Investigating the L-Glu-NMDA receptor-H2S-NMDA receptor pathway that regulates gastric function in rats' nucleus ambiguus.

Background: In previous investigations, we explored the regulation of gastric function by hydrogen sulfide (H2S) and L-glutamate (L-Glu) injections in the nucleus ambiguus (NA). We also determined that both H2S and L-Glu have roles to play in the physiological activities of the body, and that NA is an important nucleus for receiving visceral sensations. The purpose of this study was to explore the potential pathway link between L-Glu and H2S, resulting in the regulation of gastric function. Methods: Physiological saline (PS), L-glutamate (L-Glu, 2 nmol), NaHS (2 nmol), D-2-amino-5-phopho-novalerate (D-AP5, 2 nmol) + L-Glu (2 nmol), aminooxyacetic acid (AOAA, 2 nmol) + L-Glu (2 nmol), D-AP5 (2 nmol) + NaHS (2 nmol) were injected into the NA. A balloon was inserted into the stomach to observe gastric pressure and for recording the changes of gastric smooth muscle contraction curve. The gastric fluid was collected by esophageal perfusion and for recording the change of gastric pH value. Results: Injecting L-Glu in NA was found to significantly inhibit gastric motility and promote gastric acid secretion in rats (p < 0.01). On the other hand, injecting the PS, pre-injection N-methyl-D-aspartate (NMDA) receptor blocker D-AP5, cystathionine beta-synthase (CBS) inhibitor AOAA and re-injection L-Glu did not result in significant changes (p > 0.05). The same injection NaHS significantly inhibit gastric motility and promote gastric acid secretion in rats (p < 0.01), but is eliminated by injection D-AP5 (p > 0.05). Conclusion: The results indicate that both exogenous L-Glu and H2S injected in NA regulate gastric motility and gastric acid secretion through NMDA receptors. This suggests that NA has an L-Glu-NMDA receptor-CBS-H2S pathway that regulates gastric function.

Development and validation of pharmacokinetics assays for a novel HER2-targeting antibody-drug conjugate (SHR-A1201): Application to its dose-escalation pharmacokinetic study.

Approximately 25% of breast cancer patients with HER2 overexpression tend to have a high risk of disease progression and death. Various HER2-targeting therapies have been approved for treatment. Recently, a novel antibody-drug conjugate, SHR-A1201, is being researched and developed. For the pharmacokinetic study of SHR-A1201, suitable bioanalytical methods are needed for quantifying unconjugated cytotoxin, cytotoxin-conjugated antibodies and total antibodies. In this research, bioanalytical methods involving a highly sensitive LC-MS/MS assay for unconjugated cytotoxic payload DM1 in human plasma, ELISA strategies for DM1-conjugated trastuzumab and total trastuzumab in human serum were developed, validated and successfully applied to a phase I dose-escalation pharmacokinetic study of SHR-A1201. The pharmacokinetic properties and exposure-to-dose proportionality was evaluated for SHR-A1201. According to the bioanalytical method validation guidance, the bioanalytical methods were fully validated and the validation results met the acceptance criteria. The nonspecific binding of DM1 and dimer was avoided for the LC-MS/MS assay. In the dose-escalation pharmacokinetic study of SHR-A1201, a potential dose-proportional pharmacokinetics was observed over the dose from 1.2 mg/kg to 4.8 mg/kg. The validated bioanalytical strategies are robust and reproducible and these bioanalytical methods will contribute to better understanding of the pharmacokinetic properties of SHR-A1201.

Corrigendum: Work engagement and associated factors among healthcare professionals in the post-pandemic era: a cross-sectional study.

[This corrects the article DOI: 10.3389/fpubh.2023.1173117.].

Effect of exogenous hydrogen sulfide in the nucleus tractus solitarius on gastric motility in rats.

