Intravenous calcitriol administration improves the liver redox status and attenuates ferroptosis in mice with high-fat diet-induced obesity complicated with sepsis.

Obesity aggravates ferroptosis, and vitamin D (VD) may inhibit ferroptosis. We hypothesized that weight reduction and/or calcitriol administration have benefits against the sepsis-induced liver redox imbalance and ferroptosis in obese mice. Mice were fed a high-fat diet for 11 weeks, then half of the mice continued to consume the diet, while the other half were transferred to a low-energy diet for 5 weeks. After feeding the respective diets for 16 weeks, sepsis was induced by cecal ligation and puncture (CLP). Septic mice were divided into four experimental groups: OS group, obese mice injected with saline; OD group, obese mice with calcitriol; WS group, weight-reduction mice with saline; and WD group, weight-reduction mice with calcitriol. Mice in the respective groups were euthanized at 12 or 24 h after CLP. Results showed that the OS group had the highest inflammatory mediators and lipid peroxide levels in the liver. Calcitriol treatment reduced iron content, enhanced the reduced glutathione/oxidized glutathione ratio, upregulated nuclear factor erythroid 2-related factor 2, ferroptosis-suppressing protein 1, and solute carrier family 7 member 11 expression levels. Also, mitochondrion-associated nicotinamide adenine dinucleotide phosphate oxidase 1, peroxisome proliferator-activated receptor-γ coactivator 1, hypoxia-inducible factor-1α, and heme oxidase-1 expression levels increased in the late phase of sepsis. These results were not noted in the WS group. These findings suggest that calcitriol treatment elicits a more-balanced glutathione redox status, alleviates liver ferroptosis, and enhances mitochondrial biogenesis-associated gene expressions. Weight reduction alone had minimal influences on liver ferroptosis and mitochondrial biogenesis in obese mice with sepsis.

A Membrane-Free Rechargeable Seawater Battery Unlocked by Lattice Engineering.

Seawater batteries that directly utilize natural seawater as electrolytes are ideal sustainable aqueous devices with high safety, exceedingly low cost, and environmental friendliness. However, the present seawater batteries are either primary batteries or rechargeable half-seawater/half-nonaqueous batteries because of the lack of suitable anode working in seawater. Here, a unique lattice engineering to unlock the electrochemically inert anatase TiO2 anode to be highly active for the reversible uptake of multiple cations (Na+, Mg2+, and Ca2+) in aqueous electrolytes is demonstrated. Density functional theory calculations further reveal the origin of the unprecedented charge storage behaviors, which can be attributed to the significant reduction of the cations diffusion barrier within the lattice, i.e., from 1.5 to 0.4 eV. As a result, the capacities of anatase TiO2 with 2.4% lattice expansion are ≈100 times higher than the routine one in natural seawater, and ≈200 times higher in aqueous Na+ electrolyte. The finding will significantly advance aqueous seawater energy storage devices closer to practical applications.

Placement of Nasogastric Tubes in Pancreaticoduodenectomy Patients: Switching from Immediate Intraoperative Removal to Avoiding Unnecessary Perioperative Use.

