Search

Reactor neutrino experiments play a crucial role in advancing our knowledge of neutrinos. In this Letter, the evolution of the flux and spectrum as a function of the reactor isotopic content is reported in terms of the inverse-beta-decay yield at Daya Bay with 1958 days of data and improved systematic uncertainties. These measurements are compared with two signature model predictions: the Huber-Mueller model based on the conversion method and the SM2018 model based on the summation method. The measured average flux and spectrum, as well as the flux evolution with the ^{239}Pu isotopic fraction, are inconsistent with the predictions of the Huber-Mueller model. In contrast, the SM2018 model is shown to agree with the average flux and its evolution but fails to describe the energy spectrum. Altering the predicted inverse-beta-decay spectrum from ^{239}Pu fission does not improve the agreement with the measurement for either model. The models can be brought into better agreement with the measurements if either the predicted spectrum due to ^{235}U fission is changed or the predicted ^{235}U, ^{238}U, ^{239}Pu, and ^{241}Pu spectra are changed in equal measure.

We present a new determination of the smallest neutrino mixing angle θ_{13} and the mass-squared difference Δm_{32}^{2} using a final sample of 5.55×10^{6} inverse beta-decay (IBD) candidates with the final-state neutron captured on gadolinium. This sample is selected from the complete dataset obtained by the Daya Bay reactor neutrino experiment in 3158 days of operation. Compared to the previous Daya Bay results, selection of IBD candidates has been optimized, energy calibration refined, and treatment of backgrounds further improved. The resulting oscillation parameters are sin^{2}2θ_{13}=0.0851±0.0024, Δm_{32}^{2}=(2.466±0.060)×10^{-3}  eV^{2} for the normal mass ordering or Δm_{32}^{2}=-(2.571±0.060)×10^{-3}  eV^{2} for the inverted mass ordering.

This Letter reports the first measurement of high-energy reactor antineutrinos at Daya Bay, with nearly 9000 inverse beta decay candidates in the prompt energy region of 8-12 MeV observed over 1958 days of data collection. A multivariate analysis is used to separate 2500 signal events from background statistically. The hypothesis of no reactor antineutrinos with neutrino energy above 10 MeV is rejected with a significance of 6.2 standard deviations. A 29% antineutrino flux deficit in the prompt energy region of 8-11 MeV is observed compared to a recent model prediction. We provide the unfolded antineutrino spectrum above 7 MeV as a data-based reference for other experiments. This result provides the first direct observation of the production of antineutrinos from several high-Q_{β} isotopes in commercial reactors.

A joint determination of the reactor antineutrino spectra resulting from the fission of ^{235}U and ^{239}Pu has been carried out by the Daya Bay and PROSPECT Collaborations. This Letter reports the level of consistency of ^{235}U spectrum measurements from the two experiments and presents new results from a joint analysis of both data sets. The measurements are found to be consistent. The combined analysis reduces the degeneracy between the dominant ^{235}U and ^{239}Pu isotopes and improves the uncertainty of the ^{235}U spectral shape to about 3%. The ^{235}U and ^{239}Pu antineutrino energy spectra are unfolded from the jointly deconvolved reactor spectra using the Wiener-SVD unfolding method, providing a data-based reference for other reactor antineutrino experiments and other applications. This is the first measurement of the ^{235}U and ^{239}Pu spectra based on the combination of experiments at low- and highly enriched uranium reactors.

The prediction of reactor antineutrino spectra will play a crucial role as reactor experiments enter the precision era. The positron energy spectrum of 3.5 million antineutrino inverse beta decay reactions observed by the Daya Bay experiment, in combination with the fission rates of fissile isotopes in the reactor, is used to extract the positron energy spectra resulting from the fission of specific isotopes. This information can be used to produce a precise, data-based prediction of the antineutrino energy spectrum in other reactor antineutrino experiments with different fission fractions than Daya Bay. The positron energy spectra are unfolded to obtain the antineutrino energy spectra by removing the contribution from detector response with the Wiener-SVD unfolding method. Consistent results are obtained with other unfolding methods. A technique to construct a data-based prediction of the reactor antineutrino energy spectrum is proposed and investigated. Given the reactor fission fractions, the technique can predict the energy spectrum to a 2% precision. In addition, we illustrate how to perform a rigorous comparison between the unfolded antineutrino spectrum and a theoretical model prediction that avoids the input model bias of the unfolding method.

The establishment of a possible connection between neutrino emission and gravitational-wave (GW) bursts is important to our understanding of the physical processes that occur when black holes or neutron stars merge. In the Daya Bay experiment, using the data collected from December 2011 to August 2017, a search was performed for electron-Antineutrino signals that coincided with detected GW events, including GW150914, GW151012, GW151226, GW170104, GW170608, GW170814, and GW170817. We used three time windows of 10, 500, and 1000 s relative to the occurrence of the GW events and a neutrino energy range of 1.8 to 100 MeV to search for correlated neutrino candidates. The detected electron-Antineutrino candidates were consistent with the expected background rates for all the three time windows. Assuming monochromatic spectra, we found upper limits (90% confidence level) of the electron-Antineutrino fluence of (1.13-2.44)×1011 cm-2 at 5 MeV to 8.0×107 cm-2 at 100 MeV for the three time windows. Under the assumption of a Fermi-Dirac spectrum, the upper limits were found to be (5.4-7.0)×109 cm-2 for the three time windows.

BackgroundMultiple lines of evidence suggest the presence of altered neuroimmune processes in patients with schizophrenia (Sz) and severe mood disorders. Recent studies using a novel free water diffusion tensor imaging (FW DTI) approach, proposed as a putative biomarker of neuroinflammation, atrophy, or edema, have shown significantly increased FW in patients with Sz. However no studies to date have investigated the longitudinal stability of FW alterations during the early course of psychosis, nor have studies focused separately on FE psychosis patients with Sz or bipolar disorder (BD) with psychotic features.MethodsThe current study included 188 participants who underwent diffusion magnetic resonance imaging scanning at baseline. Sixty-four participants underwent follow-up rescanning after 12 months. DTI-based alterations in patients were calculated using voxelwise tract-based spatial statistics and region of interest analyses.ResultsPatients with FE psychosis, both Sz and BD, exhibited increased FW at illness onset which remained unchanged over the 12-month follow-up period. Preliminary analyses suggested that antipsychotic medication exposure was associated with higher FW in gray matter that reached significance in the BD group. Higher FW in white matter correlated with negative symptom severity.ConclusionsOur results support the presence of elevated FW at the onset of psychosis in both Sz and BD, which remains stable during the early course of the illness, with no evidence of either progression or remission.

