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Feeding modes influence the gut microbiome, immune system, and intestinal barrier homeostasis in neonates; how feeding modes impact susceptibility to neonatal gastrointestinal (GI) diseases is still uncertain. Here, we investigated the impact of dam feeding (DF) and formula feeding (FF) on features of the gut microbiome and physiological inflammation during the first 2 days of postnatal development and on the susceptibility to intestinal injury related to the inflammatory state in neonatal mouse pups. 16S rRNA sequencing data revealed microbiome changes, lower α-diversity, and a distinct pattern of β-diversity including expansion of

Charging the catalytic site! Incorporation of charged arm on the phenol has tremendous increase in the catalytic activity compared to its uncharged counterpart. We also performed NMR studies to understand the mechanism of the activity.

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of preterm infants characterized by intestinal inflammation and intestinal epithelial cells (IEC) death. Evidence suggests that scattered crypt IEC apoptosis is a critical pathogenic event that subsequently leads to excessive villus necrosis in human NEC and rodent pups with experimental NEC. Necroptosis, programmed necrosis, is a proinflammatory cell death process that has been linked to several intestinal diseases. However, the critical role of necroptosis and its upstream pathways in the pathogenesis of NEC remains largely unexplored. Here, we aimed to study the linkage between scattered crypt IEC apoptosis and necroptosis during NEC development using a mouse genetic engineering approach. First, a unique triple-transgenic mouse model, 3xTg-iEAP (inducible Enterocyte specific Apoptosis Phenotype), was developed to induce IECs-specific over-expression of FasL using LoxP-Villin-Cre-mediated recombination strategy in combination with the rtTA-based regulatory system. Second, we created 3xTg-iEAPIfng-/- and 3xTg-iEAPRip3-/- mice by breeding 3xTg-iEAP with either Ifnγ knockout (KO) mice or Rip3 KO mice. The three days old neonatal pups of 3xTg-iEAP, 3xTg-iEAPIfng-/-, 3xTg-iEAPRip3-/- and littermate controls were challenged with a single dose doxycycline (Dox; 20 μg/gm, subcutaneously). Their growth was monitored on daily basis. The intestinal tissue samples were collected at different time points (8 h, 24 h, 48 h, and 72 h) and subjected to histological and qRT-PCR analysis. We confirmed that 3xTg-iEAP, 3xTg-iEAPIfng-/-, and 3xTg-iEAPRip3-/- mice developed normal, viable, and fertile, and indistinguishable from littermate controls without exposure to Dox. Treatment with Dox resulted in scattered IEC apoptosis in crypts of 3xTg-iEAP, 3xTg-iEAPIfng-/-, and 3xTg-iEAPRip3-/- mice within 8 h. Compared to littermate controls, we observed NEC-like damage with profound intestinal villus epithelial necrosis at 48 h after Dox treatment in 3xTg-iEAP mice that mimics histological features of human NEC. qRT-PCR analysis showed that the development of villus necrosis was associated with the increased expression of pro-inflammatory mediator genes and necroptosis-associated genes including Ifnγ and Rip3 in 3xTg-iEAP mice during the phase of NEC development. Interestingly, compared to 3xTg-iEAP mice, 3xTg-iEAPIfng-/- and 3xTg-iEAPRip3-/- mice displayed a lack of NEC-like incidence at 48h after Dox treatment, suggesting the crucial role of IFN-γ and RIP3 in scattered IEC apoptosis-induced NEC in our model. Taken together, the inhibition of necroptosis in IECs prevents intestinal injury during NEC. Our findings may advance knowledge in preventing or treating this devastating disorder in humans. Grants from NIH and the U.S. Department of Veterans Affairs support this work. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Being recognized as a typical pathological feature of liver diseases, apoptosis-induced hepatocyte injury leading to sterile inflammation drives a wound-healing path in vivo. We and other researchers reported that Milk fat globule-EGF factor 8 (MFGE8) preserves tissue homeostasis, protects against tissue injury and inflammation, and attenuates nonalcoholic fatty liver disease and fibrosis. However, it is unclear whether and how MFGE8 is involved in liver regeneration from hepatocyte-apoptosis-induced injury. Our aim is to study current knowledge to this extent, we created a novel triple-transgenic mouse model, an inducible hepatocyte-specific apoptosis phenotype (namely, 3XTg-iHAP), in which the inducible hepatocyte-specific FasL expression is under control of the combined LoxP-Albumin-Cre system and rtTA Tet-On regulatory element. The liver tissues from 3XTg-iHAP and their littermates were collected at 8 h, 24 h, 48 h, 72 h, and 5 D after doxycycline (Dox, 5mg/kg, s.c., single dose) treatment and subjected to histological examination, RNAScope in situ hybridization (ISH) and qRT-PCR analysis. We first confirmed that the 3XTg-iHAP mice developed normal, viable, and fertile. Upon Dox