The prevention effect of Limosilactobacillus reuteri on acute kidney injury by regulating gut microbiota.

Acute kidney injury (AKI) has considerably high morbidity and mortality but we do not have proper treatment for it. There is an urgent need to develop new prevention or treatment methods. Gut microbiota has a close connection with renal diseases and has become the new therapy target for AKI. In this study, we found the oral administration of the probiotic Limosilactobacillus reuteri had a prevention effect on the AKI induced by lipopolysaccharide (LPS). It reduced serum concentration of creatinine and urea nitrogen and protected the renal cells from necrosis and apoptosis. Meanwhile, L. reuteri improved the gut barrier function, which is destroyed in AKI, and modulated the gut microbiota and relevant metabolites. Compared with the LPS group, L. reuteri increased the proportion of Proteobacteria and reduced the proportion of Firmicutes, changing the overall structure of the gut microbiota. It also influenced the fecal metabolites and changed the metabolite pathways, such as tyrosine metabolism, pentose and glucuronate interconversions, galactose metabolism, purine metabolism, and insulin resistance. These results showed that L. reuteri is a potential therapy for AKI as it helps in sustaining the gut barrier integrity and modulating gut microbiota and related metabolites.

Effects of high moisture ear corn on production performance, milk fatty acid composition, serum antioxidant status, and immunity in primiparous dairy cows.

Objective: This study evaluated the effects of high moisture ear corn (HMEC) on production performance, milk fatty acid composition, serum antioxidant status, and immunity in primiparous dairy cows. Methods: A total of 45 healthy primiparous Holstein cows (36.50±4.30 kg of milk/day, 201±9.00 lactating days in milk) were sorted into 3 groups: control group (CG, n = 15), 50% HMEC (replacing 50% steam-flaked corn with HMEC, n = 15), and 100% HMEC (replacing steam-flaked corn with HMEC, n = 15) on an equal dry matter (DM) basis. The study consisted of adaptation period of 14 days, followed by a formal period of 60 days. Feed intake and milk yield were recorded daily. Milk and blood samples were collected on 1, 30, and 60 d of the experimental period. Results: The 50% HMEC group and 100% HMEC group significantly increased (p<0.05) milk yield and dry matter intake (DMI) in dairy cows compared to the control group (CG). The 100% HMEC group showed an increase (p<0.05) in 4% fat-corrected milk (4% FCM). Both the 50% HMEC group and 100% HMEC group exhibited significant decreases (p<0.05) in the content of C10:0, C12:0, and C14:0 fatty acids, along with a significant increase (p<0.05) in cis-9C18:1 content. The saturated fatty acid (SFA) content was significantly lower (p<0.05) in the 50% HMEC and 100% HMEC groups than that of CG. Conversely, the monounsaturated fatty acid (MUFA) content was higher (p<0.05) in the 50% HMEC and 100% HMEC groups than that in CG. Notably, the 100% HMEC group significantly increased (p<0.05) the serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) content, while also decreasing the serum malondialdehyde (MDA) content (p<0.05). Moreover, the 100% HMEC group significantly increased (p<0.05) the content of immunoglobulin G (IgG) and immunoglobulin M (IgM). Conclusion: High moisture ear corn could improve production performance and milk fatty acid levels and enhance immunity and antioxidant capacity in dairy cows. These results lay the foundation for the wider application of HMEC in ruminant animal diets.

LC-MS/MS methods for simultaneous determination of youkenafil and its metabolite M1 in human seminal plasma and plasma: Application to evaluate the acute effect of youkenafil on semen quality and its pharmacokinetics in human.