The prediction of reactor antineutrino spectra will play a crucial role asreactor experiments enter the precision era. The positron energy spectrum of3.5 million antineutrino inverse beta decay reactions observed by the Daya Bayexperiment, in combination with the fission rates of fissile isotopes in thereactor, is used to extract the positron energy spectra resulting from thefission of specific isotopes. This information can be used to produce aprecise, data-based prediction of the antineutrino energy spectrum in otherreactor antineutrino experiments with different fission fractions than DayaBay. The positron energy spectra are unfolded to obtain the antineutrino energyspectra by removing the contribution from detector response with the Wiener-SVDunfolding method. Consistent results are obtained with other unfolding methods.A technique to construct a data-based prediction of the reactor antineutrinoenergy spectrum is proposed and investigated. Given the reactor fissionfractions, the technique can predict the energy spectrum to a 2% precision. Inaddition, we illustrate how to perform a rigorous comparison between theunfolded antineutrino spectrum and a theoretical model prediction that avoidsthe input model bias of the unfolding method.

Searches for electron antineutrino, muon neutrino, and muon antineutrino disappearance driven by sterile neutrino mixing have been carried out by the Daya Bay and MINOS+ collaborations. This Letter presents the combined results of these searches, along with exclusion results from the Bugey-3 reactor experiment, framed in a minimally extended four-neutrino scenario. Significantly improved constraints on the θ_{μe} mixing angle are derived that constitute the most constraining limits to date over five orders of magnitude in the mass-squared splitting Δm_{41}^{2}, excluding the 90% C.L. sterile-neutrino parameter space allowed by the LSND and MiniBooNE observations at 90% CL_{s} for Δm_{41}^{2}

A high precision calibration of the nonlinearity in the energy response of the Daya Bay Reactor Neutrino Experiment's antineutrino detectors is presented in detail. The energy nonlinearity originates from the particle-dependent light yield of the scintillator and charge-dependent electronics response. The nonlinearity model is constrained by γ calibration points from deployed and naturally occurring radioactive sources, the β spectrum from 12B decays, and a direct measurement of the electronics nonlinearity with a new flash analog-to-digital converter readout system. Less than 0.5% uncertainty in the energy nonlinearity calibration is achieved for positrons of kinetic energies greater than 1 MeV.

This Letter reports the first extraction of individual antineutrino spectra from ^{235}U and ^{239}Pu fission and an improved measurement of the prompt energy spectrum of reactor antineutrinos at Daya Bay. The analysis uses 3.5×10^{6} inverse beta-decay candidates in four near antineutrino detectors in 1958 days. The individual antineutrino spectra of the two dominant isotopes, ^{235}U and ^{239}Pu, are extracted using the evolution of the prompt spectrum as a function of the isotope fission fractions. In the energy window of 4-6 MeV, a 7% (9%) excess of events is observed for the ^{235}U (^{239}Pu) spectrum compared with the normalized Huber-Mueller model prediction. The significance of discrepancy is 4.0σ for ^{235}U spectral shape compared with the Huber-Mueller model prediction. The shape of the measured inverse beta-decay prompt energy spectrum disagrees with the prediction of the Huber-Mueller model at 5.3σ. In the energy range of 4-6 MeV, a maximal local discrepancy of 6.3σ is observed.

This Letter reports the first extraction of individual antineutrino spectra from ^{235}U and ^{239}Pu fission and an improved measurement of the prompt energy spectrum of reactor antineutrinos at Daya Bay. The analysis uses 3.5×10^{6} inverse beta-decay candidates in four near antineutrino detectors in 1958 days. The individual antineutrino spectra of the two dominant isotopes, ^{235}U and ^{239}Pu, are extracted using the evolution of the prompt spectrum as a function of the isotope fission fractions. In the energy window of 4-6 MeV, a 7% (9%) excess of events is observed for the ^{235}U (^{239}Pu) spectrum compared with the normalized Huber-Mueller model prediction. The significance of discrepancy is 4.0σ for ^{235}U spectral shape compared with the Huber-Mueller model prediction. The shape of the measured inverse beta-decay prompt energy spectrum disagrees with the prediction of the Huber-Mueller model at 5.3σ. In the energy range of 4-6 MeV, a maximal local discrepancy of 6.3σ is observed.

The Daya Bay Collaboration responds to comments posted by S. Parke and R.Zukanovich Funchal regarding our use of Delta(m^2_ee).

Episodic memory deficits are consistently documented as a core aspect of cognitive dysfunction in schizophrenia patients, present from the onset of the illness and strongly associated with functional disability. Over the past decade, research using approaches from experimental cognitive neuroscience revealed disproportionate episodic memory impairments in schizophrenia (Sz) under high cognitive demand relational encoding conditions and relatively unimpaired performance under item-specific encoding conditions. These specific deficits in component processes of episodic memory reflect impaired activation and connectivity within specific elements of frontal-medial temporal lobe circuits, with a central role for the dorsolateral prefrontal cortex (DLPFC), relatively intact function of ventrolateral prefrontal cortex and variable results in the hippocampus. We propose that memory deficits can be understood within the broader context of cognitive deficits in Sz, where impaired DLPFC-related cognitive control has a broad impact across multiple cognitive domains. The therapeutic implications of these findings are discussed.

A search for a time-varying νe signal was performed with 621 days of data acquired by the Daya Bay Reactor Neutrino Experiment over 704 calendar days. The time spectrum of the measured νe flux normalized to its prediction was analyzed with a Lomb-Scargle periodogram, which yielded no significant signal for periods ranging from 2 hours to nearly 2 years. The normalized time spectrum was also fit for a sidereal modulation under the Standard Model Extension (SME) framework to search for Lorentz and CPT violation (LV-CPTV). Limits were obtained for all six flavor pairs ēμ,ēτ, μτ, ēē,μμ and ττ by fitting them one at a time, constituting the first experimental constraints on the latter three. Daya Bay's high statistics and unique layout of multiple directions from three pairs of reactors to three experimental halls allowed the simultaneous constraint of individual SME LV-CPTV coefficients without assuming others contribute negligibly, a first for a neutrino experiment.

