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Recent studies indicate that heat stress pathophysiology is associated with intestinal barrier dysfunction, local and systemic inflammation, and gut dysbiosis. However, inconclusive results and a poor description of tissue-specific changes must be addressed to identify potential intervention targets against heat stress illness in growing calves. Therefore, the objective of this study was to evaluate components of the intestinal barrier, pro- and anti-inflammatory signals, and microbiota community composition in Holstein bull calves exposed to heat stress. Animals (mean age = 12 wk old; mean body weight = 122 kg) penned individually in temperature-controlled rooms were assigned to (1) thermoneutral conditions (constant room temperature at 19.5°C) and restricted offer of feed (TNR, n = 8), or (2) heat stress conditions (cycles of room temperatures ranging from 20 to 37.8°C) along with ad libitum offer of feed (HS, n = 8) for 7 d. Upon treatment completion, sections of the jejunum, ileum, and colon were collected and snap-frozen immediately to evaluate gene and protein expression, cytokine concentrations, and myeloperoxidase activity. Digesta aliquots of the ileum, colon, and rectum were collected to assess bacterial communities. Plasma was harvested on d 2, 5, and 7 to determine cytokine concentrations. Overall, results showed a section-specific effect of HS on intestinal integrity. Jejunal mRNA expression of TJP1 was decreased by 70.9% in HS relative to TNR calves. In agreement, jejunal expression of heat shock transcription factor-1 protein, a known tight junction protein expression regulator, decreased by 48% in HS calves. Jejunal analyses showed that HS decreased concentrations of IL-1α by 36.6% and tended to decrease the concentration of IL-17A. Conversely, HS elicited a 3.5-fold increase in jejunal concentration of anti-inflammatory IL-36 receptor antagonist. Plasma analysis of pro-inflammatory cytokines showed that IL-6 decreased by 51% in HS relative to TNR calves. Heat stress alteration of the large intestine bacterial communities was characterized by increased genus Butyrivibrio_3 , a known butyrate-producing organism, and changes in bacteria metabolism of energy and AA. A strong positive correlation between the rectal temperature and pro-inflammatory Eggerthii spp. was detected in HS calves. In conclusion, this work indicates that HS impairs the intestinal barrier function of jejunum. The pro- and anti-inflammatory signal changes may be part of a broader response to restore intestinal homeostasis in jejunum. The changes in large intestine bacterial communities favoring butyrate-producing organisms (e.g., Butyrivibrio spp.) may be part of a successful response to maintain the integrity of the colonic mucosa of HS calves. The alteration of intestinal homeostasis should be the target for heat stress therapies to restore biological functions, and, thus highlights the relevance of this work. [ABSTRACT FROM AUTHOR]

Radiation therapy plays a key role in the multimodality management of gynecologic malignancies and involves advanced, conformal treatment delivery techniques that are enhanced with high quality on-board imaging. Magnetic resonance imaging–guided linear accelerators (MR-Linacs) integrate real-time MR imaging with radiation treatment delivery to enable targeting MRI targets and daily adaptive treatment. Since MR imaging allows for improved soft tissue resolution over CT, particularly for gynecologic malignancies, the benefits of adaptive MR image guidance can lead to improved tumor coverage and decreased toxicity. Here, we report clinical outcomes for patients with gynecologic cancers treated with definitive radiation therapy using an MR-Linac. We identified a retrospective cohort of patients with gynecologic cancers who received at least 5 fractions on the MR-Linac as part of a definitive course of therapy. These patients were treated at a tertiary academic cancer center from August 2019 to October 2023. MRL treatment was recommended for patients with gross disease, critical adjacent structures and not candidates for brachytherapy based on disease extent or co-morbidities. Adverse events were assessed using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. The Kaplan-Meier method was used to estimate local progression free survival (PFS). We identified 38 patients, with median follow up time of 33.6 months from the initiation of radiation therapy. Median age was 58 years at time of current disease diagnosis. The number of fractions on the MR-Linac ranged from 5 to 28, at a median dose of 230 cGy per fraction. Final prescribed MR-Linac dose ranged from 1000 to 6160 cGy. Patients were diagnosed with uterine cancer (55.2%), cervical cancer (15.8%), ovarian cancer (7.9%) or other gynecologic cancer (21.1%). 57.9% had recurrent cancers while the remainder were treated definitively for primary disease. Twenty-nine (76.3%) patients received an adapt to position for any fraction, and 12 (31.6%) required an adapt to shape for any fraction. Targets include vaginal cuff alone (12, 31.6%), lymph node (4, 10.5%) vaginal cuff plus a node (4, 10.5%), or other pelvic mass (15, 39.5%). There were no reported treatment-related grade 3+ adverse events. The percentage of patients who had complete response on PET was 55.2%. For all patients, local progression-free survival at 12 and 24 months was 100% and 96.4%, respectively. Use of the MR-Linac for definitive treatment of high-risk gynecologic cancers is clinically feasible and effective, with a favorable toxicity profile. Further studies are warranted to confirm these findings in a larger population and identify patients who may benefit most from this technology. [ABSTRACT FROM AUTHOR]