Youkenafil is a novel Phosphodiesterase type 5 inhibitor used for treating erectile dysfunction. N-desethyl compound of youkenafil (M1) is its main active metabolite. In this study, two methods were developed and validated for the simultaneous determination of youkenafil and M1 by HPLC-MS/MS in human matrices including seminal plasma and plasma, in which the multiple reaction monitoring and electrospray ionization in positive mode were adopted, and the deuterated youkenafil (youkenafil-d5) was selected as the internal standard. The collected semen sample was kept at room temperature for approximately 30 min until fully liquefied. The volume of the liquefied semen was measured and then divided into two parts. One part was centrifuged to obtain the seminal plasma for the content detection of youkenafil and M1, while the other part was used for routine semen analysis. The chromatographic separation was accomplished with the column of Poroshell 120 EC-C18 (5 × 2.1 mm, 2.7 µm, Agilent). Protein precipitation with methanol was used for the pretreatment of seminal plasma and plasma. The intra-run and inter-run precisions were less than 6.4 % (relative standard deviation) and accuracies were all within -4.7 %-6.8 % (relative error) in both matrices. All other validated bioanalytical parameters were within the acceptance criteria set by the FDA. The methods were successfully applied to different clinical studies of youkenafil. In the clinical study of the acute effect of youkenafil on semen quality in healthy males, the content of youkenafil in seminal plasma was extremely low. Concentrations of youkenafil and M1 in seminal plasma were lower than those in plasma, at 20.7 % and 4.49 % of the plasma concentration, respectively. There was no significant acute effect of youkenafil on semen quality. In the pharmacokinetic study of youkenafil after single dose-escalation administration, the exposure to youkenafil and M1 was non-linear with the dose in the range of 100-400 mg.

Neoadjuvant chemo-immunotherapy with camrelizumab plus nab-paclitaxel and cisplatin in resectable locally advanced squamous cell carcinoma of the head and neck: a pilot phase II trial.

Neoadjuvant chemoimmunotherapy has emerged as a potential treatment option for resectable head and neck squamous cell carcinoma (HNSCC). In this single-arm phase II trial (NCT04826679), patients with resectable locally advanced HNSCC (T2‒T4, N0‒N3b, M0) received neoadjuvant chemoimmunotherapy with camrelizumab (200 mg), nab-paclitaxel (260 mg/m2), and cisplatin (60 mg/m2) intravenously on day one of each three-week cycle for three cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included pathologic complete response (pCR), major pathologic response (MPR), two-year progression-free survival rate, two-year overall survival rate, and toxicities. Here, we report the perioperative outcomes; survival outcomes were not mature at the time of data analysis. Between April 19, 2021 and March 17, 2022, 48 patients were enrolled and received neoadjuvant therapy, 27 of whom proceeded to surgical resection and remaining 21 received non-surgical therapy. The ORR was 89.6% (95% CI: 80.9, 98.2) among 48 patients who completed neoadjuvant therapy. Of the 27 patients who underwent surgery, 17 (63.0%, 95% CI: 44.7, 81.2) achieved a MPR or pCR, with a pCR rate of 55.6% (95% CI: 36.8, 74.3). Treatment-related adverse events of grade 3 or 4 occurred in two patients. This study meets the primary endpoint showing potential efficacy of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin, with an acceptable safety profile, in patients with resectable locally advanced HNSCC.

Global prevalence of restless legs syndrome among hemodialysis patients: A systematic review and meta-analysis.

OBJECTIVES: Restless legs syndrome (RLS) is a common complaint in patients undergoing hemodialysis (HD). Despite the fact that the estimated prevalence of RLS among HD patients is widely reported, these results varied significantly in the relevant literature. Due to this limitation, the aim of this study was to determine the global prevalence of RLS among HD patients. METHODS: This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 statement. We searched the electronic databases: Cochrane Library, PubMed, Embase, Web of Science, Scopus, Cumulative Index to Nursing and Allied Health Literature, China Knowledge Resource Integrated Database, Wanfang Database, Chinese Biomedical Database, and Weipu Database. A random effects model was employed to calculate pooled prevalence rates. RESULTS: The global pooled prevalence of RLS in HD patients was 27.2% (95% CI: 24.8-29.7). Stratified analyses demonstrated that included studies with sample size <100 had the highest pooled prevalence of RLS. The prevalence of RLS using clinical interviews and questionnaires was 28.7% (95% CI: 25.2-32.2) and 25.9% (95% CI: 22.8-29.1), respectively. RLS prevalence is higher in females (29.7%, 95% CI: 26.2-33.2) HD patients than in males (23.5%, 95% CI: 20.9-26.0), and the African region has the highest prevalence in the world when the diagnostic criteria were restricted to the 2003 version of International RLS Study Group criteria, the prevalence of RLS was highest (28.9%, 95% CI: 25.9-31.9). CONCLUSION: Our results revealed a high RLS prevalence in HD patients worldwide. However, the prevalence of RLS among HD patients varied significantly based on sample size, data collection method, gender, diagnostic criteria, and geographical region.