Methanol dehydrogenation (MD) is highly valuable in hydrogen energy production, and the introduction of nonmetals has received much attention to improve the activity and stability of the MD catalysts, but the understanding of the role of non-metallic elements in catalyzing the MD reaction is rather limited. Density functional theory (DFT) is employed to investigate the mechanism of methanol dehydrogenation on Ru x P y surfaces. In this work, the P element is introduced into the Ru-based catalyst to obtain dispersed Ru sites and Ru x P y ( x / y = 2 : 1, 1 : 1, and 1 : 2) catalysts are designed. CH 3 OH adsorption, electronic structure of the catalyst, energy barriers for carbon accumulation reactions, and the mechanism of methanol decomposition are systematically calculated. The results of the effective reaction barrier ( E effa) reveal that the order of the activity of the MD reaction is RuP(112) > Ru(0001) > Ru 2 P(210) > RuP 2 (110). The most preferable pathway on RuP(112) is pathway 1 (CH 3 OH* → CH 3 O* → CH 2 O* → CHO* → CO*). After the introduction of P, the weakened CO adsorption enhanced the resistance of catalysts to CO poisoning, and the activation energy of the carbon accumulation reaction increased, indicating that the anti-coking ability of the catalysts is improved. This theoretical study contributes to the design and modulation of highly active and stable metal catalysts for MD reactions.

Background: SARC-F questionnaire is a simple and convenient tool for sarcopenia screening, and SARC-CalF is a modified version of it. The developments of their Chinese versions are warranted for the clinical use for Chinese population. This study aimed to culturally adapt the SARC-F questionnaire into Chinese using standardized methods, validate the reliability and diagnostic accuracy of the Chinese version SARC-F and SARC-CalF against five sarcopenia diagnosis criteria, and determine optimal cut-off values for clinical practice in Chinese population., Methods: The translation and cross-cultural adaptation of SARC-F into Chinese were conducted following the methodological report from European Union Geriatric Medicine Society Sarcopenia Special Interest Group. The Chinese version of SARC-F was validated through a diagnostic test, using diagnostic criteria of sarcopenia recommended by the revised 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) consensus, Asian Working Group for Sarcopenia (AWGS2019) consensus, the International Working Group on Sarcopenia (IWGS), the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium and the Sarcopenia Definition and Outcomes Consortium (SDOC). Additional analysis was done against the criteria of severe sarcopenia according to the revised EWGSOP2 and AWGS2019., Results: The Chinese version of SARC-F was well translated and demonstrated good reliability and acceptability. The diagnostic test included 1859 community-dwelling older individuals from two medical centers. Against five different definitions of sarcopenia, the Chinese version of SARC-F showed reasonable diagnostic accuracy for sarcopenia screening (AUC 0.614-0.821), and was demonstrated low sensitivity (13.7-37.9%) but high specificity (94.8-97.7%) with a cut-off value of ≥ 4. SARC-CalF significantly enhanced the diagnostic accuracy of SARC-F when using definitions of EWGSOP2, AWGS2019 and IWGS (all P ≤ 0.001). A score of ≥ 2 for SARC-F and ≥ 7 for SARC-CalF were established as optimal cut-off points for identifying older individuals as at risk of sarcopenia in Chinese population., Conclusions: The Chinese version SARC-F is of reasonable reliability and validity for sarcopenia screening. Despite its low sensitivity, it proves to be a useful tool to identify severe cases in community taking advantage of its simplicity. SARC-CalF appears to be a more suitable screening tool for clinical use in detecting sarcopenia., (© 2024. The Author(s).)

Sacha Inchi ( Plukenetia volubilis L) (SI) is a traditional natural medicine from tropical rainforests of Amazon region in South America. As a raw material for edible oil, it has various pharmacological effects such as antioxidant, anti-inflammatory, hypolipidemia, and blood pressure lowering, which have attracted increasing attentions of pharmacists. This has prompted researchers to explore its pharmacological effects for potential applications in certain diseases. Among these, the study of its anti-inflammatory effects has become a particularly interesting topic, especially in rheumatoid arthritis (RA). RA is a systemic autoimmune disease, and often accompanied by chronic inflammatory reactions. Despite significant progress in its treatment, there is still an urgent need to find effective anti-RA drugs in regard to safety. This review summarizes the potential therapeutic effects of SI on RA by modulating gut microbiota, targeting inflammatory cells and pathways, and mimicking biologic antibody drugs, predicting the application prospects of SI in RA, and providing references for research aimed at using SI to treat RA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Xiang, Liu, Jiang, Guo, Jin, Sun, Zhang, Wang and Liu.)

This Letter reports the first measurement of the oscillation amplitude and frequency of reactor antineutrinos at Daya Bay via neutron capture on hydrogen using 1958 days of data. With over 3.6 million signal candidates, an optimized candidate selection, improved treatment of backgrounds and efficiencies, refined energy calibration, and an energy response model for the capture-on-hydrogen sensitive region, the relative ν[over ¯]_{e} rates and energy spectra variation among the near and far detectors gives sin^{2}2θ_{13}=0.0759_{-0.0049}^{+0.0050} and Δm_{32}^{2}=(2.72_{-0.15}^{+0.14})×10^{-3}  eV^{2} assuming the normal neutrino mass ordering, and Δm_{32}^{2}=(-2.83_{-0.14}^{+0.15})×10^{-3}  eV^{2} for the inverted neutrino mass ordering. This estimate of sin^{2}2θ_{13} is consistent with and essentially independent from the one obtained using the capture-on-gadolinium sample at Daya Bay. The combination of these two results yields sin^{2}2θ_{13}=0.0833±0.0022, which represents an 8% relative improvement in precision regarding the Daya Bay full 3158-day capture-on-gadolinium result.

