Rapid and accurate detection of cinnamon oil adulteration in perilla leaf oil using atmospheric solids analysis probe-mass spectrometry.

Perilla leaf oil (PLO) is a global premium vegetable oil with abundant nutrients and substantial economic value, rendering it susceptible to potential adulteration by unscrupulous entrepreneurs. The addition of cinnamon oil (CO) is one of the main adulteration avenues for illegal PLOs. In this study, new and real-time ambient mass spectrometric methods were developed to detect CO adulteration in PLO. First, atmospheric solids analysis probe tandem mass spectrometry combined with principal component analysis and principal component analysis-linear discriminant analysis was employed to differentiate between authentic and adulterated PLO. Then, a spectral library was established for the instantaneous matching of cinnamaldehyde in the samples. Finally, the results were verified using the SRM mode of ASAP-MS/MS. Within 3 min, the three methods successfully identified CO adulteration in PLO at concentrations as low as 5% v/v with 100% accuracy. The proposed strategy was successfully applied to the fraud detection of CO in PLO.

Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery.

JOURNAL/nrgr/04.03/01300535-202501000-00030/figure1/v/2024-05-14T021156Z/r/image-tiff Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery. Our previous in vitro study demonstrated that exosomes/small extracellular vesicles (sEVs) isolated from cerebral endothelial cells (CEC-sEVs) of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a (miR-27a) is an elevated miRNA in ischemic CEC-sEVs. In the present study, we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a (27a-sEVs) further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs. 27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector. Small EVs isolated from CECs transfected with a scramble vector (Scra-sEVs) were used as a control. Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs. An array of behavior assays was used to measure neurological function. Compared with treatment of ischemic stroke with Scra-sEVs, treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side, and significantly improved neurological outcomes. In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth. Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone, while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a, and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone. Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs. Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes. Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke.

JOURNAL/nrgr/04.03/01300535-202503000-00029/figure1/v/2024-06-17T092413Z/r/image-tiff It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke. Indeed, previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue. Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke, but its specific role and mechanism are currently unclear. To simulate stroke in vivo, a middle cerebral artery occlusion rat model was established, with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke. We found that in the early stage (within 24 hours) of ischemic stroke, neutrophils produced a large amount of hypochlorous acid, while in the recovery phase (10 days after stroke), microglia were activated and produced a small amount of hypochlorous acid. Further, in acute stroke in rats, hypochlorous acid production was prevented using a hypochlorous acid scavenger, taurine, or myeloperoxidase inhibitor, 4-aminobenzoic acid hydrazide. Our results showed that high levels of hypochlorous acid (200 µM) induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation. However, in the recovery phase of the middle cerebral artery occlusion model, a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes. This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury. Lower levels of hypochlorous acid (5 and 100 µM) promoted nuclear translocation of ß-catenin. By transfection of single-site mutation plasmids, we found that hypochlorous acid induced chlorination of the ß-catenin tyrosine 30 residue, which promoted nuclear translocation. Altogether, our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

Therapeutic potential of targeting protein tyrosine phosphatases in liver diseases.

Protein tyrosine phosphorylation is a post-translational modification that regulates protein structure to modulate demic organisms' homeostasis and function. This physiological process is regulated by two enzyme families, protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). As an important regulator of protein function, PTPs are indispensable for maintaining cell intrinsic physiology in different systems, as well as liver physiological and pathological processes. Dysregulation of PTPs has been implicated in multiple liver-related diseases, including chronic liver diseases (CLDs), hepatocellular carcinoma (HCC), and liver injury, and several PTPs are being studied as drug therapeutic targets. Therefore, given the regulatory role of PTPs in diverse liver diseases, a collated review of their function and mechanism is necessary. Moreover, based on the current research status of targeted therapy, we emphasize the inclusion of several PTP members that are clinically significant in the development and progression of liver diseases. As an emerging breakthrough direction in the treatment of liver diseases, this review summarizes the research status of PTP-targeting compounds in liver diseases to illustrate their potential in clinical treatment. Overall, this review aims to support the development of novel PTP-based treatment pathways for liver diseases.

Sensitivity analysis of slope stability based on eXtreme gradient boosting and SHapley Additive exPlanations: An exploratory study.