Blindness in Right Eyes after Enema: A Case of Klebsiella pneumoniae-Related Invasive Liver Abscess Syndrome with Endophthalmitis-Caused Blindness as the First Symptom.

We report a case of Klebsiella pneumoniae invasive liver abscess syndrome (KPILAS) with endophthalmitis-caused blindness as the first symptom after enema. The patient had diabetes, and his blood glucose was poorly controlled. She developed hematuria after four enemas for cosmetic purposes and later became blind. The eye discharge was cultured, which revealed a Klebsiella pneumoniae infection. B ultrasound did not show liver lesions, but computed tomography exhibited abscesses in the right lobe of the liver. Magnetic resonance imaging of the head indicated abscesses. These confirmed the diagnosis of invasive liver abscess syndrome. The patient was given ophthalmic and systemic anti-infection treatments, and her condition was effectively controlled. Unfortunately, the diseased eye still needed to be removed. This case underlines the necessity of avoiding unnecessary risky procedures (such as enemas) in vulnerable populations, the importance of early detection of invasive liver abscess syndrome, and the advantage of computed tomography in detecting liver abscesses.

Sodium alginate/sodium lignosulfonate hydrogel based on inert Ca2+ activation for water conservation and growth promotion.

Soil degradation has become a major global problem owing to the rapid development of agriculture. The problems of soil drought and decreased soil fertility caused by soil degradation severely affect the development of the agricultural and forestry industries. In this study, we designed sodium alginate (SA)/sodium lignosulfonate (SLS) hydrogel based on the activation and crosslinking of inert Ca2+. CaCO3 and SA were mixed, and then, inert Ca2+ was activated to prepare a gel with a stable structure and a uniform interior and exterior. The crosslinking activated by inert Ca2+ enhanced the stability of the hydrogel, and the optimal swelling rate of the hydrogel reached 28.91 g/g, thereby effectively improving the water-holding capacity of the soil (77.6-108.83 g/kg). SLS was degraded into humic acid (HA) and gradually released, demonstrating a positive growth-promoting effect in plant growth experiments. The SA/SLS hydrogel can be used for soil water retention and mitigation to significantly decrease the water loss rate of soil. This study will assist in addressing soil drought and fertility loss.

Flexible Cages Enable Robust Supramolecular Elastomers.

Advances in modern industrial technology continue to place stricter demands on engineering polymeric materials, but simultaneously possessing superior strength and toughness remains a daunting challenge. Herein, a pioneering flexible cage-reinforced supramolecular elastomer (CSE) is reported that exhibits superb robustness, tear resistance, anti-fatigue, and shape memory properties, achieved by innovatively introducing organic imide cages (OICs) into supramolecular networks. Intriguingly, extremely small amounts of OICs make the elastomer stronger, significantly improving mechanical strength (85.0 MPa; ≈10-fold increase) and toughness (418.4 MJ m-3; ≈7-fold increase). Significantly, the cooperative effect of gradient hydrogen bonds and OICs is experimentally and theoretically demonstrated as flexible nodes, enabling more robust supramolecular networks. In short, the proposed strengthening strategy of adding flexible cages effectively balances the inherent conflict between material strength and toughness, and the prepared CSEs are anticipated to be served in large-scale devices such as TBMs in the future.

Properties of Mixed Crystal Coprecipitation Substances of Ammonium Nitrate and Potassium Perchlorate Prepared by the Evaporative Solvent Method.