BACKGROUND: Hydrogen sulfide (H2S) is a recently discovered gaseous neurotransmitter in the nervous and gastrointestinal systems. It exerts its effects through multiple signaling pathways, impacting various physiological activities. The nucleus tractus solitarius (NTS), a vital nucleus involved in visceral sensation, was investigated in this study to understand the role of H2S in regulating gastric function in rats. AIM: To examine whether H2S affects the nuclear factor kappa-B (NF-κB) and transient receptor potential vanilloid 1 pathways and the neurokinin 1 (NK1) receptor in the NTS. METHODS: Immunohistochemical and fluorescent double-labeling techniques were employed to identify cystathionine beta-synthase (CBS) and c-Fos co-expressed positive neurons in the NTS during rat stress. Gastric motility curves were recorded by inserting a pressure-sensing balloon into the pylorus through the stomach fundus. Changes in gastric motility were observed before and after injecting different doses of NaHS (4 nmol and 8 nmol), physiological saline, Capsazepine (4 nmol) + NaHS (4 nmol), pyrrolidine dithiocarbamate (PDTC, 4 nmol) + NaHS (4 nmol), and L703606 (4 nmol) + NaHS (4 nmol). RESULTS: We identified a significant increase in the co-expression of c-Fos and CBS positive neurons in the NTS after 1 h and 3 h of restraint water-immersion stress compared to the expressions observed in the control group. Intra-NTS injection of NaHS at different doses significantly inhibited gastric motility in rats (P < 0.01). However, injection of saline, first injection NF-κB inhibitor PDTC or transient receptor potential vanilloid 1 (TRPV1) antagonist Capsazepine or NK1 receptor blockers L703606 and then injection NaHS did not produce significant changes (P > 0.05). CONCLUSION: NTS contains neurons co-expressing CBS and c-Fos, and the injection of NaHS into the NTS can suppress gastric motility in rats. This effect may be mediated by activating TRPV1 and NK1 receptors via the NF-κB channel.

Work engagement and associated factors among healthcare professionals in the post-pandemic era: a cross-sectional study.

Background: With the shift of strategy in fighting COVID-19, the post-pandemic era is approaching. However, the "hard times" for healthcare systems worldwide are not yet ending. Healthcare professionals suffer negative impacts caused by the epidemic, which may seriously threaten their work motivation, concentration, and patient safety. Objective: Investigating the status and factors associated with Chinese healthcare professionals' work engagement in the post-pandemic era. Methods: A cross-sectional study was conducted to investigate healthcare professionals from 10 hospitals in Hunan Province. Data were collected using demographic characteristics, Generalized Anxiety Disorder-2, Patient Heath Qstionaire-2, Utrecht Work Engagement Scale, Work-Related Basic Need Satisfaction Scale, National Aeronautics and Space Administration-Task Load Index, and self-compassion scale. Descriptive and multiple linear regression analyses explored the factors associated with work engagement. Results: A total of 1,037 eligible healthcare professionals participated in this study, including 46.4% of physicians, 47.8% of nurses, and 5.8% of others. The total mean score of work engagement was 3.36 ± 1.14. The main predictor variables of work engagement were gender (p = 0.007), years of work experience (p < 0.001), whether currently suffering challenges in the care of patients with COVID-19 (p = 0.003), depression (p < 0.001), work-related basic need satisfaction (p < 0.001), and mindfulness (p < 0.001). Conclusion: Healthcare professionals have a medium level of work engagement. Managers need to pay attention to the physical and psychological health of healthcare professionals, provide adequate support, help them overcome challenges, and acknowledge their contribution and value to improve their work engagement, enhance the quality of care and ensure patient safety.

New findings on choroidal features in healthy people by ultra-widefield swept-source optical coherence tomography angiography.