BACKGROUND: The placement of nasogastric tubes (NGTs) in abdominal surgery has been adopted for decades to attenuate ileus and prevent aspiration pneumonia. In the recent era, the guidelines recommend not using NGT routinely, and even in pancreaticoduodenectomy (PD), immediate removal of NGT in operating rooms (ORs) was suggested. However, the clinical outcome and safety of abandoning NGT during the pre-PD and intra-PD periods remain unknown. METHODS: We conducted a single-center retrospective review on adult PD patients aged between 20 and 75 years from 2013 to 2022. The study population was grouped into the NGT group (NGT was placed before PD and immediately removed in the ORs) and the non-NGT group (NGT was not placed preoperatively). Safety was evaluated by the number of adverse events. The primary aim of this study is to evaluate the need of NGT insertion in ORs among PD patients. RESULTS: The case numbers in the NGT and non-NGT groups were 391 and 578, respectively. No case in the non-NGT group needed the intraoperative insertion of NGT. The rate of pulmonary complications was 2.3% in the NGT group compared to 1.6% in the non-NGT group (P = 0.400). Furthermore, there were no significant differences in terms of rates of major complications (12.8% vs. 9.3%, P = 0.089) or mortality (1.0% vs. 1.0%, P =0.980) between the two groups. The rates of the postoperative insertion of NGT in the NGT and non-NGT groups were 2.6% and 2.8% (P = 0.840), respectively. CONCLUSION: For selected PD patients, the placement of NGT during pre-PD and intra-PD periods may be safely omitted. This primary study is considered the first foundation stone in the extension of the element of no NGT in PD.

A H2O2 Oxidation Approach to Ti3C2/TiO2 for Efficient Photocatalytic Removal of Distinct Organic Pollutants in Water.

To develop versatile photocatalysts for efficient degradation of distinct organic pollutants in water is a continuous pursuit in environment remediation. Herein, we directly oxidize Ti3C2 MXene with hydrogen peroxide to produce C-doped anatase TiO2 nanowires with aggregates maintaining a layered architecture of the MXene. The Ti3C2 MXene provides a titanium source for TiO2, a carbon source for in situ C-doping, and templates for nanowire aggregates. Under UV light illumination, the optimized Ti3C2/TiO2 exhibits a reaction rate constant 1.5 times that of the benchmark P25 TiO2 nanoparticles, toward photocatalytic degradations of trace phenol in water. The mechanism study suggests that photogenerated holes play key roles on the phenol degradation, either directly oxidizing phenol molecules or in an indirect way through oxidizing first the surface hydroxyl groups. The unreacted Ti3C2 MXene, although with trace amounts, is supposed to facilitate electron transfer, which inhibits charge recombination. The unique nanostructure of layered aggregates of nanowires, abundant surface oxygen vacancies arising from the carbon doping, and probably the Ti3C2/TiO2 heterojunction guarantee the high photocatalytic efficiency toward removals of organic pollutants in water. The photocatalyst also exhibits an activity superior to, or at least comparable to, the benchmark P25 TiO2 toward photodegradations for typical persistent organic pollutants of phenol, dye molecule of rhodamine B, antibiotic of tetracycline, pharmaceutical wastewater of ofloxacin, and pesticide of N,N-dimethylformamide, when evaluated in total organic carbon removal.

Impact of preoperative factors and waiting time on post-appendectomy complications: a retrospective study.

BACKGROUND: Several factors are associated with increased postoperative complications after appendectomies. However, few studies combined these potential factors for comprehensive prediction of surgical outcomes. Whether high-risk patients benefit from a shorter waiting time for surgery remains unclear. This study aimed to explore the impact of surgical waiting time and potential risk factors on postoperative complications. METHODS: A total of 1343 patients diagnosed with acute appendicitis requiring an emergent appendectomy were included from 2013 to 2018. The preoperative risk factors associated with postoperative complications were selected and the probability of postoperative complications was calculated by multivariate logistic regression model. Patients were divided into four groups based on the risk (high & low) and time to surgery (> 12 & ≤12 hours). The odds ratios for complications were evaluated between groups. RESULTS: The selected risk factors included age, neutrophil-lymphocyte ratio, systemic inflammatory response syndrome and abdominal pain duration. Compared with low-risk patients with time to surgery ≤12 hours, high-risk patients with time to surgery > 12 hours had significant increased overall postoperative complication rate (16.85% vs. 8.16%, p = 0.002) and a trend toward increased surgical site infection rate (10.99% vs. 6.46%, p = 0.058). When operated within 12 hours, there was no difference in outcomes between high- and low-risk patients. On the other hand, time to surgery > 12 hours did not increase complication rate in low-risk patients. CONCLUSIONS: The surgical outcome may be affected by preoperative factors and time to surgery. It is suggested that high-risk patients receive appendectomy within 12 hours to avoid increased postoperative complications.