Ammonium perchlorate (AP) has been widely used as an oxidizer in propellants and military mixed explosives in recent years. However, its high characteristic signal, environmental pollution, and poor detonation performance have prompted the industry to seek alternatives to AP. Ammonium nitrate (AN) is a suitable substitute due to its low characteristic signal, lack of pollution, and excellent detonation performance. However, its room-temperature phase transition and hygroscopicity affect its practical use. In this work, we prepared mixed crystal coprecipitation (MCC) materials of AN and potassium perchlorate (KP) using the evaporative solvent method. The characterization of AN/KP MCCs was carried out by combining TG-DSC, XRD, FT-IR, and SEM analysis, revealing that the formation of MCCs by AN and KP is due to ion exchange between the two components. AN/KP MCCs not only solve the problem of room-temperature phase transition in AN but also reduce its hygroscopicity. Furthermore, AN/KP MCCs have mechanical sensitivity, explosive performance, and specific impulse similar to pure AN, but compared to AN, AN/KP MCCs have higher density, effective oxygen content, and thermal stability. Compared with existing oxidizers AN, AP, and KP, AN/KP MCCs with high density, low sensitivity, high oxygen content, and high safety have obvious advantages and have good prospects in the application of oxidizers in solid propellants and military mixed explosives.

Insight into bacterial and archaeal community structure of Suaeda altissima and Suaeda dendroides rhizosphere in response to different salinity level.

IMPORTANCE: Suaeda play an important ecological role in reclamation and improvement of agricultural saline soil due to strong salt tolerance. At present, research on Suaeda salt tolerance mainly focuses on the physiological and molecular regulation. However, the important role played by microbial communities in the high-salinity tolerance of Suaeda is poorly studied. Our findings have important implications for understanding the distribution patterns and the driving mechanisms of different Suaeda species and soil salinity levels. In addition, we explored the key microorganisms that played an important ecological role in Suaeda rhizosphere. We provide a basis for biological improvement and ecological restoration of salinity-affected areas.

Simultaneous determination of tipiracil, trifluridine and its metabolite 5-trifluoromethyluracil in human plasma using segmented polarity LC-MS/MS: A fully validated assay with clinical application.

Trifluridine (FTD) and tipiracil (TPI) hydrochloride tablets (TAS-102) were used for the treatment of patients with metastatic rectal cancer that was resistant to conventional chemotherapy drugs. In this study, a rapid and sensitive liquid chromatography-tandem mass spectrometry method was developed and fully validated for the simultaneous determination of TPI, FTD, and the metabolite 5-trifluoromethyluracil (FTY) of FTD in human plasma. The plasma samples were prepared by protein precipitation. The chromatography separation was performed using ACE Excel 3 AQ (100 × 2.1 mm i.d., 1.7 µm, ACE, England) column protected by a security guard cartridge (4.0 × 2.0 mm i.d., 5 µm, Phenomenex, USA) with a gradient elution of 0.05% acetic acid in water and methanol at a flow rate of 0.35 mL/min. The MS/MS analysis was performed by using multiple reaction monitoring with the segmented polarity (positive for TPI: m/z 243.1→183.0, and negative for FTD: m/z 295.1→252.0 and FTY: m/z 178.9→158.9) electrospray ionization mode. The segmented polarity mode was designed to achieve two advantages: better sensitivity and simultaneous determination of the analytes with different ion polarities. The calibration ranges were as follows: 1.00-250 ng/ for TPI, 8.00-8000 ng/mL for FTD and 5.00-1250 ng/mL for FTY. The selectivity, accuracy, precision, matrix effect, recovery, carryover, dilution integrity and stability test results meet ICH acceptance criteria. The method was evaluated using the RGB model and successfully applied to a clinical study in patients with solid tumors. For TPI, FTD and FTY, the maximum plasma concentration was 137-147 ng/mL, 6160-6240 ng/mL and 724-725 ng/mL, respectively; the plasma elimination half-life was 1.69-1.78 h, 1.70 h, and 3.09-3.14 h, respectively, after an oral administration of 60 mg TAS-102.

Metabolic engineering of glycolysis in Escherichia coli for efficient production of patchoulol and τ-cadinol.