To evaluate the distribution of choroidal thickness (CT) and its trend with age in healthy people using 120° ultra-wide field swept-source optical coherence tomography angiography (UWF SS-OCTA). In this cross-sectional observational study, healthy volunteers underwent single imaging of the fundus with UWF SS-OCTA at a field of view (FOV) of 120° (24 mm × 20 mm) centered on the macula. The characteristics of CT distribution in different regions and its changes with age were analyzed. A total of 128 volunteers with a mean age of 34.9 ± 20.1 years and 210 eyes were enrolled in the study. The thickest mean choroid thickness (MCT) was located at the macular region and supratemporal region, followed by the nasal side of the optic disc, and thinnest below the optic disc. The maximum MCT was: 213.40 ± 36.65 µm for the group aged 20-29, and the minimum MCT was: 162.11 ± 31.96 µm for the group aged ≥ 60. After the age of 50, MCT was significantly and negatively correlated decreased with age (r = - 0.358, p = 0.002), and the MCT in the macular region decreased more remarkably compared to other regions. The 120° UWF SS-OCTA can observe the distribution of choroidal thickness in the range of 24 mm × 20 mm and its variation with age. It was revealed that MCT decreased more rapidly in the macular region relative to other regions after 50 years old.

Different scan areas affect the detection rates of diabetic retinopathy lesions by high-speed ultra-widefield swept-source optical coherence tomography angiography.

Introduction: The study aimed to determine the effect of the scanning area used for high-speed ultra-widefield swept-source optical coherence tomography angiography (SS-OCTA) on the detection rate of diabetic retinopathy (DR) lesions. Methods: This prospective, observational study involved diabetic patients between October 2021 and April 2022. The participants underwent a comprehensive ophthalmic examination and high-speed ultra-widefield SS-OCTA using a 24 mm × 20 mm scanning protocol. A central area denoted as "12 mm × 12 mm-central" was extracted from the 24 mm × 20 mm image, and the remaining area was denoted as "12 mm~24mm-annulus." The rates of detection of DR lesions using the two scanning areas were recorded and compared. Results: In total, 172 eyes (41 eyes with diabetes mellitus without DR, 40 eyes with mild to moderate non-proliferative diabetic retinopathy (NPDR), 51 eyes with severe NPDR, and 40 eyes with proliferative diabetic retinopathy (PDR) from 101 participants were included. The detection rates of microaneurysms (MAs), intraretinal microvascular abnormalities (IRMAs), and neovascularization (NV) for the 12 mm × 12 mm central and 24 mm × 20 mm images were comparable (p > 0.05). The detection rate of NPAs for the 24 mm × 20 mm image was 64.5%, which was significantly higher than that for the 12 mm × 12 mm central image (52.3%, p < 0.05). The average ischemic index (ISI) was 15.26% for the 12 mm~24mm-annulus, which was significantly higher than that for the 12 mm × 12 mm central image (5.62%). Six eyes had NV and 10 eyes had IRMAs that only existed in the 12 mm~24mm-annulus area. Conclusions: The newly developed high-speed ultra-widefield SS-OCTA can capture a 24 mm × 20 mm retinal vascular image during a single scan, which improves the accuracy of detecting the degree of retinal ischemia and detection rate of NV and IRMAs.

A super water-resistant MXene sponge flexible sensor for bifunctional sensing of physical and chemical stimuli.

Flexible wearable sensors with multifunctional features have attracted great interest in various applications such as disease diagnosis, environmental detection and healthcare monitoring. However, it is still a challenge to achieve a multifunctional sensor with super water resistance without compromising the overall performance of the sensing material. Here, we developed a 3D bifunctional flexible sensor based on an MXene melamine sponge (MS) through a simple and effective ultrasonic mixing process and a further vacuum annealing process. The sensor is able to show excellent response to different stimuli, including pressure and humidity. The thermal annealing treatment allows MXene to adhere more firmly to the internal skeleton of the sponge, which does not easily fall off and improves the water resistance, thus achieving wearability and high sensitivity over a wide area. The T-MXene@MS sensor has a sensitivity of 9.97 kPa-1 in the 5-15 kPa range, a fast response time (180 ms), and good stability at 4000 cycles, enabling accurate monitoring of human movement. The sensor has a rich porous structure while maintaining its inherent flexibility, which allows for long term testing of human respiration as well as the ability to respond quickly to dynamic changes in humidity, demonstrating excellent long-term stability for 40 days of humidity detection.

Psychological stress and associated factors in caring for patients with delirium among intensive care unit nurses: A cross-sectional study.