Purpose: To investigate the effectiveness of an integrated narrative program (INP) in enhancing the resilience, self-efficacy and quality of life of postoperative NSCLC patients., Methods: 135 patients participated in this trial. 45 participants were recruited into the integrated narrative program group and received both the digital storytelling intervention and narrative therapy after a randomized controlled trial, while the control group (n = 45) received routine care and the intervention group (n = 45) underwent the digital storytelling intervention (DST). Questionnaires were administered to assess resilience, self-efficacy and quality of life at baseline (T0) (within 3 days before surgery), immediately after intervention (T1), one month post-intervention (T2), and three months post-intervention (T3). A linear mixed effects model was conducted via the intention-to-treat analysis., Results: During follow-up assessments, the INP group exhibited significantly greater increase in resilience, self-efficacy, and quality of life (all P < 0.001) compared to both DST group and control group, which were consistent with the sensitivity analysis results (all P < 0.001)., Conclusion: The INP was more effective than DST in improving the resilience, self-efficacy, and quality of life of postoperative NSCLC patients, and these benefits could persist for at least three months post-intervention. Due to the fact that the INP process is relatively complicated, so we recommend the use of web-based platforms for INP interventions in future clinical work., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Acetaminophen (APAP) overdose-induced acute liver injury (ALI) is characterized by extensive oxidative stress, and the clinical interventions for this adverse effect remain limited. Astilbin is an active compound found in the rhizome of Smilax glabra Roxb. with anti-inflammatory and antioxidant activities. Due to its low oral bioavailability, astilbin can accumulate in the intestine, which provides a basis for the interaction between astilbin and gut microbiota (GM). In the present study we investigated the protective effects of astilbin against APAP-induced ALI by focusing on the interaction between astilbin and GM. Mice were treated with astilbin (50 mg·kg -1 ·d -1 , i.g.) for 7 days. After the last administration of astilbin for 2 h, the mice received APAP (300 mg/kg, i.g.) to induce ALI. We showed that oral administration of astilbin significantly alleviated APAP-induced ALI by altering the composition of GM and enriching beneficial metabolites including hydroxytyrosol (HT). GM depletion using an "antibiotics cocktail" or paraoral administration of astilbin abolished the hepatoprotective effects of astilbin. On the other hand, administration of HT (10 mg/kg, i.g.) caused similar protective effects in APAP-induced ALI mice. Transcriptomic analysis of the liver tissue revealed that HT inhibited reactive oxygen species and inflammation-related signaling in APAP-induced ALI; HT promoted activation of the Nrf2 signaling pathway to combat oxidative stress following APAP challenge in a sirtuin-6-dependent manner. These results highlight that oral astilbin ameliorates APAP-induced ALI by manipulating the GM and metabolites towards a more favorable profile, and provide an alternative therapeutic strategy for alleviating APAP-induced ALI., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: Bone morphogenetic protein (BMP) signaling cascade is a phylogenetically conserved stem cell regulator that is aberrantly expressed in non-small cell lung cancer (NSLC) and leukemias. BMP signaling negatively regulates mitochondrial bioenergetics in lung cancer cells. The impact of inhibiting BMP signaling on mitochondrial bioenergetics and the effect this has on the survival of NSLC and leukemia cells are not known., Methods: Utilizing the BMP type 2 receptor (BMPR2) JL189, BMPR2 knockout (KO) in cancer cells, and BMP loss of function mutants in C elegans , we determined the effects of BMPR2 inhibition (BMPR2i) on TCA cycle metabolic intermediates, mitochondrial respiration, and the regulation of mitochondrial superoxide anion (SOA) and Ca ++ levels. We also examined whether BMPR2i altered the threshold cancer therapeutics induce cell death in NSLC and leukemia cell lines. KO of the mitochondria uniporter (MCU) was used to determine the mechanism BMPR2i regulates the uptake of Ca ++ into the mitochondria, mitochondrial bioenergetics, and cell death., Results: BMPR2i increases mtCa ++ levels and enhances mitochondrial bioenergetics in both NSLC and leukemia cell lines that is conserved in C elegans. BMPR2i induced increase in mtCa ++ levels is regulated through the MCU, effecting mitochondria mass and cell survival. BMPR2i synergistically induced cell death when combined with BCL-2 inhibitors or microtubule targeting agents in both NSLC and leukemia cells. Cell death is caused by synergistic increase in mitochondrial ROS and Ca ++ levels. BMPR2i enhances Ca ++ uptake into the mitochondria induced by reactive oxygen species (ROS) produced by cancer therapeutics. Both acute myeloid leukemia (AML) and T-cell lymphoblastic leukemia cells lines were more responsive to the JL189 alone and when combined with venetoclax or navitoclax compared to NSLC., Competing Interests: Competing interests A provisionary patent application has been submitted for the development of BMPR2 inhibitors. There is no active or pending financial agreement regarding these compounds.

The commercialized genetically modified (GM) papaya cultivars have protected papaya from the devastating disease caused by papaya ringspot virus (PRSV). However, papaya leaf distortion mosaic virus (PLDMV), which causes similar infection symptoms but is serologically distinct from PRSV, was found as a competitive threat to the papaya industry. Our study surveyed the occurrence of PRSV and PLDMV as well as the transgenic markers of the 35S promoter from cauliflower mosaic virus (CaMV 35S) and the neomycin phosphotransferase II (NPT II) gene in feral papaya plants, which were found frequently growing outside of cultivated papaya fields on Hainan Island. In total, 123 feral papayas, comprising 62 (50.4%) GM plants and 61 (49.6%) non-GM ones, were sampled. Among them, 23 (18.7%) were positive for PRSV, 49 (39.8%) were positive for PLDMV, including 5 plants co-infected by PRSV and PLDMV, and 56 (45.5%) plants were free of either virus. In traditional papaya growing regions, we detected fewer PRSV-infected plants (2 in 33, 6%) than in other regions (21 in 90, 23%). But overall, whether transgenic or not made no significance in PRSV incidence ( P =0.230), with 9 PRSV-infected plants among 62 GM papayas and 14 among 61 non-GM papayas. Phylogenetic and genetic differentiation analysis showed a clear correlation between PRSV and PLDMV populations and their geographical origins. Negative selection was estimated for the selected gene regions of both viruses. Notably, PLDMV has deviated from neutral evolution and experienced population expansion, exhibiting increased genetic diversity and is becoming the predominant threat to papaya in Hainan.