treatment, qRT-PCR confirmed FasL expression was specifically induced in the liver tissues of 3XTg-iHAP mice (male, 7 weeks) but not in their littermates. H&E sections show the induction of hepatocyte apoptosis as early as 24 h followed by apoptosis-induced sterile inflammation and injury, hepatocyte mitosis, and regeneration in the liver parenchyma of 3XTg-iHAP mice. In the ISH assay, we found that (1) In littermate control mice, Mfge8 transcripts were localized in the intrahepatic bile duct epithelial cells (i.e., cholangiocytes) within the portal area. (2) In Dox-treated 3XTg-iHAP mice, we observed a profound increase of Mfge8 gene expression in parenchymal hepatocytes of the liver featured with apoptosis-associated sterile injury. In summary, we validated a novel 3XTg-iHAP mouse liver wound-healing model. The Mfge8 gene is constitutively expressed in the bile duct epithelial cells under the normal physiological condition, while upregulated in hepatocytes in response to the apoptosis-induced injury and repair. Our results suggest that liver wound healing is associated with an increase in Mfge8 expression in hepatocytes. The underlying mechanisms of whether and how MFG-E8 promotes the liver wound healing process need to be further studied. Grants are supported by NIH and the U.S. Department of Veterans Affairs. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Intestines continue to develop after birth, and the early neonatal period is a critical phase of gastrointestinal (GI) maturation. The intestinal epithelium takes a central role in mucosal physiological functions, and it experiences renewal ability throughout life. Lgr5+ crypt base columnar stem cells (Lgr5+-CBC) and transit amplifying cells (TACs) are proliferative cells, and their physiological features can be affected by inflammation, microbiome, and environmental exposure. However, it is unclear whether and how the activity of Lgr5+-CBCs and TACs changes during postnatal development. In this study, we aimed to advance our knowledge in this aspect. Lgr5EGFP-IRES-creERT2 mice at different developmental stages including fetuses, postnatal (P) pups, and adults were subjected to BrdU/EdU dual-labeling to determine S-phase proliferative cells in the crypts and to monitor intestinal epithelial cell (IEC) migration along the crypt-villus axis for up to 72 hours. We used immunohistochemistry, click chemistry, and multi-panel RNAscope FISH to determine EdU+, BrdU+, Lgr5 +, Prom1 +, and Pcna + cells in the intestinal epithelium. We also examined the expression of multiple progenitor markers during postnatal development in the intestine using qRT-PCR. In parallel, GFP+ IECs were collected using fluorescence-activated cell sorting (FACS) and processed for qRT-PCR to determine Lgr5 expression. We found that crypt containing Lgr5+-CBC and well-organized TAC zone with EdU+ and/or Pcna + cells started to develop after birth (P0) and well-formed adult-like crypt structure at P14 in mouse pups. After this time point, the arrangement and number of Lgr5+ CBC per crypt became stable throughout adulthood. Meanwhile, these proliferative IECs were lack of this pattern during the fetal and early postnatal periods, although they were restricted to the base of the villi. Our qRT-PCR analysis showed altered expression of Lgr5 and other fetal progenitor markers (i.e. Olfm4, Axin2, Ascl2, Prom1, and Hopx) during postnatal development in the intestine. Interestingly, qRT-PCR analysis of FACS-sorted GFP+ cells (P0, P7, P14, and adult) revealed that Lgr5 expression was significantly higher in P0, suggesting CBC stem cells possess more active stemness after birth. In combined BrdU staining and EdU pulse-chase assay, we found that IEC migration was halted at P0 and P1, in which BrdU label-retaining cells resided within the crypt. Among them, a group of BrdU+/EdU+ cells showed active proliferative potential in 24 hours. In contrast, IEC migration was detected in P2, in which BrdU+ cells migrated along the crypt-villi axis, and only a few portions of BrdU label-retaining cells resided within the crypt and maintained EdU+ active proliferation. Collectively, our data indicated that the activity of Lgr5+-CBC and TACs are dynamically changed during postnatal GI development. The mechanisms underlying these alterations need further study. This work is supported by grants from NIH and U.S. Department of Veterans Affairs. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The choice of active site and support matrix decides the activity of catalyst. Any modifications on these will have a significant impact on its reactivity and selectivity. Here we have synthesised WO3 loaded boehmite and applied them for acetalization of biomass derived bulk chemical, glycerol. The well-characterized acid catalyst, exhibit a selective acetalization of glycerol with good conversions to five-membered dioxolane product. The cyclability of catalyst up to six times with retention of catalytic activity ensures the heterogeneity of the material.