BACKGROUND: Caring for patients with delirium is challenging and overwhelming for intensive care unit (ICU) nurses. Investigating the psychological impact of delirium care on ICU nurses is crucial to maintaining their psychological health and improving the quality of care. OBJECTIVE: The objective of this study was to investigate the psychological stress of ICU nurses in caring for patients with delirium and potential factors. METHODS: A total of 355 nurses from three tertiary care hospitals in Hunan Province, China, participated in this cross-sectional survey. Data were collected using the demographic sheet, Impact of Event Scale-Revised, Connor-Davidson Resilience Scale, and Occupational Coping Self-Efficacy Scale for Nurses. Descriptive and multiple linear regression analyses were used to examine the factors associated with psychological stress. RESULTS: ICU nurses suffered moderate psychological stress related to delirium care. The recent time to care for patients with delirium (P < 0.001), familiarity with delirium-related knowledge (P = 0.002), satisfaction with delirium-related support (P = 0.046), psychological resilience (P < 0.001), and occupational coping self-efficacy (P < 0.001) were significant contributors to psychological stress. CONCLUSION: Nurse managers and researchers need to focus on the psychological well-being of ICU nurses in caring for patients with delirium, especially those who are currently caring for patients with delirium, and provide tailored support, increase their knowledge of delirium, and also boost psychological resilience and coping skills.

Ultra-widefield color fundus photography combined with high-speed ultra-widefield swept-source optical coherence tomography angiography for non-invasive detection of lesions in diabetic retinopathy.

Purpose: To compare the detection rate of diabetic retinopathy (DR) lesions and the agreement of DR severity grading using the ultra-widefield color fundus photography (UWF CFP) combined with high-speed ultra-widefield swept-source optical coherence tomography angiography (UWF SS-OCTA) or fluorescein angiography (FFA). Methods: This prospective, observational study recruited diabetic patients who had already taken the FFA examination from November 2021 to June 2022. These patients had either no DR or any stage of DR. All participants were imaged with a 200° UWF CFP and UWF SS-OCTA using a 24 × 20 mm scan model. Images were independently evaluated for the presence or absence of DR lesions including microaneurysms (MAs), intraretinal hemorrhage (IRH), non-perfusion areas (NPAs), intraretinal microvascular abnormalities (IRMAs), venous beading (VB), neovascularization elsewhere (NVE), neovascularization of the optic disc (NVD), and vitreous or preretinal hemorrhage (VH/PRH). Agreement of DR severity grading based on UWF CFP plus UWF SS-OCTA and UWF CFP plus FFA was compared. All statistical analyses were performed using SPSS V.26.0. Results: One hundred and fifty-three eyes of 86 participants were enrolled in the study. The combination of UWF CFP with UWF SS-OCTA showed a similar detection rate compared with UWF CFP plus FFA for all the characteristic DR lesions (p>0.05), except NPAs (p = 0.039). Good agreement was shown for the identification of VB (κ = 0.635), and very good agreement for rest of the DR lesions between the two combination methods (κ-value ranged from 0.858 to 0.974). When comparing the grading of DR severity, very good agreement was achieved between UWF CFP plus UWF SS-OCTA and UWF CFP plusr FFA (κ = 0.869). Conclusion: UWF CFP plus UWF SS-OCTA had a very good agreement in detecting DR lesions and determining the severity of DR compared with UWF CFP plus FFA. This modality has the potential to be used as a fast, reliable, and non-invasive method for DR screening and monitoring in the future.

A Novel Single-Nucleotide Polymorphism in WNT4 Promoter Affects Its Transcription and Response to FSH in Chicken Follicles.