Slope instability through can cause catastrophic consequences, so slope stability analysis has been a key topic in the field of geotechnical engineering. Traditional analysis methods have shortcomings such as high operational difficulty and time-consuming, for this reason many researchers have carried out slope stability analysis based on AI. However, the current relevant studies only judged the importance of each factor and did not specifically quantify the correlation between factors and slope stability. For this purpose, this paper carried out a sensitivity analysis based on the XGBoost and SHAP. The sensitivity analysis results of SHAP were also validated using GeoStudio software. The selected influence factors included slope height ( H ), slope angle ( ß ), unit weight ( γ ), cohesion ( c ), angle of internal friction ( φ ) and pore water pressure coefficient ( r u ). The results showed that c and γ were the most and least important influential parameters, respectively. GeoStudio simulation results showed a negative correlation between γ , ß , H , r u and slope stability, while a positive correlation between c , φ and slope stability. However, for real data, SHAP misjudged the correlation between γ and slope stability. Because current AI lacked common sense knowledge and, leading SHAP unable to effectively explain the real mechanism of slope instability. For this reason, this paper overcame this challenge based on the priori data-driven approach. The method provided more reliable and accurate interpretation of the results than a real sample, especially with limited or low-quality data. In addition, the results of this method showed that the critical values of c , φ , ß , H , and r u in slope destabilization are 18 Kpa, 28°, 32°, 30 m, and 0.28, respectively. These results were closer to GeoStudio simulations than real samples.

Unloading and successful treatment with bioresorbable stents during percutaneous coronary intervention: A case report.

BACKGROUND: With the development of percutaneous coronary intervention (PCI), the number of interventional procedures without implantation, such as bioresorbable stents (BRS) and drug-coated balloons, has increased annually. Metal drug-eluting stent unloading is one of the most common clinical complications. Comparatively, BRS detachment is more concealed and harmful, but has yet to be reported in clinical research. In this study, we report a case of BRS unloading and successful rescue. CASE SUMMARY: This is a case of a 59-year-old male with the following medical history: "Type 2 diabetes mellitus" for 2 years, maintained with metformin extended-release tablets, 1 g PO BID; "hypertension" for 20 years, with long-term use of metoprolol sustained-release tablets, 47.5 mg PO QD; "hyperlipidemia" for 20 years, without regular medication. He was admitted to the emergency department of our hospital due to intermittent chest pain lasting 18 hours, on February 20, 2022 at 15: 35. Electrocardiogram results showed sinus rhythm, ST-segment elevation in leads I and avL, and poor R-wave progression in leads V1-3. High-sensitivity troponin I level was 4.59 ng/mL, indicating an acute high lateral wall myocardial infarction. The patient's family requested treatment with BRS, without implantation. During PCI, the BRS became unloaded but was successfully rescued. The patient was followed up for 2 years; he had no episodes of angina pectoris and was in generally good condition. CONCLUSION: We describe a case of a 59-year-old male experienced BRS unloading and successful rescue. By analyzing images, the causes of BRS unloading and the treatment plan are discussed to provide insights for BRS release operations. We discuss preventive measures for BRS unloading.

A self-fused peptide-loaded hydrogel with injectability and tissue-adhesiveness for preventing postoperative peritoneal adhesions.

Peritoneal adhesions commonly occur following abdominal or pelvic surgery and can cause serious complications. Currently, physical barriers are the primary approach used in clinical practice to prevent adhesion, although their effectiveness is frequently inadequate. In this study, we developed an injectable peptide-loaded hydrogel with multiple functions, including self-fusion, tissue-adhesiveness, anti-inflammation, anti-cell adhesion and anti-angiogenesis. To assess the effectiveness of these hydrogels, which are stabilized by dynamic imine bonds and acetal connections, in preventing postoperative abdominal adhesions, we utilized both a rat abdominal adhesion model and a rat model simulating repeated-injury adhesions. In comparison to the commercially available HA hydrogel, as-prepared hydrogels exhibited significant reductions in inflammation, fibrosis, and angiogenesis, leading to an obvious decrease in peritoneal adhesions. Moreover, this peptide-loaded hydrogel demonstrated an ideal degradation time, maintaining an in vivo viability for about 10 days. We believe this peptide-loaded hydrogel presents a promising solution for the challenging clinical issue of postoperative abdominal adhesions.