Background The integral part of the definition of frailty is the outcome associated with it. Older adults at risk of frailty are in the process of becoming frail. This study looked at the clinical characteristics and outcomes of older adults at risk of frailty. Methodology The study population was selected from outpatient department of the geriatric medicine department in a tertiary care hospital. Older adults identified as at risk of frailty were assessed at baseline and then followed up after 1 year for the composite primary outcome of death, falls, hospitalization, and self‐rated poor quality of life in the follow‐up period. Results The study included 324 older adults who had completed 1‐year follow up. Mean (SD) age was 74.49 (4.58) years, and males were 241 (74.15%). Frail and pre‐frail at baseline among the study population were 31.17% and 61.11%, respectively. The primary outcome occurred in 43 (13.27%) patients. Poor baseline IADL was significantly associated with primary outcome at the end of 1 year. Conclusion An unfavorable outcome in older adults at risk of frailty was significantly higher and independent of their baseline frailty status. Poor baseline IADL value may be considered as a predictor for primary outcome at 1 year of follow up., The integral part of the definition of frailty is the outcome associated with it. Older adults at risk of frailty are in the process of becoming frail. This study looked at the clinical characteristics and outcomes of older adults at risk of frailty. The study population was selected from outpatient department of the geriatric medicine department in a tertiary care hospital. Older adults identified as at risk of frailty were assessed at baseline and then followed up after 1 year for the composite primary outcome of death, falls, hospitalization, and self‐rated poor quality of life in the follow‐up period. The study included 324 older adults who had completed 1 year of follow up. Mean (SD) age was 74.49 (4.58) years, and males were 241 (74.15%). Frail and pre‐frail at baseline among the study population were 31.17% and 61.11%, respectively. The primary outcome occurred in 43 (13.27%) patients. Poor baseline IADL was significantly associated with primary outcome at the end of 1 year. An unfavorable outcome in older adults at risk of frailty was significantly higher and independent of their baseline frailty status. Poor baseline IADL value may be considered as a predictor for primary outcome at 1 year of follow up.