The signaling pathway of the wingless-type mouse mammary tumor virus integration site (Wnt) plays an important role in ovarian and follicular development. In our previous study, WNT4 was shown to be involved in the selection and development of chicken follicles by upregulating the expression of follicle-stimulating hormone receptors (FSHR), stimulating the proliferation of follicular granulosa cells, and increasing the secretion of steroidal hormones. FSH also stimulates the expression of WNT4. To further explore the molecular mechanism by which FSH upregulates WNT4 and characterize the cis-elements regulating WNT4 transcription, in this study, we determined the critical regulatory regions affecting chicken WNT4 transcription. We then identified a single-nucleotide polymorphism (SNP) in this region, and finally analyzed the associations of the SNP with chicken production traits. The results showed that the 5' regulatory region from −3354 to −2689 of WNT4 had the strongest activity and greatest response to FSH stimulation, and we identified one SNP site in this segment, −3015 (G > C), as affecting the binding of NFAT5 (nuclear factor of activated T cells 5) and respones to FSH stimulation. When G was replaced with C at this site, it eliminated the NFAT5 binding. The mRNA level of WNT4 in small yellow follicles of chickens with genotype GG was significantly higher than that of the other two genotypes. Moreover, this locus was found to be significantly associated with comb length in hens. Individuals with the genotype CC had longer combs. Collectively, these data suggested that SNP−3015 (G > C) is involved in the regulation of WNT4 gene expression by responding FSH and affecting the binding of NFAT5 and that it is associated with chicken comb length. The current results provide a reference for further revealing the response mechanism between WNT and FSH.

Pharmacokinetic and pharmacodynamic similarity evaluation between an insulin glargine biosimilar product and Lantus® in healthy subjects: Pharmacokinetic parameters of both parent insulin glargine and M1 were used as endpoints.

Insulin glargine is a long-acting insulin analog, which plays an important role in the treatment of diabetes mellitus. Biosimilar products of insulin glargine can provide patients with additional safe, high-quality, and potentially cost-effective options for treating diabetes. This article presents a randomized, double-blind, single-dose, two-treatment, four-period, replicate crossover, euglycemic clamp study which was designed to evaluate the PK and PD similarity between the recombinant insulin glargine developed by Wanbang (test) and Lantus® (reference) in healthy volunteers. Subjects received subcutaneous administration of the insulin glargine formulation (0.4 U/kg) on two occasions for the test and reference drug, respectively, and a 20% dextrose solution was infused at variable rate to clamp the blood glucose concentrations at 0.3 mmol/L below the subjects' fasting glucose for 24 h. Taking advantage of the improved sensitivity of the bioanalytical method applied and the solution of the matrix stability problem, the parent insulin glargine was determined in the vast majority of plasma samples using a fully validated UHPLC-MS/MS method. The PK characteristics of the parent insulin glargine were revealed for the first time: after subcutaneous injection, concentrations of the parent insulin glargine increased to a relative high level within 3 h, and then, a relatively flat concentration-time profile lasting for at least 12 h post-dose was observed. For the first time, the pharmacokinetic parameters of the parent insulin glargine were used as endpoints for similarity evaluation, which complied with the regulatory guidance better and made the similarity conclusion more powerful. The ratios of geometric means of all PK and PD endpoints were close to 100.00%. For the PK endpoints (AUC0-24h, Cmax, AUC0-12h, and AUC12-24h of the parent insulin glargine and its metabolite M1), the 90% confidence intervals of geometric mean ratios of test to reference were entirely contained within 80.00%-125.00%. For the PD endpoints [AUCGIR(0-24h), GIRmax, AUCGIR(0-12h), and AUCGIR(12-24h)], the 95% confidence intervals of geometric mean ratios of test to reference were entirely contained within 80.00%-125.00%. Based on the above mentioned results, it can be concluded that the PK and PD characteristics of the biosimilar drug developed by Wanbang are similar to those of Lantus.

Identification and characterization of a thermostable GH11 xylanase from Paenibacillus campinasensis NTU-11 and the distinct roles of its carbohydrate-binding domain and linker sequence.