Glucose metabolism suppresses the microbial synthesis of sesquiterpenes with a syndrome of "too much of a good thing can be bad". Here, patchoulol production in Escherichia coli was increased 2.02 times by engineering patchoulol synthase to obtain an initial strain. Knocking out the synthetic pathway for cyclic adenosine monophosphate relieved glucose repression and improved patchoulol titer and yield by 27.7 % and 43.1 %, respectively. A glycolysis regulation device mediated by pyruvate sensing was constructed which effectively alleviated overflow metabolism in a high-glucose environment with 10.2 % greater patchoulol titer in strain 070QA. Without fine-tuning the glucose-feeding rate, patchoulol titer further increased to 1675.1 mg/L in a 5-L bioreactor experiment, which was the highest level reported in E. coli. Using strain 070QA as a chassis, the τ-cadinol titer reached 15.2 g/L, representing the first report for microbial production of τ-cadinol. These findings will aid in the industrial production of sesquiterpene.

Effect of additives and moisture on the fermentation quality and bacterial community of high moisture ear corn.

Maize (Zea mays L) is one of the most widely cultivated crops used as energy feeds. The aim of this study was to evaluate the effects of two lactic acid bacteria additives on the fermentation quality and bacterial community of high moisture ear corn (HMEC) silage at different moisture levels. The study utilized corn kernels and cobs harvested at the stage of complete ripeness as the primary material. The cob was crushed and divided into three treatment groups: an untreated control group (CK), a group treated with a mixture of Lactobacillus plantarum and Lactobacillus brucei (TQ), or a group treated with a mixture of Lactococcus lactis and Lactobacillus brucei (KT). Moisture contents were adjusted to 37.5% (L), 42.5% (M) or 47.5% (H) and then silaged for 180 days. Compared to CK, TQ, and KT elevated the dry matter, crude protein, starch, lactic and acetic acid content of HMEC and reduced the pH, neutral detergent fiber, acid detergent fiber and ammonia nitrogen content (p < 0.05). Even though both additives improved the bacterial community structure after fermentation, KT experienced the greater enhancement. At a phylum and genus level, KT had the higher relative abundance of Firmicutes and Lactobacillus, respectively. Compared with the group of 37.5% (L) moisture content, the 42.5% (M) and 47.5% moisture content (H) group increased lactic acid, acetic acid and ammonia nitrogen concentrations and reduced the pH value (p < 0.05). In conclusion, the addition of TQ and KT at the appropriate moisture content might be helpful for producing high-quality HMEC. Among the three moisture contents, 42.5% (M) moisture content provides the best silage qualities.

CD147: an integral and potential molecule to abrogate hallmarks of cancer.

CD147 also known as EMMPRIN, basigin, and HAb18G, is a single-chain type I transmembrane protein shown to be overexpressed in aggressive human cancers of CNS, head and neck, breasts, lungs, gastrointestinal, genitourinary, skin, hematological, and musculoskeletal. In these malignancies, the molecule is integral to the diverse but complimentary hallmarks of cancer: it is pivotal in cancerous proliferative signaling, growth propagation, cellular survival, replicative immortality, angiogenesis, metabolic reprogramming, immune evasion, invasion, and metastasis. CD147 also has regulatory functions in cancer-enabling characteristics such as DNA damage response (DDR) and immune evasion. These neoplastic functions of CD147 are executed through numerous and sometimes overlapping molecular pathways: it transduces signals from upstream molecules or ligands such as cyclophilin A (CyPA), CD98, and S100A9; activates a repertoire of downstream molecules and pathways including matrix metalloproteinases (MMPs)-2,3,9, hypoxia-inducible factors (HIF)-1/2α, PI3K/Akt/mTOR/HIF-1α, and ATM/ATR/p53; and also functions as an indispensable chaperone or regulator to monocarboxylate, fatty acid, and amino acid transporters. Interestingly, induced loss of functions to CD147 prevents and reverses the acquired hallmarks of cancer in neoplastic diseases. Silencing of Cd147 also alleviates known resistance to chemoradiotherapy exhibited by malignant tumors like carcinomas of the breast, lung, pancreas, liver, gastric, colon, ovary, cervix, prostate, urinary bladder, glioblastoma, and melanoma. Targeting CD147 antigen in chimeric and induced-chimeric antigen T cell or antibody therapies is also shown to be safer and more effective. Moreover, incorporating anti-CD147 monoclonal antibodies in chemoradiotherapy, oncolytic viral therapy, and oncolytic virus-based-gene therapies increases effectiveness and reduces on and off-target toxicity. This study advocates the expedition and expansion by further exploiting the evidence acquired from the experimental studies that modulate CD147 functions in hallmarks of cancer and cancer-enabling features and strive to translate them into clinical practice to alleviate the emergency and propagation of cancer, as well as the associated clinical and social consequences.