Objective: To summarize the clinical features and postoperative efficacy of patients with oval window atresia accompanied by facial nerve aberration. Methods: The clinical data of patients with congenital middle ear malformation with facial nerve aberration admitted to our hospital from January 2015 to March 2023 were retrospectively analyzed. There were 97 cases (133 ears) in total. Among them, 39 patients (44 ears) had complete follow-up data, including 27 male patients and 12 females, aged 7-48 years old, with an average age of 17.8 years old. Of these, 14 cases (16 ears) were patients combined with facial nerve aberration, and 25 cases (28 ears) were without facial nerve aberration. The results of imaging examination, pure-tone audiometry, selection of surgical strategy, intraoperative findings and postoperative hearing improvement were summarized and analyzed. The malformations of malleus, incus, stapes, oval window and facial nerve were recorded. Prism 9 software was used to statistically analyze the mean bone conductance and air-bone gap of patients before and after surgery. Results: All the 14 patients (16 ears) with middle ear malformation accompanied by facial nerve aberration and oval window atresia showed poor hearing and no facial palsy since childhood. High resolution CT (HRCT) examination of temporal bone, pure tone audiometry and Gelle test were performed before surgery. The malformations of malleus, incus, stapes, oval window and facial nerve were recorded. Preoperative high-resolution CT (HRCT) examination of temporal bone found 12 ears with 4 or more deformities, accounting for 75.00%, in the group of patients with facial nerve malformation. The preoperative average bone conductive threshold was (15.3±10.4) dB and the average air-bone gap was (46.3±10.6) dB in pure-tone audiometry (0.5, 1, 2, 4kHz). According to the different degrees of facial nerve and ossicle malformation, we performed three different hearing reconstruction strategies for the 14 patients (16 ears) with facial nerve aberration and oval window atresia, including 7 ears of incus bypass artificial stape implantation, 7 ears of Malleostapedotomy (MS) and 2 ears of Malleus-cochlear-prothesis (MCP). After 3 months to 18 months of follow-up, all patients showed no facial paralysis. The postoperative mean bone conductive threshold was (15.7±7.9) dB and air-bone gap was (19.8±8.5) dB. There were significant differences in mean air-bone gap before and after operation ( t =7.766, P <0.05), and there was no significant difference between the mean bone conductive threshold before and after surgery ( t =0.225, P =0.824). There was no significant difference of mean reduction of air-bone gap between patients with and without facial nerve aberration ( t =1.412, P =0.165). There was no significant difference between the three hearing reconstruction strategies. There was no significant displacement of the Piston examined by U-HRCT. Conclusion: For patients of middle ear malformation whose facial nerve cover the oval window partially, incus bypass artificial stape implantation or Malleostapedotomy (MS) can be selected according to the specific condition of auditory ossis malformation, and for patients whose facial nerve completely covers the oval window area, Malleus-cochlear-prothesis (MCP) can be selected. Three types of stapes surgery are safe and reliable for patients with oval window atresia accompanied by facial nerve aberration. There was no significant difference in efficacy between them. Preoperative HRCT assessment of middle ear malformation is effective. There is no significant difference of surgical effect with or without facial nerve aberration. The U-HRCT can be used to evaluate the middle ear malformation before surgery and the Piston implantation status after surgery. Due to the risks of surgery, those who do not want to undergo surgery can choose artificial hearing AIDS, such as hearing aid, vibrating soundbridge, bone bridge or bone-anchored hearing aid.

Viruses are dependent on the host factors for their replication and survival. Therefore, identification of host factors that druggable for antiviral development is crucial. The actin cytoskeleton plays an important role in the virus infection. The dynamics change of actin and its function are regulated by multiple actin-associated proteins (AAPs). However, the role and mechanism of various AAPs in the life cycle of virus are still enigmatic. In this study, we analyzed the roles of actin and AAPs in the replication of pseudorabies virus (PRV). Using a library of compounds targeting AAPs, our data found that multiple AAPs, such as Rho-GTPases, Rock, Myosin and Formin were involved in PRV infection. Besides, our result demonstrated that the actin-binding protein Drebrin was also participated in PRV infection. Further studies are necessary to elucidate the molecular mechanism of AAPs in the virus life cycle, in the hope of mining host factors for antiviral developments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Previous studies revealed that vitamin K might help maintain muscle homeostasis, but this association has received little attention. We aimed to explore the associations of vitamin K intake with skeletal muscle mass and strength., Methods: We included cross-sectional data from the U.S. National Health and Nutrition Examination Survey (NHANES, 2011-2018). Vitamin K intake was assessed via 24-h recall. Covariate-adjusted multiple linear regression and restricted cubic splines were used to evaluate the associations of dietary vitamin K intake with skeletal muscle mass and strength, measured by dual-energy X-ray absorptiometry and handgrip dynamometer, respectively., Results: Dietary vitamin K intake was positively associated with skeletal muscle mass in males (β = 0.05747, p  = 0.0204) but not in females. We also revealed a positive association between dietary vitamin K intake and handgrip strength within the range of 0-59.871 μg/d ( P nonlinear  = 0.049). However, beyond this threshold, increasing vitamin K intake did not cause additional handgrip strength improvements., Conclusion: We provided evidence for a positive relationship between dietary vitamin K intake and skeletal muscle mass in males. Moreover, our study revealed a nonlinear relationship between dietary vitamin K intake and handgrip strength, highlighting an optimal intake range., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Chen, Guo, Wang, Bao, Zhang and Yu.)

A cascade reaction of cyclopropyl alcohols, DABSO (1,4-diazoniabicyclo[2.2.2]octane-1,4-disulfinate), and N -(sulfonyl)acrylamides has been developed. This tandem process went through a cyclopropanol ring opening and Michael addition sequence. The γ-keto sulfinate generated from the reaction between cyclopropanol and DABSO serves as the nucleophilic reagent, and N -(sulfonyl)acrylamide is used as the Michael addition acceptor. By utilizing this strategy, multitudinous sulfone-bridged 1,7-dicarbonyl compounds that contain both a β-sulfonyl amide unit and γ-keto sulfone skeleton were conveniently synthesized.