An extracellular thermostable xylanase (XynNTU) from Paenibacillus campinasensis NTU-11, consisted of a glycoside hydrolase (GH) family 11 catalytic domain, a Gly/Pro-rich linker sequence (LS) and a family 6 carbohydrate-binding module (CBM6), was identified and expressed in E. coli BL21. The purified XynNTU had a specific activity of 2750 U/mg and an optimal activity at 60 °C and pH 7.0, and retained a residual activity of 58.4% after incubation (60 °C, 48 h). Two truncated mutants, CBM6-truncated form XynNTU-CDLS, CBM6 and linker-truncated form XynNTU-CD, possessed similar values of optimum pH and temperature as the native XynNTU. XynNTU-CD displayed a lower thermostability than XynNTU, whereas for XynNTU-CDLS, more than 90% of residual activity was remained (60 °C, 48 h), indicating that this enzyme presented a higher thermostability than that of the majority of reported GH11 xylanases. Furthermore, XynNTU and two mutants maintained more than 70% of residual activity at pH values of 5-9. Kinetic measurements suggested that CBM6 had a crucial function in the ability of the enzyme to bind and hydrolyze xylan substrates, while LS had a relatively mild influence. Collectively, a noticeable thermostability and a high specific activity of XynNTU and its truncated form XynNTU-CDLS highlights their potentials for diverse industrial applications.

Resolvin D2 suppresses NLRP3 inflammasome by promoting autophagy in macrophages.

Inflammasome, a multiprotein complex that regulates interleukin (IL)-1ß secretion and pyroptosis, participates in numerous inflammatory diseases, including sepsis, atherosclerosis and type-2 diabetes. Investigating the inflammasome regulation is therefore crucial to understand the inflammasome activation and develop treatment for the related diseases. In addition, it remains unknown how the inflammasome is naturally suppressed during the inflammatory process. The present study aimed to investigate the role of resolvin D2 (RvD2), an innate suppressor of inflammation produced from essential ω3-polyunsaturated fatty acids, in the activation of the inflammasome via in vitro and in vivo experiments. The effects of RvD2 on the cytokine production of inflammasome-related peritonitis were determined, and the NLRP3 inflammasome activation was investigated in the presence of RvD2. Moreover, the potential mechanisms underlying RvD2 in NLRP3 inflammasome regulation through autophagy and proteasome were investigated. The results of the present study demonstrated that RvD2 suppressed inflammasome-mediated peritonitis in vivo and regulated the NLR family pyrin domain containing 3 (NLRP3) inflammasome, but not in absent in melanoma 2 (AIM2), NLR family CARD domain containing 4 (NLRC4) inflammasomes. Mechanistically, RvD2 was found to promote the degradation of NLRP3 through autophagy, and the inhibition of autophagy could reverse the RvD2-mediated suppression of NLRP3 inflammasome in vitro and partially reverse the inflammasome-mediated peritonitis in vivo. In summary, the present study reported the negative regulation of NLRP3 inflammasome activation by RvD2. The findings from this study may extend the knowledge of the innate regulation of inflammasome and highlight a possible target for inflammasome-related diseases.

Low Molar Mass Dextran: One-Step Synthesis With Dextransucrase by Site-Directed Mutagenesis and its Potential of Iron-Loading.

Iron dextran is a common anti-anemia drug, and it requires low molar mass dextran as substrate. In this work, we selected 11 amino acid residues in domain A/B of DSR-MΔ2 within a 5-angstrom distance from sucrose for site-directed mutagenesis by molecular docking. Mutation of Q634 did not affect the enzyme catalytic activity, but showed an obvious impact on the ratio of low molecular weight dextran (L-dextran, 3,000-5,000 Da) and relatively higher molecular weight dextran (H-dextran, around 10,000 Da). L-dextran was the main product synthesized by DSR-MΔ2 Q634A, and its average molecular weight was 3,951 Da with a polydispersity index <1.3. The structural characterization of this homopolysaccharide revealed that it was a dextran, with 86.0% α(1→6) and 14.0% α(1→4) glycosidic linkages. Moreover, L-dextran was oxidized with NaOH and chelated with ferric trichloride, and an OL-dextran-iron complex was synthesized with a high iron-loading potential of 33.5% (w/w). Altogether, mutation of amino acids near the sucrose binding site of dextransucrase can affect the chain elongation process, making it possible to modulate dextran size.

The Distribution and Localization of Collagen Triple Helix Repeat Containing-1 in Naturally and Experimentally Avian Leukosis Virus Subgroup J-Infected Chickens.