Rapid Polyolefin Hydrogenolysis by a Single-Site Organo-Tantalum Catalyst on a Super-Acidic Support: Structure and Mechanism.

The novel electrophilic organo-tantalum catalyst AlS/TaNpx (1) (Np=neopentyl) is prepared by chemisorption of the alkylidene Np3 Ta=CHt Bu onto highly Brønsted acidic sulfated alumina (AlS). The proposed catalyst structure is supported by EXAFS, XANES, ICP, DRIFTS, elemental analysis, and SSNMR measurements and is in good agreement with DFT analysis. Catalyst 1 is highly effective for the hydrogenolysis of diverse linear and branched hydrocarbons, ranging from C2 to polyolefins. To the best of our knowledge, 1 exhibits one of the highest polyolefin hydrogenolysis activities (9,800 (CH2 units) ⋅ mol(Ta)-1 ⋅ h-1 at 200 °C/17 atm H2 ) reported to date in the peer-reviewed literature. Unlike the AlS/ZrNp2 analog, the Ta catalyst is more thermally stable and offers multiple potential C-C bond activation pathways. For hydrogenolysis, AlS/TaNpx is effective for a wide variety of pre- and post-consumer polyolefin plastics and is not significantly deactivated by standard polyolefin additives at typical industrial concentrations.

Expectation-maximization vector approximate message passing-based frequency-domain turbo equalization for underwater acoustic communications.

Channel equalization plays a crucial role in single-carrier underwater acoustic (UWA) communications. Recently, a frequency-domain turbo equalization (FDTE) scheme enabled by the vector approximate message passing (VAMP) algorithm, was proposed, and it outperformed classic linear minimum mean square error FDTE at acceptable complexity cost. The operation of the VAMP-FDTE requires knowledge of noise power, which is predetermined before the equalization starts. In practice, however, it is difficult to obtain prior knowledge of noise power due to factors of unknown channel estimation errors and dynamic underwater environments. Motivated by this fact, we propose an enhanced VAMP-FDTE scheme, which learns the noise power knowledge during the equalization process via the expectation-maximization (EM) algorithm. The EM-based noise power estimation makes use of intermediate results of the VAMP-FDTE and, thus, only incurs a small extra computational overhead. The improved VAMP-FDTE, named EM-VAMP-FDTE, was tested by experimental data collected in shallow-sea horizontal UWA communication trials with MIMO configuration. It showed better performance than the existing VAMP-FDTE scheme, attributed to the online noise power learning.

Design and Application of Memristive Balanced Ternary Univariate Logic Circuit.

This paper proposes a unique memristor-based design scheme for a balanced ternary digital logic circuit. First, a design method of a single-variable logic function circuit is proposed. Then, by combining with a balanced ternary multiplexer, some common application-type combinational logic circuits are proposed, including a balanced ternary half adder, multiplier and numerical comparator. The above circuits are all simulated and verified in LTSpice, which demonstrate the feasibility of the proposed scheme.

Coordination-Induced Conformational Control Enables Highly Luminescent Metallo-Cages.

In recent years, luminescent materials have received a great deal of attention due to their wide range of applications. However, exploring a simple solution to overcome the fluorescence quenching resulting from the aggregation of conventional organic fluorophores remains a valuable area of investigation. In this study, we successfully constructed two metallo-cages, namely, SA and SB, through coordination-driven self-assemblies of the triphenylamine (TPA)-based donor L with different diplatinum(II) acceptors LA and LB, respectively. These metallo-cages take advantage of their steric nature and curved conformation to more effectively limit the free rotation of the benzene ring and hinder π-π stacking in the solid state, which successfully inhibited fluorescence quenching and realizing highly efficient luminescent properties. Therefore, this work offers a new design strategy for preparing materials with excellent luminescent properties.