Calcitriol attenuates poly(I:C)-induced lung injury in obese mice via modulating toll-like receptor 3- and renin-angiotensin system-associated signal pathways.

This study investigated the effects of calcitriol on polyinosinic-polycytidylic acid (poly(I:C))-induced acute lung injury (ALI) and its association with Toll-like receptor 3 (TLR3) and renin-angiotensin system (RAS) signal pathways in obese mice. Normal mice were fed a high-fat diet to induce obesity. Obese mice were divided into four groups: SS group, intratracheally instilled with saline and intravenous (IV) saline injection via tail vein; SD group, instilled with saline and IV calcitriol injection; PS group, instilled with poly(I:C) and IV saline injection; and PD group, instilled with poly(I:C) and IV calcitriol injection. All mice were sacrificed 12 or 24 h after poly(I:C) stimulation. The results showed that poly(I:C) instillation led to increased production of systemic inflammatory cytokines. In the lungs, the population of macrophages decreased, while more neutrophils were recruited. TLR3-associated genes including IRF3, nuclear factor-κB, interferon-ß and phosphorylated IRF3 expression levels, were upregulated. The RAS-associated AT1R and ACE2 protein levels increased, whereas AT2R, Ang(1-7), and MasR levels decreased. Also, reduced tight junction (TJ) proteins and elevated lipid peroxide levels were observed 24 h after poly(I:C) stimulation. Compared to the PS group, the PD group exhibited reduced systemic and lung inflammatory cytokine levels, increased macrophage while decreased neutrophil percentages, downregulated TLR3-associated genes and phosphorylated IRF3, and polarized toward the RAS-AT2R/Ang(1-7)/MasR pathway in the lungs. Higher lung TJ levels and lower injury scores were also noted. These findings suggest that calcitriol treatment after poly(I:C) instillation alleviated ALI in obese mice possibly by downregulating TLR3 expression and tending toward the RAS-associated anti-inflammatory pathway.

Potential therapeutic implications of calcitriol administration and weight reduction on CD4 T cell dysregulation and renin angiotensin system-associated acute lung injury in septic obese mice.

This study investigated the effects of weight reduction and/or calcitriol administration on regulating CD4 T cell subsets and renin-angiotensin system (RAS)-associated acute lung injury (ALI) in obese mice with sepsis. Half of the mice were fed a high-fat diet for 16 weeks, half of them had high-fat diet for 12 weeks then were transferred to a low-energy diet for 4 weeks. After feeding the respective diets, cecal ligation and puncture (CLP) were performed to induce sepsis. There were four sepsis groups: OSS group, obese mice injected with saline; OSD group, obese mice given calcitriol; WSS group, mice with weight reduction and saline; WSD group, mice with weight reduction and calcitriol. Mice were sacrificed after CLP. The findings showed that CD4 T subsets distribution did not differ among the experimental groups. Calcitriol-treated groups had higher RAS-associated AT2R, MasR, ACE2, and angiopoietin 1-7 (Ang(1-7)) levels in the lungs. Also, higher tight junction proteins were noted 12 h after CLP. At 24 h post-CLP, weight reduction and/or calcitriol treatment reduced plasma inflammatory mediator production. Calcitriol-treated groups had higher CD4/CD8, T helper (Th)1/Th2 and lower Th17/regulatory T (Treg) ratios than the groups without calcitriol. In the lungs, calcitriol-treated groups had lower AT1R levels, whereas the RAS anti-inflammatory protein levels were higher than those groups without calcitriol. Lower injury scores were also noted at this time point. These findings suggested weight reduction decreased systemic inflammation. However, calcitriol administration produced a more-balanced Th/Treg distribution, upregulated the RAS anti-inflammatory pathway, and attenuated ALI in septic obese mice.