Collagen triple helix repeat containing-1 (CTHRC1) has recently been identified as avian leukosis virus subgroup J (ALV-J) replication-dependent factor that remarkably facilitates ALV-J replication via interaction with the envelope glycoprotein (SU) of ALV-J. However, the dynamic distribution and localization of CTHRC1 in various tissues upon ALV-J infection are still unknown. In this study, data revealed that the levels of CTHRC1 were significantly increased in various tissues and that the protein was mainly located in the cytoplasm and nucleus of parenchymal cells in tissues of chickens that were infected by ALV-J naturally and experimentally. Interestingly, CTHRC1 was also observed in leukocytes other than erythrocytes in congested veins of ALV-J-infected tissues. Consequently, the positive cells in these veins were confirmed as lymphocytes by laser confocal microscopy. Taken together, these results conclude that the CTHRC1 is an inducible protein and exhibited ubiquitous expression in ALV-J-infected chickens, which may provide basic information for in-depth study of ALV-J infection and replication mechanisms.

Tolerability, Safety, Pharmacokinetics and Drug Interaction of Cefotaxime Sodium-Tazobactam Sodium Injection (6:1) Following Single and Multiple Intravenous Doses in Chinese Healthy Subjects.

PURPOSE: To evaluate the tolerability, safety, pharmacokinetics and drug interaction of cefotaxime sodium-tazobactam sodium injection (6:1) in Chinese healthy subjects. The results of the safety and pharmacokinetic studies supported further clinical trials. METHOD: A randomized, single-blind, ascending dose, placebo-controlled, single-center study was conducted. Sixty healthy subjects (38 males, 22 females) participated in this study. For the single-dose part, 0.47, 1.17, 2.34, 3.51, and 4.68 g of cefotaxime sodium-tazobactam sodium injection (6:1) was administered. For the multiple-dose part, the subjects were administered 2.34 and 3.51 g cefotaxime sodium-tazobactam sodium injection (6:1) three times a day for 7 consecutive days. For the drug interaction part, the subjects received 2.0 g cefotaxime sodium and 0.34 g tazobactam sodium alone and in combination. RESULTS: Most adverse events and adverse drug reactions were mild. Moderate rash was considered a serious adverse event because of prolongation of hospitalization. The main pharmacokinetic parameters of cefotaxime and tazobactam had no significance difference between the 1.17, 2.34, and 3.51 g dose cohorts and between genders. There was no difference in trough concentrations on days 6, 7, and 8. The R C max and R AUC were (0.921 ± 0.070) and (0.877 ± 0.057) for cefotaxime, and (0.913 ± 0.046) and (0.853 ± 0.060) for tazobactam, respectively. Following the administration of cefotaxime and tazobactam alone and in combination, the 90% confidence intervals of the geometric mean ratios for C max and AUC were within the predetermined range of 80-125%. In the single-dose part, the renal cumulative excretion ratios were (51.7 ± 6.2)% for cefotaxime, and (84.3 ± 8.1)% for tazobactam. There was no significant difference in the maximum excretion rates and cumulative excretion ratios for cefotaxime and tazobactam, alone or in combination. CONCLUSIONS: Cefotaxime sodium-tazobactam sodium injection (6:1) was well-tolerated at doses of 0.47 to 4.68 g. The pharmacokinetics of cefotaxime and tazobactam were reported as linear over a dose range of 1.17-3.51 g. Cefotaxime was partially excreted via urine, whereas tazobactam was mainly excreted via urine. There was no significant accumulation after administration over 7 consecutive days. The pharmacokinetics and excretion of cefotaxime and tazobactam were not affected by the co-administration of cefotaxime-tazobactam.

Transcriptomic and proteomic analyses of ovarian follicles reveal the role of VLDLR in chicken follicle selection.