The terrestrial ecosystem in China mitigates 21%-45% of the national contemporary fossil fuel CO 2 emissions every year. Maintaining and strengthening the land carbon sink is essential for reaching China's target of carbon neutrality. However, this sink is subject to large uncertainties due to the joint impacts of climate change, air pollution, and human activities. Here, we explore the potential of strengthening land carbon sink in China through anthropogenic interventions, including forestation, ozone reduction, and litter removal, taking advantage of a well-validated dynamic vegetation model and meteorological forcings from 16 climate models. Without anthropogenic interventions, considering Shared Socioeconomic Pathways (SSP) scenarios, the land sink is projected to be 0.26-0.56 Pg C a -1 at 2060, to which climate change contributes 0.06-0.13 Pg C a -1 and CO 2 fertilization contributes 0.08-0.44 Pg C a -1 with the stronger effects for higher emission scenarios. With anthropogenic interventions, under a close-to-neutral emission scenario (SSP1-2.6), the land sink becomes 0.47-0.57 Pg C a -1 at 2060, including the contributions of 0.12 Pg C a -1 by conservative forestation, 0.07 Pg C a -1 by ozone pollution control, and 0.06-0.16 Pg C a -1 by 20% litter removal over planted forest. This sink can mitigate 90%-110% of the residue anthropogenic carbon emissions in 2060, providing a solid foundation for the carbon neutrality in China., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)

Perovskite light-emitting diodes (PeLEDs) exhibit remarkable potential in the field of displays and solid-state lighting. However, blue PeLEDs, a key element for practical applications, still lag behind their green and red counterparts, due to a combination of strong nonradiative recombination losses and unoptimized device structures. In this report, we propose a buried interface modification strategy to address these challenges by focusing on the bottom-hole transport layer (HTL) of the PeLEDs. On the one hand, a multifunctional molecule, aminoacetic acid hydrochloride (AACl), is introduced to modify the HTL/perovskite interface to regulate the perovskite crystallization. Experimental investigations and theoretical calculations demonstrate that AACl can effectively reduce the nonradiative recombination losses in bulk perovskites by suppressing the growth of low-n perovskite phases and also the losses at the bottom interface by passivating interfacial defects. On the other hand, a self-assembly nanomesh structure is ingeniously developed within the HTLs. This nanomesh structure is meticulously crafted through the blending of poly-(9,9-dioctyl-fluorene-co-N-(4-butyl phenyl) diphenylamine) and poly (n-vinyl carbazole), significantly enhancing the light outcoupling efficiency in PeLEDs. As a result, our blue PeLEDs achieve remarkable external quantum efficiencies, 20.4% at 487 nm and 12.5% at 470 nm, which are among the highest reported values. Our results offer valuable insights and effective methods for achieving high-performance blue PeLEDs., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)

TRIM71 is an RNA-binding protein with ubiquitin ligase activity. Numerous functions of mammalian TRIM71, including cell cycle regulation, embryonic stem cell (ESC) self-renewal, and reprogramming of pluripotent stem cells, are related to its RNA-binding property. We previously reported that a long noncoding RNA (lncRNA) Trincr1 interacts with mouse TRIM71 (mTRIM71) to repress FGF/ERK pathway in mouse ESCs (mESCs). Herein, we identify an RNA motif specifically recognized by mTRIM71 from Trincr1 RNA, and solve the crystal structure of the NHL domain of mTRIM71 complexed with the RNA motif. Similar to the zebrafish TRIM71, mTRIM71 binds to a stem-loop structured RNA fragment of Trincr1, and an adenosine base at the loop region is crucial for the mTRIM71 interaction. We map similar hairpin RNAs preferably bound by TRIM71 in the mRNA UTRs of the cell-cycle related genes regulated by TRIM71. Furthermore, we identify key residues of mTRIM71, conserved among mammalian TRIM71 proteins, required for the RNA-binding property. Single-site mutations of these residues significantly impair the binding of TRIM71 to hairpin RNAs in vitro and to mRNAs of Cdkn1a/p21 and Rbl2/p130 in mESCs. Furthermore, congenital hydrocephalus (CH) specific mutation of mTRIM71 impair its binding to the RNA targets as well. These results reveal molecular mechanism behind the recognition of RNA by mammalian TRIM71 and provide insights into TRIM71 related diseases., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2023 Science China Press. Published by Elsevier B.V. All rights reserved.)