Novel Non-duct-to-Mucosa Pancreaticojejunostomy Reconstruction After Pancreaticoduodenectomy: Focus on the Occurrence of Post-pancreatectomy Hemorrhage and Intra-abdominal Abscess.

BACKGROUND: Postoperative pancreatic fistulas (POPFs) are considered inevitable in some patients after pancreaticoduodenectomy (PD), and measures to minimize their clinical impact are needed. Postpancreatectomy hemorrhage (PPH) and intra-abdominal abscess (IAA) are the most severe POPF-related complications, and concomitant leakage of contaminated intestinal content is considered the main cause. An innovative method, modified non-duct-to-mucosa pancreaticojejunostomy (TPJ), was created to prevent concomitant leakage of intestinal content, and its effectiveness was compared between two periods. METHODS: All PD patients undergoing pancreaticojejunostomy from 2012 to 2021 were included. The TPJ group consisted of 529 patients recruited from January 2018 to December 2021. A total of 535 patients receiving the conventional method (CPJ) from January 2012 to June 2017 were used as a control group. PPH and POPF were defined according to the International Study Group of Pancreatic Surgery definition, but only PPH grade C was included for analysis. An IAA was defined as a collection of postoperative fluid managed by CT-guided drainage with documental culture. RESULTS: There were no significant differences in the rate of POPF between the two groups (46.0% vs. 44.8%; p = 0.700). Furthermore, the percentages of bile in the drainage fluid in the TPJ and CPJ groups were 2.3% and 9.2%, respectively (p < 0.001). Lower proportions of PPH (0.9% vs. 6.5%; p < 0.001) and IAA (5.7% vs. 10.8%; p < 0.001) were observed for TPJ than for CPJ. On adjusted models, TPJ was significantly associated with a lower rate of PPH (odds ratio [OR] 0.132, 95% confidence interval [CI] 0.051-0.343; p < 0.001) and IAA (OR 0.514, 95% CI 0.349-0.758; p = 0.001) than CPJ. CONCLUSIONS: TPJ is feasible to be performed and is associated with a similar rate of POPF but a lower percentage of concomitant bile in the drainage fluid and subsequent rates of PPH and IAA than CPJ.

Glutamine and leucine administration attenuates muscle atrophy in sepsis.

AIMS: This study investigated whether l-glutamine (Gln) and/or l-leucine (Leu) administration could attenuate muscle atrophy in a mouse model of cecal ligation and puncture (CLP)-induced sepsis. MATERIALS AND METHODS: Septic mice were given a daily intraperitoneal injection of Gln, Leu, or Gln plus Leu, and mice were sacrificed on either day 1 or 4 after CLP. Blood and muscles were collected for analysis of amino acid contents and markers related to protein degradation, muscle regeneration, and protein synthesis. KEY FINDINGS: Leu treatment alone increased both muscle mass and total muscle protein content on day 4 after CLP. Gln administration reduced muscular Gln contents on day 1 and enhanced plasma Gln levels on day 4. Higher plasma branched-chain amino acid (BCAA) abundances and lower muscular BCAA levels were observed in Leu-treated mice on day 4. Gln and Leu individually suppressed muscle expressions of the E3 ubiquitin ligase genes, Trim63 and Fbxo32, on day 4 after CLP. As to muscle expressions of myogenic genes, both Gln and Leu upregulated Myog expression on day 1, but Leu alone enhanced Myf5 gene expression, whereas Gln plus Leu increased MyoD and Myog expression levels on day 4. Akt/mammalian target of rapamycin (mTOR) signaling was only activated by Gln and Leu when individually administered. SIGNIFICANCE: Gln and/or Leu administration reduces sepsis-induced muscle degradation and promotes myogenic gene expressions. Leu treatment alone had more-pronounced effects on maintaining muscle mass during sepsis. A combination of Gln and Leu failed to show synergistic effects on alleviating sepsis-induced muscle atrophy.