Advances in Mussel Adhesion Proteins and Mussel-Inspired Material Electrospun Nanofibers for Their Application in Wound Repair.

Mussel refers to a marine organism with strong adhesive properties, and it secretes mussel adhesion protein (MAP). The most vital feature of MAP is the abundance of the 3,4-dihydroxyphenylalanine (DOPA) group and lysine, which have antimicrobial, anti-inflammatory, antioxidant, and cell adhesion-promoting properties and can accelerate wound healing. Polydopamine (PDA) is currently the most widely used mussel-inspired material characterized by good adhesion, biocompatibility, and biodegradability. It can mediate various interactions to form functional coatings on cell-material surfaces. Nanofibers based on MAP and mussel-inspired materials have been exerting a vital role in wound repair, while there is no comprehensive review presenting them. This Review introduces the structure of MAPs and their adhesion mechanisms and mussel-inspired materials. Second, it introduces the functionalized modification of MAPs and their inspired materials in electrospun nanofibers and application in wound repair. Finally, the future development direction and coping strategies of MAP and mussel-inspired materials are discussed. Moreover, this Review can offer novel strategies for the application of nanofibers in wound repair and bring about new breakthroughs and innovations in tissue engineering and regenerative medicine.

Targeting APT2 improves MAVS palmitoylation and antiviral innate immunity.

Innate immunity serves as the primary defense against viral and microbial infections in humans. The precise influence of cellular metabolites, especially fatty acids, on antiviral innate immunity remains largely elusive. Here, through screening a metabolite library, palmitic acid (PA) has been identified as a key modulator of antiviral infections in human cells. Mechanistically, PA induces mitochondrial antiviral signaling protein (MAVS) palmitoylation, aggregation, and subsequent activation, thereby enhancing the innate immune response. The palmitoyl-transferase ZDHHC24 catalyzes MAVS palmitoylation, thereby boosting the TBK1-IRF3-interferon (IFN) pathway, particularly under conditions of PA stimulation or high-fat-diet-fed mouse models, leading to antiviral immune responses. Additionally, APT2 de-palmitoylates MAVS, thus inhibiting antiviral signaling, suggesting that its inhibitors, such as ML349, effectively reverse MAVS activation in response to antiviral infections. These findings underscore the critical role of PA in regulating antiviral innate immunity through MAVS palmitoylation and provide strategies for enhancing PA intake or targeting APT2 for combating viral infections.

Clinical analysis of Le Fort III distraction for obstructive sleep apnea in pediatric patients with syndromic craniosynostosis.

PURPOSE: This study aimed to analyze correlations among respiratory function, upper airway expansion, and the extent of midface advancement in syndromic craniosynostosis patients with obstructive sleep apnea. MATERIALS AND METHODS: A retrospective study was conducted in 21 children with syndromic craniosynostosis who underwent Le Fort III osteotomy and distractive osteogenesis at the Department of Oral and Maxillofacial Surgery of Peking University International Hospital from October 2017 to December 2022. Computed tomography (CT) data of patients before surgery (T0), 3 months after surgery (T1), and 1 year after surgery (T2) were reviewed. Sleep apnea was evaluated using polysomnography at the corresponding postoperative times. Skeletal changes were evaluated by cephalometric measurements; airway morphology was evaluated by two-dimensional cross square and three-dimensional volume; and respiratory function was measured using the apnea-hypopnea index (AHI), mean oxygen saturation (SpO2), minimum SpO2, and the 3% decline in the SpO2 index. A paired t-test was used to evaluate changes before and after surgery. A P value of <0.05 was considered to indicate statistical significance. Pearson correlation analysis was used to determine correlations among the skeletal structure, airway morphology, and respiratory function. RESULTS: Significant differences were noted between T0 and T1 in terms of cephalometry landmarks, airway volume, and cross-sectional area (P < 0.05) but not between T1 and T2 (P > 0.05). Similarly, significant differences were detected in AHI, average SpO2 level, minimum SpO2 level, and 3% oxygen hypoxia index between T0 and T1 but not between T1 and T2 (P > 0.05). The change in SN-PNS was significantly correlated with an improvement in AHI (P = 0.024) and 3% oxygen hypoxia index (P = 0.019), and the change in palatopharyngeal airway area(Ar B) was significantly correlated with an improvement in minimum SpO2 (P = 0.018). CONCLUSION: Le Fort III osteotomy and distraction are effective in enlarging the upper airway width and improving sleep apnea in syndromic craniosynostosis patients. Cephalometric changes in S-PNS and improvement in Ar B were correlated with long-term improvements in polysomnography outcomes.