Elevated serum corin concentrations in patients with cardiac diseases have been associated with adverse cardiovascular events and progressive renal dysfunction. This study aimed to determine the role of serum corin levels in predicting the incidence of acute kidney injury (AKI) and mortality in critically ill patients admitted to intensive care units (ICUs). We screened 323 patients admitted to the ICU in our institution from May 2018 through December 2019. After excluding patients receiving renal replacement therapy, 288 subjects were enrolled. Cases were divided equally into high (n = 144) and low (n = 144) corin groups according to median serum corin levels, using 910 pg/mL as the cut-off point. Patient characteristics and comorbidities were collected from medical records. The primary outcome was AKI within 48 h after ICU admission, while the secondary outcome was all-cause of mortality within 1 year. Compared with the low corin group, patients in the high corin group had higher prevalence rates of diabetes, cirrhosis, and nephrotoxic agent exposure; higher Sequential Organ Failure Assessment scores, white blood cell counts, proteinuria, and serum N-terminal pro-brain natriuretic peptide levels; but had lower initial estimated glomerular filtration rates. Furthermore, elevated serum corin was associated with higher risks of AKI within 48h of ICU admission (43.1% vs. 18.1%, p < 0.001) and all-cause mortality within one year (63.9% vs. 50.0%, p = 0.024). High corin level showed strongly positive results as an independent predictor of AKI (OR 2.15, 95% CI 1.11-4.19, p = 0.024) but not for the all-cause mortality after adjusting for confounding factors in multivariate analyses. Elevated circulating corin predicted AKI in critically ill patients, but did not predict all-cause mortality within 1 year. As a key enzyme in renin-angiotensin-aldosterone system, corin expression may be regulated through a feedback loop following natriuretic peptide resistance and desensitization of natriuretic peptide receptors in different critically ill status., (© 2024. The Author(s).)

Calcination of MgCO 3 is an important industrial reaction, but it causes significant and unfavorable CO 2 production. Calcination in a reducing green hydrogen atmosphere can substantially reduce CO 2 release and produce high value-added products such as CO or hydrocarbons, but the mechanism is still unclear. Here, the in situ transformation process of MgCO 3 interacting with hydrogen and the specific formation mechanism of the high value-added products are thoroughly investigated based on reaction thermodynamic, ab initio molecular dynamics (AIMD) simulations, and density functional theory (DFT) calculations. The reaction thermodynamic parameters of MgCO 3 coupled with hydrogen to produce CO or methane are calculated, revealing that increasing and decreasing the thermal reductive decomposition temperature favors the production of CO and methane, respectively. Kinetically, the energy barriers of each possible production pathway for the dominant products CO and methane are further calculated in conjunction with the AIMD simulation results of the transformation process. The results suggest that CO is produced via the MgO catalytic-carboxyl pathway (CO 2 *→ COOH* trans → COOH* cis → CO*→ CO), which is autocatalyzed by MgO derived from the thermal reductive decomposition of MgCO 3 . For the mechanism of methane formation, it prefers to be produced by the stepwise interaction of carbonates in the MgCO 3 laminates with hydrogen adsorbed on their surfaces (direct conversion pathway: sur-O-CO → sur-O-HCO → sur-O-HCOH → sur-O-HC → sur-O-CH 2 → sur-O-CH 3 → sur-O + CH 4 *).

This Letter presents results of a search for the mixing of a sub-eV sterile neutrino with three active neutrinos based on the full data sample of the Daya Bay Reactor Neutrino Experiment, collected during 3158 days of detector operation, which contains 5.55×10^{6} reactor ν[over ¯]&#95;{e} candidates identified as inverse beta-decay interactions followed by neutron capture on gadolinium. The analysis benefits from a doubling of the statistics of our previous result and from improvements of several important systematic uncertainties. No significant oscillation due to mixing of a sub-eV sterile neutrino with active neutrinos was found. Exclusion limits are set by both Feldman-Cousins and CLs methods. Light sterile neutrino mixing with sin^{2}2θ&#95;{14}≳0.01 can be excluded at 95% confidence level in the region of 0.01  eV^{2}≲|Δm&#95;{41}^{2}|≲0.1  eV^{2}. This result represents the world-leading constraints in the region of 2×10^{-4}  eV^{2}≲|Δm&#95;{41}^{2}|≲0.2  eV^{2}.

The increases in plastic production and inadequate plastic waste management have significantly increased the presence of microplastics (MPs) in the environment. MPs refer to plastic fragments and particles with a size smaller than 5 millimeters. Numerous studies have focused on the impacts of MPs on the environment and living organisms, and explored the potential mechanisms. Humans and other organisms can ingest or carry MPs through various pathways, which have a range of adverse effects on metabolism, functionality, and health. Additionally, due to their larger surface area, MPs could adsorb various pollutants, including heavy metals and persistent organic pollutants, severely affecting the health of animals and humans. Based on research on MPs in recent years, we reviewed the sources and distribution of MPs, examined exposure pathways, toxic effects, and toxicological mechanisms on plants, animals, and human bodies, and provided a prospective outlook on future directions for MP research. This review would be a reference for further assessments of the health risks of MPs.

Aim: To explore and analyse the adaptation process of patients and their families at the point of lung cancer diagnosis., Methods: Totally 23 operable lung cancer patients were included in this study. Colaizzi's method of phenomenology was employed for data analysis., Results: This study found two different aspects of family adaptation at the diagnosis of lung cancer. For family resilience, three themes emerged: (1) Positive family belief systems (giving meaning to a cancer diagnosis and maintaining a positive/optimistic attitude), (2) Flexible family organizational patterns (maintaining the stability of family structure and function, adjusting the relationship between patients and family members and receiving external support and help) and (3) Good communication and problem-solving strategies (open communication on an equal basis, positive and open expression of emotions and collaborative problem-solving). For family vulnerability, three themes were as follows: (1) Negative family belief systems (negative attitudes and concealment and self-isolation due to stigma), (2) Rigid family organizational patterns (adaptation lost, conflicts between family support and patients' willingness and pressure upon social support) and (3) Unhealthy communication and problem-solving (poor communication, emotional asymmetry of family members and tendency to solve problems alone)., Conclusion: The study highlights the existence of the family resilience and family vulnerability at the point of lung cancer diagnosis and provides patient's perspective for understanding family resilience in specific cultural contexts., Patient Contribution: The data were collected through face-to-face interviews., Trail Registration Number: ChiCTR2300074801., (© 2024 John Wiley & Sons Ltd.)