Effects of different routes and forms of vitamin D administration on CD4+ T cell homeostasis and renin-angiotensin system-associated lung injury in obese mice complicated with polymicrobial sepsis.

This study investigated the impacts of enteral cholecalciferol and/or intravenous calcitriol administration on the balance of cluster of differentiation 4-positive T cell subsets, the renin-angiotensin system (RAS), and the severity of acute lung injury (ALI) in obese mice with sepsis. Mice were fed a high-fat diet and then cecal ligation and puncture (CLP) was performed. Obese mice were divided into four sepsis groups: without vitamin D (VD) (S), with oral cholecalciferol 1 d before CLP (G), with intravenous calcitriol 1 h after CLP (V), and with both cholecalciferol before and intravenous calcitriol after CLP (GV). Mice were euthanized after CLP. The V and GV groups showed higher blood T helper (Th)1/Th2 and lower Th17/T regulatory (Treg) ratios than did the S and G groups. In the lungs, The V group had the lowest nuclear factor-κB and interleukin-1ß gene expressions among all groups 24 h post-CLP. In parallel, gene expressions of angiotensin type 2 receptor (AT2R), angiotensin-converting enzyme 2 (ACE2), and Mas receptor (MasR) were highest in the V group compared to other groups. The protein levels of MasR in the GV group and the AT2R/AT1R ratio in the V group were higher than those in the G and/or S groups. All of the VD-treated groups had lower injury scores than the S group. These findings suggest that calcitriol administration had more-pronounced impacts on regulating the homeostasis of Th/Treg cells and is prone to RAS-associated anti-inflammatory pathway in the lungs. However, both forms of VD attenuated sepsis-induced ALI in obese animals.

Coronavirus Disease Pandemic Effect on Medical-Seeking Behaviors Even in One Resource-Competent Community: A Case Controlled Study.

(1) Background: The coronavirus disease 2019 (COVID-19) pandemic had overwhelming impacts on medical services. During its initial surge, Taiwan was unique in maintaining its medical services without imposing travel restrictions, which provided an ideal environment in which to test if the fear of becoming infected with COVID-19 interfered with health-seeking behavior (HSB). We tested this hypothesis among adults with acute complicated appendicitis (ACA). (2) Methods: Adults with acute appendicitis were enrolled between 1 January and 30 June 2020 (COVID-19 period). The first two quarters of the preceding 3 years were defined as a historical control group. Outcome measures included the rate of ACA and the number of hospital stays. (3) Results: The COVID-19 era included 145 patients with acute appendicitis. Compared to the historical control (320 patients), the COVID-19 era was significantly associated with a higher length of symptom duration until presentation to the emergency room within >48 h (17.2% vs. 9.1%, p = 0.011), a higher incidence of ACA (29.7% vs. 19.4%, p = 0.014), and a longer length of hospital stays (5.0 days vs. 4.0 days, p = 0.043). The adjusted models showed that the COVID-19 period had a significant relationship with a higher rate of ACA (odds ratio (OR) = 1.87; 95% confidence interval (CI): 1.23-2.52; p = 0.008) and longer length of hospital stays (OR= 2.10; 95% CI: 0.92 to 3.31; p < 0.001). (4) Conclusions: The fear of COVID-19 may prohibit patients from seeking medical help, worsening their clinical outcomes. The surgical community should take action to provide scientific information to relive mental stress.

Effects of Different Routes and Forms of Vitamin D Administration on Mesenteric Lymph Node CD4+ T Cell Polarization and Intestinal Injury in Obese Mice Complicated with Polymicrobial Sepsis.