Among urological tumors, renal cell carcinoma (RCC) is the third-highest mortality rate tumor, and 20%–30% of RCC patients present with metastases at the time of diagnosis. While the treatment of RCC has been improved over the last few years, its mortality stays high. Y-box binding protein 1 (YBX1) is a well-known oncoprotein that has tumor-promoting functions. YBX1 is widely considered to be an attractive therapeutic target in cancer. To develop novel therapeutics to target YBX1, it is of great importance to understand how YBX1 is finely regulated in cancer. Our previous studies showed that YBX1 in RCC cells significantly promoted cell adhesion, migration, and invasion. However, the role of YBX1 in RCC cells apoptosis has not been reported. In this study, we investigated the effect of YBX1 on cell apoptosis and elucidated the mechanisms involved. Results showed that YBX1 regulated RCC cells apoptosis and reactive oxygen species (ROS) generation via Kindlin-2. These findings indicated that YBX1 inhibited RCC cells apoptosis and may serve as a candidate RCC prognostic marker and a potential therapeutic target. Abbreviations: RCC: Renal cell carcinoma; YBX1: Y-box binding protein 1; ROS: Reactive oxygen species; ccRCC: Clear cell renal cell carcinoma; mccRCC: Metastatic clear cell renal cell carcinoma; G3BP1: Ras-GTPase activating protein SH3 domain-binding proteins 1; SPP1: Secreted phosphoprotein 1; NF-κB: Nuclear factor kappa beta; ECM: Extracellular matrix; EMT: Epithelial-mesenchymal transition; PYCR1: Pyrroline-5-carboxylate reductase 1; MEM: Eagle’s Minimum Essential Medium; DMEM: Dulbecco’s modified Eagle medium; FBS: Fetal bovine serum; PCR: Polymerase chain reaction; shRNA: Short hairpin RNA; siRNA: Small interfering RNA; BSA: Bovine serum albumin; DCFH-DA: 2,7-Dichlorodihydrofluorescein diacetate; FITC: Fluorescein isothiocyanate; PI: Propidium iodide

Thermoelectric (TE) materials could provide an efficient means for recovering waste heat energy if a low cost, scalable, and high figure-of-merit material could be fabricated. Here, we report, for the first time, a wet ball-milling method to achieve high-performance two-dimensional (2D) semi-metallic TiS2 nanoplatelets. TiO2 is milled, annealed, and sintered with sulfur under high pressure. The addition of a small amount of sulfur (S) powder during the annealing period prevents sulfur deficiency in the sintered compact, resulting in the formation of a near-stoichiometric TiS2 composition. The formation of 2D TiS2 nanoplatelets was confirmed by X-ray diffraction, field emission scanning electron microscopy with energy-dispersive spectroscopy, and X-ray photoelectron spectroscopy. The TE properties were measured in the temperature range of 25–100 °C. Further, we obtain that the prepared TiS2 has as high figure of merit as 0.35 at 100 °C. Novel wet ball mill processing strategies for the development of high-performance 2D materials such as TiS2 make it possible to incorporate these materials for scaled-up device fabrication.

Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin’s lymphoma (NHL). Usually, it presents as expanding mass in the neck or abdomen but can present in unusual ways as an extranodal disease, with multiorgan involvement. Appropriate suspicion and workup can lead to early diagnosis to initiate early treatment, but it comes with multiple challenges, in case of older frail population. Herewith, we are reporting our patient, a 63-year-old frail older woman presented as multiple cranial nerve palsy and renal impairment at presentation.

Controlling the product selectivity of a ring-opening hydrolysis reaction remains a great challenge with mineral acids and to an extent with homogeneous catalysts. In addition, even trace amounts of metal impurities in a bioactive product hinder the reaction progress. This has necessitated the development of robust and metal-free catalysts to offer an alternative sustainable route. We report a nitrogen-rich sulfonated carbon as a catalyst derived from an inexpensive precursor for the synthesis of bioactive vicinal diols of spiro-oxindole derivatives. The well-characterized catalyst shows wide generality with different electronic and steric substituents in the substrates under mild reaction conditions. Hot filtration test confirms no leaching of the acid moiety and the catalyst could be reused for four cycles with retention of activities.