Cancer cells depend on nicotinamide adenine dinucleotide phosphate (NADPH) to combat oxidative stress and support reductive biosynthesis. One major NADPH production route is the oxidative pentose phosphate pathway (committed step: glucose-6-phosphate dehydrogenase, G6PD). Alternatives exist and can compensate in some tumors. Here, using genetically-engineered lung cancer mouse models, we show that G6PD ablation significantly suppresses Kras G12D/+ ;Lkb1 -/- (KL) but not Kras G12D/+ ;P53 -/- (KP) lung tumorigenesis. In vivo isotope tracing and metabolomics reveal that G6PD ablation significantly impairs NADPH generation, redox balance, and de novo lipogenesis in KL but not KP lung tumors. Mechanistically, in KL tumors, G6PD ablation activates p53, suppressing tumor growth. As tumors progress, G6PD-deficient KL tumors increase an alternative NADPH source from serine-driven one carbon metabolism, rendering associated tumor-derived cell lines sensitive to serine/glycine depletion. Thus, oncogenic driver mutations determine lung cancer dependence on G6PD, whose targeting is a potential therapeutic strategy for tumors harboring KRAS and LKB1 co-mutations., (© 2024. The Author(s).)

Objectives: Atopic dermatitis (AD) is a chronic and relapsing dermatologic disease that can affect individuals of all ages, including children and adults. The prevalence of AD has increased dramatically over the past few decades. AD may affect children's daily activities, increase their parents' stress, and increase health expenditure. Constipation is a worldwide issue and may affect the gut microbiome. Some research has indicated that constipation might be associated with risk of atopic disease. The primary objective of this retrospective cohort study was to extend and to explore the link between maternal constipation and risk of atopic dermatitis in offspring. Methods: Using the Longitudinal Health Insurance Database, a subset of Taiwan's National Health Insurance Research Database, we identified 138,553 mothers with constipation and 138,553 matched controls between 2005 and 2016. Propensity score analysis was used matching birth year, child's sex, birth weight, gestational weeks, mode of delivery, maternal comorbidities, and antibiotics usage, with a ratio of 1:1. Multiple Cox regression and subgroup analyses were used to estimate the adjusted hazard ratio of child AD. Results: The incidence of childhood AD was 66.17 per 1,000 person-years in constipated mothers. By adjusting child's sex, birth weight, gestational weeks, mode of delivery, maternal comorbidities, and received antibiotics, it was found that in children whose mother had constipation, there was a 1.26-fold risk of AD compared to the children of mothers without constipation (adjusted hazard ratio [aHR]: 1.26; 95% CI, 1.25-1.28). According to subgroup analyses, children in the maternal constipation group had a higher likelihood of AD irrespective of child's sex, birth weight, gestational weeks, mode of delivery, and with or without comorbidities, as well as usage of antibiotics during pregnancy. Compared to the non-constipated mothers, the aHR for the constipated mothers with laxative prescriptions <12 and ≥12 times within one year before the index date were 1.26; 95% CI, 1.24 -1.28 and 1.40; 95% CI, 1.29-1.52, respectively. Conclusion: Maternal constipation was associated with an elevated risk of AD in offspring. Clinicians should be aware of the potential link to atopic dermatitis in the children of constipation in pregnant women and should treat gut patency issues during pregnancy. More study is needed to investigate the mechanisms of maternal constipation and atopic diseases in offspring., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

To explore the mechanism of Liangfang Wenjing Decoction regulating coiled-coil-helix coiled-coil-helix domain containing 4(CHCHD4) in the treatment of hypoxia on endometriosis(EMs) with cold coagulation and blood stasis. The rat model of cold coagulation and blood stasis syndrome was prepared by the ice-water bath method, and then the EMs model was established by autologous intimal transplantation. The rats were randomly divided into model group, low, medium, and high(4.7, 9.4, and 18.8 g·kg~(-1)) dose groups of Liangfang Wenjing Decoction, Shaofu Zhuyu Decoction group, and sham group, with 10 rats in each group. The rats were given intragastric administration for four weeks. During the modeling, the general condition and vaginal smear of rats were observed, and the blood flow of ears and uterus were detected by laser speckle contrast imaging(LSCI) to judge the syndrome of cold coagulation and blood stasis. After the administration, the general condition of the rats was observed, and the area of ectopic lesions was measured by caliper. The localization and expression of CHCHD4 and hypoxia inducible factors-1α(HIF-1α) were detected by immunohistochemistry, and the mRNA and protein expressions of CHCHD4 and HIF-1α were detected by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot. The primary culture of ectopic endometrial stromal cells(ESCs) from EMs patients was performed, and the CHCHD4 overexpression plasmid was constructed and transfected to establish the ESCs model of CHCHD4 overexpression. The cells were divided into the control group, CHCHD4 overexpression group, CHCHD4 overexpression+control serum group, and CHCHD4 overexpression+Liangfang Wenjing Decoction serum group. The protein expression of CHCHD4 and HIF-1α was detected by Western blot, and the glucose consumption and lactic acid level were detected. The cell proliferation was detected by MTT assay. The experiment found that compared with normal rats, the modeling rats showed symptoms of cold coagulation and blood stasis, such as mental malaise, reduced diet and drinking water, disordered estrous cycle, and blocked blood circulation in ears and uterine microvessels. Compared with the sham group, the ectopic lesions in the model group were uplifted, and the mRNA and protein expressions of CHCHD4 and HIF-1α were significantly increased(P&lt;0.05). Compared with the model group, the symptoms of cold coagulation and blood stasis in each treatment group were improved, and the area of ectopic lesions was significantly reduced(P&lt;0.05 or P&lt;0.01). The mRNA and protein expression levels of CHCHD4 and HIF-1α were significantly decreased(P&lt;0.05 or P&lt;0.01). In the cell model, compared with the control group, the expression of CHCHD4, HIF-1α protein, glucose consumption, lactic acid level, and cell proliferation activity in the CHCHD4 overexpression group were significantly increased(P&lt;0.01). Compared with the CHCHD4 overexpression group, there was no significant change in each index in the control serum group, while the protein expression of CHCHD4 and HIF-1α in the Liangfang Wenjing Decoction serum group was decreased significantly(P&lt;0.05 or P&lt;0.01). The glucose consumption, lactic acid level, and cell proliferation activity decreased significantly(P&lt;0.01). It can be seen from the above that the therapeutic effect of Liangfang Wenjing Decoction on EMs with cold coagulation and blood stasis might be related to reducing the expression of CHCHD4 and then improving the hypoxia of ectopic lesions and ectopic ESCs.