Synthesis of ZIF-8/chitosan composites for Cu2+ removal from water.

In this work, a kind of novel Chitosan (Cs)-doped zeolite imidazole framework (ZIF-8@Cs) with a larger surface area and a smaller pore size was synthesised via a facial solvothermal approach and applied to remove Cu2+ from mine wastewater. Compared to nondoped ZIF-8, ZIF-8@Cs exhibited a stronger adsorption performance and removal efficiency. The reason was that ZIF-8@Cs doped by the Cs could suppress the aggregation and increase the monodispersity of ZIF-8. Using the high-performance ZIF-8@Cs, as a novel adsorbent, was successfully developed for the efficient removal of Cu2+ from mine wastewater. Various parameters, such as contact time, initial Cu2+ concentration, adsorbent dosage, and pH, were investigated. The results showed that a removal efficiency of 85% was obtained at 4 h contact time for a Cu2+ concentration of 30 mg/L at the optimum pH of 6.0. Equilibrium data were analysed using different isothermal models and kinetic models, analytic results indicated that the capture of Cu2+ by ZIF-8@Cs could favourably comply with the pseudo-first-order kinetic model and Langmuir isotherm model. The single-layer adsorption of Cu2+ on ZIF-8@Cs was dominated by diffusional mass transfer. Additionally, the results of the thermodynamic analysis indicated that the adsorption of Cu2+ by ZIF-8/Cs was a spontaneous, exothermic, and ordered process. Overall, the results reported herein indicated that ZIF-8/Cs with high adsorption efficiency are very attractive and imply a potential practical application for the removal of potentially toxic elements in wastewater.

Association between 35 blood and urine biomarkers and oral leukoplakia: a two-sample Mendelian randomization study.

Background: Several existing studies have shown a correlation between some of the blood and urine biomarkers and oral leukoplakia (OLK). However, the causality of this relationship remains uncertain. Thus, this study aimed to examine the causal association between 35 blood and urine biomarkers and OLK. Methods: Single nucleotide polymorphisms (SNPs) associated with 35 blood and urine biomarkers were selected as instrumental variables (IVs) using a two-sample Mendelian randomization(MR) study to assess the causal relationship between the biomarkers and the risk of oral leukoplakia. We used the inverse variance weighted (IVW) method as the main analysis. Furthermore, several sensitivity analyses were performed to assess heterogeneity, horizontal pleiotropy, and stability. Results: Based on the selection criteria of the Inverse Variance Weighted (IVW) method, the analysis found that 5 blood and urine biomarkers were significantly associated with the development of leukoplakia, of which the results of IVW showed that abnormalities of Apolipoprotein B (Apo B), Cholesterol, Low-density Lipoprotein (LDL), Triglycerides (TG) promoted the development of oral leukoplakia, and Non Albumin Protein (NAP) had a protective effect on the development of oral leukoplakia. We then performed a Bonferroni correction for these results, and after correction Apo B was still causally associated with the development of oral leukoplakia (IVW P<0.0007), whereas the other four biomarkers could only provide some evidence of predisposition. Conclusion: Our two-sample Mendelian randomization study supports the existence of a causal relationship between these five blood and urine biomarkers and the occurrence of oral leukoplakia, and provides evidence for a number of risk and protective factors for the development of oral leukoplakia; however, the definitive mechanisms for the occurrence and development of oral leukoplakia still remain to be elucidated, and further studies on these relevant mechanisms are still needed.

Apoptotic vesicle-mediated senolytics requires mechanical loading.