This study compared the efficacies of enteral cholecalciferol and/or intravenous (IV) calcitriol administration on mesenteric lymph node (MLN) cluster-of-differentiation-4-positive (CD4+) T cell distribution and intestinal barrier damage in obese mice complicated with sepsis. Mice were fed a high-fat diet for 16 weeks and then sepsis was induced by cecal ligation and puncture (CLP). Mice were divided into the following sepsis groups: without vitamin D (VD) (S); with oral cholecalciferol 1 day before CLP (G); with IV calcitriol 1 h after CLP (V); and with both cholecalciferol before and IV calcitriol after CLP (GV). All mice were sacrificed at 12 or 24 h after CLP. The findings show that the S group had a higher T helper (Th)17 percentage than the VD-treated groups at 12 h after CLP. The V group exhibited a higher Th1 percentage and Th1/Th2 ratio than the other groups at 24 h, whereas the V and GV groups had a lower Th17/regulatory T (Treg) ratio 12 h post-CLP in MLNs. In ileum tissues, the VD-treated groups had higher tight junction protein and cathelicidin levels, and higher mucin gene expression than the S group at 24 h post-CLP. Also, aryl hydrocarbon receptor (AhR) and its associated cytochrome P450 1A1 and interleukin 22 gene expressions were upregulated. In contrast, levels of lipid peroxides and inflammatory mediators in ileum tissues were lower in the groups with VD treatment after CLP. These results suggest that IV calcitriol seemed to have a more-pronounced effect on modulating the homeostasis of Th/Treg subsets in MLNs. Both oral cholecalciferol before and IV calcitriol after CLP promoted cathelicidin secretion, alleviated intestinal inflammation, and ameliorated the epithelial integrity in obese mice complicated with sepsis possibly via VD receptor and AhR signaling pathways.

Intravenous calcitriol treatment benefits the homeostasis of CD4+ T cells and attenuates kidney injury in obese mice complicated with polymicrobial sepsis.

OBJECTIVES: Sepsis is a lethal clinical condition with dysregulated cluster of differentiation (CD) 4+ T cells that leads to inflammation and multiorgan injury. Low vitamin D levels are commonly seen in patients with sepsis. Obesity is a state with oxidative stress and chronic inflammation. Both obesity and low vitamin D levels are associated with adverse outcomes in patients with sepsis. This study investigated the effects of calcitriol on CD4+ T-cell polarization and kidney injury during sepsis. METHODS: Mice were fed a high-fat diet to induce obesity. One group of obese mice served as the control group and in the other two groups (SS and SD) were performed cecal ligation and puncture (CLP) to induce sepsis. Mice in the SS group were injected with saline and those in the SD group with calcitriol 1 h after CLP via tail vein. Mice with sepsis were euthanized at 12 h and 24 h after CLP, respectively. RESULTS: Sepsis led to a decrease in circulating CD4+ T-cell percentage, and T helper (Th) 2, Th17, and regulatory T (Treg) cell percentages were upregulated. Compared with the SS group, the SD group maintained blood CD4+ T-cell levels, and were reduced the Th2 and Th17 percentages as well as the Th17:Treg ratio. Also, plasma levels of cathelicidin increased, but inflammatory chemokines and kidney injury markers were reduced. Higher arginase-1 and lower inducible nitric oxide synthase expressions in the SD group indicated M1 macrophage polarized toward the M2 type. CONCLUSIONS: These findings suggest that intravenous calcitriol administration after sepsis modulates the homeostasis of CD4+ T-cell subpopulations associated with alleviating sepsis-induced kidney injury in obese mice.

Chemical composition of smoke produced by open versus laparoscopic surgery for cholecystectomy.