Stoichiometric carbon dioxide reduction to highly reduced C1 molecules, such as formic acid (2e- ), formaldehyde (4e- ), methanol (6e- ) or even most-reduced methane (8e- ), has been successfully achieved by using organosilanes, organoboranes, and frustrated Lewis Pairs (FLPs) in the presence of suitable catalyst. The development of renewable organohydride compounds could be the best alternative in this regard as they have shown promise for the transfer of hydride directly to CO2 . Reduction of CO2 by two electrons and two protons to afford formic acid by using renewable organohydride molecules has recently been investigated by various groups. However, catalytic CO2 reduction to ≥2e- -reduced products by using renewable organohydride-based molecules has rarely been explored. This Minireview summarizes important findings in this regard, encompassing both stoichiometric and catalytic CO2 reduction.

Isolated pleural effusion is a rare manifestation of filariasis that mimics tuberculosis, especially in endemic regions. We describe a case of lymphocytic and exudative pleural effusion showing microfilaria on pleural fluid cytology. A retrospective review of all cases of filarial pleural effusion reported after 2000 was conducted to evaluate the association between filariasis and pleural effusion as well as to screen the features that can help in accurate detection of these patients. The analysis suggested a causal association between the parasite and the development of pleural effusion with a high sensitivity of pleural fluid cytology for diagnosis.

Non-redox carbon dioxide utilization through cycloaddition of CO2 to epoxides offers great promise but suffers from lack of heterogeneous catalysts that don’t need additives or pressure. Here we report a systematic post-synthetic modification procedure on a highly porous hydrocarbon framework for efficient grafting of quaternary ammonium salts. The active sites were tuned and characterized while maintaining the porous structure. The metal free and cost-effective catalysts showed quantitative selectivity and very high conversion yields in atmospheric pressure catalysis for cyclic carbonate formation from CO2 and epoxides. The reaction proceeded without additives or co-catalysts, and tolerant for a wide substrate scope. We found that the steric hindrance of the alkyl units on ammonium salts affect microporosity, CO2 binding and the kinetics of cycloaddition reactions. The catalysts were also recyclable, an attractive prerequisite for industrial implementation.

Urban mining of precious metals from electronic waste, such as printed circuit boards (PCB), is not yet feasible because of the lengthy isolation process, health risks, and environmental impact. Although porous polymers are particularly effective toward the capture of metal contaminants, those with porphyrin linkers have not yet been considered for precious metal recovery, despite their potential. Here, we report a porous porphyrin polymer that captures precious metals quantitatively from PCB leachate even in the presence of 63 elements from the Periodic Table. The nanoporous polymer is synthesized in two steps from widely available monomers without the need for costly catalysts and can be scaled up without loss of activity. Through a reductive capture mechanism, gold is recovered with 10 times the theoretical limit, reaching a record 1.62 g/g. With 99% uptake taking place in the first 30 min, the metal adsorbed to the porous polymer can be desorbed rapidly and reused for repetitive batches. Density functional theory (DFT) calculations indicate that energetically favorable multinuclear-Au binding enhances adsorption as clusters, leading to rapid capture, while Pt capture remains predominantly at single porphyrin sites.

The construction of sophisticated molecular architectures from chemical subunits requires careful selection of the spacers, precise synthetic strategies, and substantial efforts. Here, we report a series of binuclear double-stranded helicates synthesized from different combinations of pyridyl hydrazone-based multidentate ligands (H21, H22, H23) by increasing the methylene spacer and transition metals (Co, Ni, and Zn). The ligands H21 (N′1,N′3-bis((E)-pyridin-2-ylmethylene)malonohydrazide), H22 (N′1,N′4-bis((E)-pyridin-2-ylmethylene)succinohydrazide), and H23 (N′1,N′5-bis((E)-pyridin-2-ylmethylene)glutarohydrazide) and their respective complexes with Co, Ni, and Zn were obtained. Single-crystal X-ray diffraction studies of these binuclear metallohelicates confirm the double-stranded helical structure of the complexes derived from H22. The set of helicates Co-1, Co-2, and Co-3; Ni-1, Ni-2, and Ni-3; and Zn-1, Zn-2, and Zn-3 were investigated for its catalytic activity in the cyclic carbonate formation reaction. Intriguingly, among the synthesized catalyst, Co-1 was found to be better in terms of conversions with the calculated TOF (turnover frequency) of 128/h. The catalytic performance was significantly improved by adding 0.2 mmol of tetrabutylammonium bromide by achieving 76% conversion in 30 min, with the observed TOF of 15,934 h–1/molecule and 7967 h–1/Co center. The results obtained herein show that the double-stranded helicates are effective catalysts for converting both terminal and non-terminal epoxides into their corresponding cyclic carbonates. The striking feature of this catalytic protocol lies in demonstrating the catalytic activity for the conversion of diol to cyclic carbonate, and the detailed kinetic experiments tempted us to propose a tentative reaction mechanism for this conversion.