Rationale: Mechanical force plays crucial roles in extracellular vesicle biogenesis, release, composition and activity. However, it is unknown whether mechanical force regulates apoptotic vesicle (apoV) production. Methods: The effects of mechanical unloading on extracellular vesicles of bone marrow were evaluated through morphology, size distribution, yield, and protein mass spectrometry analysis using hindlimb unloading (HU) mouse model. Apoptosis resistance and aging related phenotype were assessed using HU mouse model in vivo and cell microgravity model in vitro. The therapeutic effects of apoVs on HU mouse model were assessed by using microcomputed tomography, histochemical and immunohistochemical, as well as histomorphometry analyses. SiRNA and chemicals were used for gain and loss-of-function assay. Results: In this study, we show that loss of mechanical force led to cellular apoptotic resistance and aging related phenotype, thus reducing the number of apoVs in the circulation due to down-regulated expression of Piezo1 and reduced calcium influx. And systemic infusion of apoVs was able to rescue Piezo1 expression and calcium influx, thereby, rescuing mechanical unloading-induced cellular apoptotic resistance, senescent cell accumulation. Conclusions: This study identified a previously unknown role of mechanical force in maintaining apoptotic homeostasis and eliminating senescent cells. Systemic infusion of mesenchymal stem cell-derived apoVs can effectively rescue apoptotic resistance and eliminate senescent cells in mechanical unloading mice.

Chlorogenic acid compounds from sweetpotato (Ipomoea batatas L.) leaves facilitate megakaryocyte differentiation and thrombocytopoiesis via PI3K/AKT pathway.

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by antiplatelet autoantibodies, thrombocytopenia, and bleeding, however, its treatment options are limited. In this study, a kind of active component, chlorogenic acid compounds (CGAs) from sweetpotato leaves was extracted out to explore its medicinal value and provide novel therapeutic strategies for the treatment of ITP. CGAs was isolated by ionic liquids-ultrasound (IL-UAE), which contains six isomers of chlorogenic acid with total purity of 95.69%. The thrombopoietic effect and mechanism of CGAs were investigated using in silico prediction and experimental validation. The changes of HEL cells morphology in volume and the increase in the total cell percentage of polyploid cells indicated that CGAs could promote megakaryocyte differentiation. Meanwhile, CGAs could promote platelet formation in a murine model of ITP, which was established by injection of antiplatelet antibody. Further quantitative proteomics analysis and Western blot verification revealed that CGAs could activate PI3K/AKT signaling pathway, which confirmed the mechanism prediction. It suggested that CGAs may provide a novel therapeutic strategy that relies on the PI3K/AKT pathway to facilitate megakaryocyte differentiation and platelet production.

Ultrasonic assessment of gastric solid contents in patients undergoing upper endoscope with sedation.

BACKGROUND: Perioperative reflux aspiration presents a grave concern during sedation or general anesthesia, particularly when solid gastric contents prompt acute upper respiratory obstruction, potentially resulting in fatal consequences for patients. Currently, there are limited means for promptly assessing solid gastric contents in clinical settings. Therefore, this study examined the efficacy of ultrasound assessment for solid gastric contents, offering a rapid and non-invasive approach for early detection and decision-making regarding interventions. METHODS: The study included 400 patients scheduled for upper endoscopy procedures, which encompassed both gastroscope and gastroscope combined colonoscopy examinations with sedation. Ultrasound scanning of the antrum was performed while patients were positioned semi-sitting or in the right lateral decubitus (RLD) posture. The evaluation of solid gastric contents relied on direct visual observation during endoscopy. Gastric volume measurement occurred subsequent to endoscopic suction of gastric contents. Receiver operating characteristic curves were utilized to assess the effectiveness of ultrasonography in discerning solid contents. RESULT: Seven patients undergoing gastroscope with sedation were found to have solid gastric contents. The sensitivity, specificity, positive predictive value, and negative predictive value of the ultrasound qualitative evaluation of solid contents were 85.7%, 99%, 60%, and 99.7%, respectively. CONCLUSION: Solid stomach contents can be evaluated qualitatively with reasonable accuracy using ultrasonography. Additionally, in patients undergoing upper endoscopy and assessed to have solid gastric contents with ultrasound, administration of mild sedation is recommended. TRIAL REGISTRATION: www.chictr.org.cn (ChiCTR2100048994); registered 19/07/2021.

Bioactive Peptides from Marine Organisms.