BACKGROUND: Follicle selection in chickens refers to the process of selecting one follicle from a group of small yellow follicles (SY, 6-8 mm in diameter) for development into 12-15 mm hierarchical follicles (usually F6 follicles), which is an important process affecting laying performance in the poultry industry. Although transcriptomic analysis of chicken ovarian follicles has been reported, integrated analysis of chicken follicles for selection by using both transcriptomic and proteomic approaches is still rarely performed. In this study, we compared the proteomes and transcriptomes of SY and F6 follicles in laying hens and identified several genes involved in chicken follicle selection. RESULTS: Transcriptomic analysis revealed 855 differentially expressed genes (DEGs) between SY follicles and F6 follicles in laying hens, among which 202 were upregulated and 653 were downregulated. Proteomic analysis revealed 259 differentially expressed proteins (DEPs), including 175 upregulated and 84 downregulated proteins. Among the identified DEGs and DEPs, changes in the expression of seven genes, including VLDLR1, WIF1, NGFR, AMH, BMP15, GDF6 and MMP13, and nine proteins, including VLDLR, VTG1, VTG3, PSCA, APOB, APOV1, F10, ZP2 and ZP3L2, were validated. Further analysis indicated that the mRNA level of chicken VLDLR was higher in F6 follicles than in SY follicles and was also higher in granulosa cells (GCs) than in thecal cells (TCs), and it was stimulated by FSH in GCs. CONCLUSIONS: By comparing the proteomes and transcriptomes of SY and F6 follicles in laying hens, we identified several differentially expressed proteins/genes that might play certain roles in chicken follicle selection. These data may contribute to the identification of functional genes and proteins involved in chicken follicle selection.

Stem Cell-Based Delivery of Gold/Chlorin e6 Nanocomplexes for Combined Photothermal and Photodynamic Therapy.

Combining photothermal and photodynamic modalities has shown encouraging therapeutic efficacy against various malignant cancers. Developing a delivery method for targeting and penetrating tumors is still a major focus for advancing this therapeutic approach. Herein, we report a novel strategy involving the utilization of stem cells as a live carrier to codeliver photothermal and photodynamic agents for cancer therapy. To this end, a novel gold nanorod (AuNR)-PEG-PEI (APP)/chlorin e6 (Ce6)-loaded adipose-derived stem cell (ADSC) system is proposed in which AuNRs and Ce6 act as the photothermal and photodynamic agents, respectively. To integrate with stem cells, the APP/Ce6 nanocomplexes exhibit advantages of low drug leakage, low cytotoxicity, efficient cellular uptake, and redox-responsive release. After loading of APP/Ce6 nanocomplexes, the ADSCs still maintained good tumor tropism and were capable of penetrating into the tumor spheroids. The photothermal effect induced by exposure to near-infrared light irradiation at 808 nm promoted the release of Ce6 from the stem cells into the surroundings and hence increased its availability to treat cancer cells. APP/Ce6-loaded ADSCs exerted effective dose-dependent in vitro anticancer activities via anticipated photothermal and photodynamic effects. In a murine CT26 colon cancer model, APP/Ce6 delivered by ADSCs resulted in superior tumor suppression compared to other delivery strategies. It was also noted that in vivo applications of APP/Ce6-loaded ADSCs did not induce noticeable detrimental effects on normal tissues/organs.

Experimental Study of the Influences of Temperature on the Properties of Particles in a Gasifier during Coal-Water Slurry Gasification.

Studies were made on the influence of temperature and oxygen to carbon ratio (the O/C ratio) on the properties of particles during water coal slurry gasification by taking a new-type coal-water slurry gasifier as the thermal experiment platform, coal-water slurry as a gasification material, and oxygen as the oxidant. The results show that the higher the gasification temperature, the more spherical particles are generated, the higher the content of Na, Fe, and S on the particle surface, and the greater the mass percentage of fine particles. With increase in the O/C ratio, the production of fine particles also increases, while the carbon content of the particles decreases. When the O/C ratio is 1.1, fine particles mainly exist in the form of aggregates; the O/C ratio has little influence on the contents of the particle surface, such as Na, Al, Si, Fe, and S. The effect of the O/C ratio on particle size distribution is most obvious when the ratio is 1: the fine particles are the most prevalent and the coarse particles are the fewest. When the ratio is 1.1, the amount of coarse particles is the largest and the amount of fine particle aggregates is also greater. When the ratio is 0.9, the particle size distribution is intermediate to the two cases.