Overcoming surface defects Dry reforming of methane with carbon dioxide creates a mixture of hydrogen and carbon monoxide—synthesis gas—which can be converted into liquid fuels. However, heterogeneous catalysts for this reaction are prone to deactivation through unwanted carbon deposition (coking) and loss of surface area of adsorbed metal nanoparticles through agglomeration (sintering). Y. Song et al. used highly crystalline fumed magnesium oxide to support molybdenumdoped nickel nanoparticle catalysts (see the Perspective by Chen and Xu). On heating, the nanoparticles migrated on the oxide surface to step edges to form larger, highly stable nanoparticles. This process also passivated sites for coking on the oxide to produce a catalyst with high activity and longevity at 800°C. Science , this issue p. 777 ; see also p. 737

Background Falls are one of the major causes of disability in older people. A wide range of risk factors for falls are described according to setting – inpatient, nursing homes and community. The aim of this study was to identify the risk factors for falls in an outpatient setting. Methods In this cross‐sectional observational study, 160 consenting subjects were enrolled randomly, from the Geriatric Medicine outpatient department, All India Institute of Medical Sciences, New Delhi, India. Non‐ambulatory, seriously ill subjects were excluded. The subjects underwent brief evaluation including falls and geriatric assessment. They were grouped into fallers and non‐fallers. A multivariable logistic regression analysis was used to identify the factors associated with falls. Results The prevalence of falls was 23.75% (38/160). Women were proportionately higher (26.31%) in the fallers group vis‐à‐vis 19.67% in the non‐fallers group. After multivariate analysis, opioids (odds ratio [OR] 5.24 [95% CI, 2.0 18‐13.611]), vision impairment (OR 2.71 [95% CI, 1.050‐07.011]), fear of falling (OR 3.17 [95% CI, 1.167‐08.629]), instrumental activity of daily living (IADL) impairment (OR 3.41 [95% CI, 1.251‐09.301]), anti‐anginal medications (OR 8.90 [95% CI, 0.997‐79.564]) and self‐employment (OR 5.37 [95% CI, 1.058‐27.329]) were associated with falls. Adequate nutrition (OR 0.82 [95% CI, 0.688‐00.976]) and caregiver support (OR 0.46 [95% CI, 0.275‐00.801]) were protective of falls. Conclusion We identified the multi‐factorial etiology of falls. Patients having any of the above risk factors should undergo detailed fall risk assessment and preventive measures afterwards.

A highly regioselective, solvent-free and montmorillonite K10 clay-catalyzed domino process with an unprecedented ring-closing C–C bond-formation reaction is described for the synthesis of a new class of 1,3,4-trisubstituted and 1,4-disubstituted pyrazole derivatives. The reaction proceeded via nucleophilic attack of enamine from an intermediate on the β-carbon of an amino acrylate. Experimental outcomes clearly revealed that organic solvents had an adverse effect upon pyrazole formation, and that an oxidative condition in the presence of the reusable clay favored formation of the 1,3,4-trisubstituted pyrazole. The clay in the presence of a N-bromosuccinamide catalyst gave the 1,4-disubstituted pyrazole after pyrolytic cleavage at elevated temperature.