Marine organisms represent promising bioactive peptide resources with diverse biological activities such as antioxidant, antimicrobial, antihypertensive, anti-fatigue, and immunoregulatory activities. Despite many studies on marine bioactive peptides, there is a dearth of comprehensive review articles on the emerging trends that encompass the production techniques and the biological applications of marine bioactive peptides. In this review, we summarize the major research and findings related to marine bioactive peptides, encompassing aspects of their production, purification, biological activities, nanotechnology-based strategies, and their potential applications. Enzymatic hydrolysis currently stands out as the most commonly used method for producing marine bioactive peptides; the downstream purification process often includes a combination of multiple purification techniques. Due to their diverse biological properties, marine peptides have garnered considerable interest for industrial applications as active ingredients in the food, pharmaceutical, and cosmetics industries. Additionally, the incorporation of encapsulation strategies such as nano emulsion, nanoliposome, and microemulsions holds promise for significantly enhancing the bioavailability and bioactivity of marine peptides. Future research should also prioritize the systematic identification and validation of the potential health benefits of marine peptides by both in vitro and in vivo animal models, along with the conduct of human clinical trials.

Chemical structure and prebiotic activity of a Dictyophora indusiata polysaccharide fraction.

This study aimed to investigate the chemical structure and prebiotic activity of a Dictyophora indusiata polysaccharide fraction DIP0p. Our results indicated that DIP0p belongs to a heteropolysaccharide composed of glucose, galactose, mannose and xylose, accounting for 53.25 %, 24.18 %, 19.19 % and 3.37 %, respectively. Methylation and NMR results suggested that the main glycosidic bonds of DIP0p is →3)-Glcp-(1 â†’ with →4)-Glcp-(1→, →3,4)-Glcp-(1→, →3,4)-Galp-(1 â†’ and →6)-Manp-(1 â†’ branches. In addition, DIP0p increased the abundance of benificial bacteria during the in vitro fecal fermentation, including Phascolarctobacterium, Parabacteroides and Bifidobacterium. It is remarkable that DIP0p improved the level of acetic acid, propionic acid, and butyric acid of the fermentation system, which were 1.31, 1.52, and 2.64 folds higher than the Controls, respectively. In summary, this study comprehensively analyzed the structure and probiotic activity of DIP0p, which providing a theoretical basis for the development of the functional foods.

Initial dosage optimization of olanzapine in patients with bipolar disorder based on model-informed precision dosing: a study from the real world.

Objectives: Olanzapine is used for treating bipolar disorder (BPD); however, the optimal initial dosing regimen is unclear. The present study aimed to investigate the optimal olanzapine initial dosage in patients with BPD via model-informed precision dosing (MIPD) based on a real-world study. Methods: Thirty-nine patients with BPD from the real-world study were collected to construct the MIPD model. Results: Weight, combined used quetiapine influenced olanzapine clearances in patients with BPD, where the clearance rates were 0.152:1 in patients with or without quetiapine under the same weight. We simulated olanzapine doses once a day or twice a day, of which twice a day was optimal. Without quetiapine, for twice-a-day olanzapine doses, 0.80, 0.70, and 0.60 mg/kg/day were suitable for 40- to 56-kg BPD patients, 56- to 74-kg BPD patients, and 74- to 100-kg BPD patients, respectively. With quetiapine, for twice-a-day olanzapine doses, 0.05 mg/kg/day was suitable for 40- to 100-kg BPD patients. Conclusion: This study was the first to investigate the optimal olanzapine initial dosage in patients with BPD via MIPD based on a real-world study, providing clinical reference for the precision medication of olanzapine in BPD patients.

A case report of prolonged viral shedding of SARS-CoV-2 in a patient who receive ibrutinib for CLL therapy.

Patients on B cell immunosuppressive treatments have been shown to have persistent infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this report, a woman treated with ibrutinib for chronic lymphocytic leukemia experienced more than 40 days of coronavirus disease 2019 (COVID-19) infection. Unexpectedly, her peripheral blood experiments showed a normal SARS-CoV-2-specific antibody level and a relatively elevated percentage of CD19 + B cells, while an obvious decrease in the percentages of NK cells, CD4 + T cells and CD8 + T cells. Further SARS-CoV-2-specific T cell analysis in this patient indicated a significant decrease in the percentage of SARS-CoV-2-specific IFN-γ, TNF-α or IL-2 producing CD4 + T or CD8 + T cells. Most notably, ten days after the cease of ibrutinib, the PCR for SARS-CoV-2 turned negative and the reduced proportions of peripheral CD4 + T cells and CD8 + T cells recovered. Our research predicted that the depleted B-cell function therapies may play considerable role in the development of long COVID-19 and the abnormal T-cell subset distribution might be the underlying mechanism.