies on NA medium (peptone 10 g, beef extract 3 g, sodium chloride 5 g, agar 15 g, distilled water 1000 mL, pH7.0) at 28℃ for 24 h. Three strains could utilize citrate, sorbitol, lactose and arginine, and were negative for methylred reaction test, determination of phenylalanine amino acid deaminase, lysine decarboxylase, urease, soluble starch decomposition and gelatin liquefaction, whereas were positive for Voges-Proskauer test, which conformed to the characteristics of genus Enterobacter (Davin-Regli et al. 2019). To determine the species of the Enterobacter isolates, partial sequences 16S rDNA, gyrB, and rpoB of strain A2, K6, and K7 were amplified. The PCR products were purified, sequenced, and deposited to GenBank. The BLASTN analysis of 16S rDNA, rpoB and gyrB sequences showed strain A2 (MW785888, OL364948, OL364943) was 99.20%, 99.17% and 98.57% identity with E. roggenkampii DSM16690, respectively, strain K6 (MW785890, OL364950, OL364945) was 99.73%, 99.63%, 99.63% identity with E. cloacae complex sp. N13-01531, and strain K7 (MW785893, OL364951, OL364946) was 99.8%, 98.81%, 98.99% identity with the E. roggenkampii Ed-982 and Ek140. Nucleotide sequences of 3 strains were aligned using ClustalW program, and neighbor-joining method (NJ) was used in the construction of a phylogenetic tree using MEGA7 program. Phylogenetic trees based on gyrB sequence, rpoB sequence, and the concatenated sequence of 16S rDNA-rpoB-gyrB and rpoB-gyrB showed strain A2 and K7 were clustered to E. roggenkampii, strain K6 was clustered to E. cloacae complex sp. The roots of tomato material 'Moneymaker' at stage of 4-5 true leaves were cut and irrigated 10 mL bacterial suspension (OD600=0.6) of strains A2, K6, and K7, respectively. As a control, the tomato roots were treated with 10 mL sterile water. All plants were incubated at 30°C. The experiments were conducted with 20 tomato seedlings for each tested strain and control, and repeated twice. All plants inoculated showed yellowing in the lower leaves 6-7 days after inoculation (DAI), subsequently the stems of some plants were rotten, along with bacterial pus in the internodes. The plants wilted, and stems were hollow 20 DAI, which is similar to the field symptoms. No symptoms were observed in control plants. Strains were successfully reisolated from wilting plants, and identified as A2, K6, and K7, respectively, based on gyrB sequence analysis, fulfilling Koch's postulates. Zhou et al. (2021) reported that E. roggenkampii caused bacterial wilt of mulberry in Guangxi, China. Chen et al. (2021) reported E. asburiae caused tomatoes pith necrosis in Fujian and Zhejiang, China. To our knowledge, this is the first report of E. roggenkampii and E. cloacae complex sp. causing bacterial pith necrosis of tomato. Further research would focus on exploring the pathogenic mechanism of the pathogen, and providing reference of controlling the disease.