BACKGROUND: Smoke produced by traditional open surgery (TOS) has long been considered hazardous to medical staff. Compared with TOS, minimally invasive surgery under carbon dioxide pneumoperitoneum is associated with a faster recovery and less wound pain. However, the impact of oxygen-deficient environment on the chemical contents of smoke has not been comprehensively assessed. METHODS: This research evaluated the chemical composition and volatile organic compound (TVOC) level in smoke produced by open cholecystectomy (OC) versus laparoscopic cholecystectomy (LC) for gallbladder diseases. Smoke samples were collected and analyzed via gas chromatography-mass spectrometry. Chemical compounds were further grouped according to molecular weight and toxicity. RESULTS: Compared with the OC, LC had significantly higher halocarbon and TVOC levels but lower cycloalkene and aldehyde levels. No halocarbons were isolated from OC specimens. When stratified based on molecular weight, LC had a bimodal pattern (i.e., high levels of small-sized [<60 Da] and large-sized [>120 Da] compounds). There was no difference in terms of toxicity types, incidence, and severity associated with detected compounds between two groups. CONCLUSION: LC is associated with a higher TVOC level and proportion of low- and high-molecular-weight organic compounds. Further strategies of evacuating these health hazards and preventing smoke leakage through trocars should be considered.

Relationship Between Symptom Distress and Fatigue Characteristics in Patients with Gastric Cancer During 1 Month after Gastrectomy.

This study's purpose was to describe changes in symptom distress and fatigue characteristics identifying which symptoms significantly impacted fatigue characteristics of patients with Gastric Cancer (GC) within 1 month after gastrectomy. A prospective longitudinal study was conducted. Patients with GC who were scheduled for gastrectomy were recruited from surgical outpatient clinics and surgery wards in northern Taiwan. Data were collected using a set of questionnaires before (T0) and 7 (T1) and 28 days (T2) after gastrectomy. Over all, 86 patients experienced mild levels of fatigue and symptom distress. The changes in worst fatigue and fatigue interference were greatest at T1. Anxiety had a significant negative effect on both worst fatigue and fatigue interference. Dry mouth, pain, and body image had significant deleterious effects on worst fatigue. The co-occurring symptoms affecting fatigue for patients with GC in the acute phase after gastrectomy should be actively assessed to ensure optimal fatigue management.

Intravenous calcitriol administration modulates mesenteric lymph node CD4+ T-cell polarization and attenuates intestinal inflammation in obese mice complicated with polymicrobial sepsis.

BACKGROUND: Sepsis is a lethal syndrome with T-cell dysregulation, imbalanced inflammatory reactions, and gastrointestinal dysfunction. Obesity coexistent with sepsis can cause more-deleterious disease outcomes. Vitamin D is a nutrient with immunomodulatory ability and helps maintain intestinal homeostasis. This study investigated treatment with calcitriol on mesenteric lymph node (MLN) CD4+ T-cell polarization and intestinal injury in obese mice with sepsis. METHODS: Mice received a high-fat diet for 10 weeks; then, mice were separated into an obese control group without sepsis and sepsis groups that underwent cecal ligation and puncture (CLP). Septic mice were subdivided into a group that was injected with saline (SS group) or a group that was injected with calcitriol (SD group) via a tail vein 1 h after CLP. Obese mice with sepsis were euthanized at 12 or 24 h post CLP. RESULTS: Sepsis resulted in increased percentages of type 2 T helper (Th2), Th17, and regulatory T (Treg) cells in MLNs. Also, inflammation-associated genes were upregulated and tight junction genes downregulated in the intestines after CLP. Compared with the SS group, the SD group exhibited reduced Th2, Th17, and Treg percentages in MLNs. Also, intestinal inflammatory chemokine expressions were reduced, whereas MUC2, ZO-1, and occludin had increased after CLP. Lower inflammatory cytokine levels in peritoneal lavage fluid in the ileum were also noted in the SD group. CONCLUSIONS: Intravenous calcitriol treatment after sepsis can elicit more-balanced CD4 T-cell subsets in lymph nodes near the intestines and alleviate intestinal inflammation and injury in obese mice complicated with sepsis.

Protective Effects of Glutamine and Leucine Supplementation on Sepsis-Induced Skeletal Muscle Injuries.

This study investigated the effects of l-glutamine (Gln) and/or l-leucine (Leu) administration on sepsis-induced skeletal muscle injuries. C57BL/6J mice were subjected to cecal ligation and puncture to induce polymicrobial sepsis and then given an intraperitoneal injection of Gln, Leu, or Gln plus Leu beginning at 1 h after the operation with re-injections every 24 h. All mice were sacrificed on either day 1 or day 4 after the operation. Blood and muscles were collected for analysis of inflammation and oxidative damage-related biomolecules. Results indicated that both Gln and Leu supplementation alleviated sepsis-induced skeletal muscle damage by reducing monocyte infiltration, calpain activity, and mRNA expression levels of inflammatory cytokines and hypoxia-inducible factor-1α. Furthermore, septic mice treated with Gln had higher percentages of blood anti-inflammatory monocytes and muscle M2 macrophages, whereas Leu treatment enhanced the muscle expressions of mitochondrion-related genes. However, there were no synergistic effects when Gln and Leu were simultaneously administered. These findings suggest that both Gln and Leu had prominent abilities to attenuate inflammation and degradation of skeletal muscles in the early and/or late phases of sepsis. Moreover, Gln promoted the switch of leukocytes toward an anti-inflammatory phenotype, while Leu treatment maintained muscle bioenergetic function.

Surface-Induced Desolvation of Hydronium Ion Enables Anatase TiO2 as an Efficient Anode for Proton Batteries.

Hydrogen ion is an attractive charge carrier for energy storage due to its smallest radius. However, hydrogen ions usually exist in the form of hydronium ion (H3O+) because of its high dehydration energy; the choice of electrode materials is thus greatly limited to open frameworks and layered structures with large ionic channels. Here, the desolvation of H3O+ is achieved by using anatase TiO2 as anodes, enabling the H+ intercalation with a strain-free characteristic. Density functional theory calculations show that the desolvation effects are dependent on the facets of anatase TiO2. Anatase TiO2 (001) surface, a highly reactive surface, impels the desolvation of H3O+ into H+. When coupled with a MnO2 cathode, the proton battery delivers a high specific energy of 143.2 Wh/kg at an ultrahigh specific power of 47.9 kW/kg. The modulation of the interactions between ions and electrodes opens new perspectives for battery optimizations.

Intravenous calcitriol administration regulates the renin-angiotensin system and attenuates acute lung injury in obese mice complicated with polymicrobial sepsis.

Calcitriol, an active form of vitamin D, has immunomodulatory and anti-inflammatory properties. Vitamin D levels have inverse correlation with sepsis outcomes and obesity may aggravate the severity of the diseases. This study administered calcitriol to investigate its impact on sepsis-induced acute lung injury (ALI) in obese mice. Mice were fed a high-fat diet to induce obesity and were randomly assigned to control or sepsis groups, which were intravenously administered either saline (SS) or calcitriol (SD). Sepsis was induced by cecal ligation and puncture (CLP). Saline or calcitriol was injected 1 h after CLP via tail vein. Mice were sacrificed at either 12 or 24 h post-CLP and survival rates were observed. The results demonstrated that sepsis caused upregulation of inflammatory mediators and downregulation of renin-angiotensin system (RAS)-associated gene expressions in the lungs of obese mice. Cluster of differentiation 68 (CD68) expression and myeloperoxidase (MPO) activities also increased. Calcitriol treatment lowered expressions of blood and lung inflammatory mediators at 12 and/or 24 h after CLP. The RAS-proinflammatory-associated angiotensin type 1 receptor (AT1R) was lower while anti-inflammatory Mas receptor and AT2R expressions were higher at 12 h after CLP than those in the SS group. In addition, the SD group exhibited lower CD68 expression and MPO activity. Lower lung injury scores and higher survival rates were also noted in the SD group. The findings suggest that calcitriol treatment after sepsis induction upregulated RAS-associated anti-inflammatory pathway and decreased immune cell infiltration, which may have alleviated the severity of ALI of obese mice.