Macroautophagy (autophagy hereafter) is an intracellular nutrient scavenging pathway induced by starvation and other stressors whereby cellular components such as organelles are captured in double-membrane vesicles (autophagosomes), whereupon their contents are degraded through fusion with lysosomes. Two main purposes of autophagy are to recycle the intracellular breakdown products to sustain metabolism and survival during starvation and to eliminate damaged or excess cellular components to suppress inflammation and maintain homeostasis. In contrast to most normal cells and tissues in the fed state, tumor cells up-regulate autophagy to promote their growth, survival, and malignancy. This tumor-cell-autonomous autophagy supports elevated metabolic demand and suppresses tumoricidal activation of the innate and adaptive immune responses. Tumor-cell-nonautonomous (e.g., host) autophagy also supports tumor growth by maintaining essential tumor nutrients in the circulation and tumor microenvironment and by suppressing an antitumor immune response. In the setting of cancer therapy, autophagy is a resistance mechanism to chemotherapy, targeted therapy, and immunotherapy. Thus, tumor and host autophagy are protumorigenic and autophagy inhibition is being examined as a novel therapeutic approach to treat cancer., (Copyright © 2024 Cold Spring Harbor Laboratory Press; all rights reserved.)

Background: The recurrence rate of liver cancer after surgery is high. Radiofrequency ablation (RFA) combined with transcatheter arterial chemoembolization (TACE) is an effective treatment for liver cancer; however, its efficacy in recurrent liver cancer remains unclear., Aim: To investigate the clinical effect of TACE combined with RFA in the treatment of recurrent liver cancer., Methods: Ninety patients with recurrent liver cancer were divided into 2 groups according to treatment plan: Control (RFA alone); and experimental [TACE combined with RFA (TACE + RFA)]. The incidence of increased alanine aminotransferase levels, complications, and other indices were compared between the two groups before and after the procedures., Results: One month after the procedures, the short-term efficacy rate and Karnofsky Performance Status scores of the experimental group were significantly higher than those of the control group ( P < 0.05). Alpha-fetoprotein (AFP) and total bilirubin levels were lower than those in the control group ( P < 0.05); The overall response rate was 82.22% and 66.67% in the experimental and control groups, respectively; The disease control rate was 93.33% and 82.22% in the experimental and control groups, respectively, the differences are statistically significant ( P < 0.05). And there were no statistical differences in complications between the two groups ( P > 0.05)., Conclusion: TACE + RFA was effective for the treatment of recurrent liver cancer and significantly reduced AFP levels and improved various indices of liver function., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: The aim of the study was to explore the factors influencing the availability of medications for children, and establish a machine learning model to provide an empirical basis for the subsequent formulation and improvement of relevant policies., Methods: Design: Cross-sectional survey. Setting: 12 provinces, China. Medical doctors from 25 public hospitals were enrolled. All data were randomly divided into a training set and a validation set at a ratio of 7:3. Three prediction models, namely random forest (RF), logistic regression (LR), and extreme gradient boosting (XGBoost), were developed and compared. The receiver operating characteristic curve (ROC) and the associated area under the curve (AUC) were used to evaluate the three models. A nomogram and clinical impact curve (CIC) for availability of medication were developed., Results: Fifteen of 29 factors in the database that were most likely to be selected were considered to establish the prediction model. The XGBoost model (AUC = 0.915) demonstrated better performance than the RF model (AUC = 0.902) and the LR model (AUC = 0.890). According to the Shapley additive explanation values, the five factors that most significantly affected the availability of medications for children in the XGboost model were as follows: the relatively small number of specialized dosage forms for children; unaffordable medications for children; public education on the accessibility and safety of medication for children; uneven distribution of medical resources, leading to insufficient access to medication for children; and years of service as a doctor. The CIC was used to assess the practical applicability of the factor prediction nomogram., Conclusions: The XGBoost model can be used to establish a prediction model to screen the factors associated with the availability of medications for children. The most important contributing factors to the models were the following: the relatively small number of specialized dosage forms for children; unaffordable medications for children; public education on the accessibility and safety of medication for children; uneven distribution of medical resources, leading to insufficient access to medication for children; and years of service as a doctor., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Guo.)

Background: Organophosphate esters (OPEs) are used extensively as flame retardants and plasticizers. Laboratory studies have shown that OPEs exhibit osteotoxicity by inhibiting osteoblast differentiation; however, little is known about how OPEs exposure is associated with bone health in humans., Objectives: We conducted a cross-sectional study to investigate the association between OPEs exposure and bone mineral density (BMD) in adults in the United States using data from the 2011-2018 National Health and Nutrition Examination Survey (NHANES)., Methods: Multivariate linear regression models were used to assess the association between concentrations of individual OPE metabolites and BMDs. We also used the Bayesian kernel machine regression (BKMR) and quantile g-computation (qgcomp) models to estimate joint associations between OPE mixture exposure and BMDs. All the analyses were stratified according to gender., Results: A total of 3546 participants (median age, 40 years [IQR, 30-50 years]; 50.11% male) were included in this study. Five urinary OPE metabolites with a detection rate of > 50% were analyzed. After adjusting for the potential confounders, OPE metabolite concentrations were associated with decreased total-body BMD and lumbar spine BMD in males, although some associations only reached significance for bis(1-chloro-2-propyl) phosphate (BCPP), dibutyl phosphate (DBUP), and bis(2-chloroethyl) phosphate (BCEP) (β = -0.013, 95% CI: -0.026, -0.001 for BCPP and total-body BMD; β = -0.022, 95% CI: -0.043, -0.0001 for DBUP and lumbar spine BMD; β=-0.018, 95% CI: -0.034, -0.002 for BCEP and lumbar spine BMD). OPE mixture exposure was also inversely associated with BMD in males, as demonstrated in the BMKR and qgcomp models., Conclusions: This study provides preliminary evidence that urinary OPE metabolite concentrations are inversely associated with BMD. The results also suggested that males were more vulnerable than females. However, further studies are required to confirm these findings., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Mitochondrial function is important for both energetic and anabolic metabolism. Pathogenic mitochondrial DNA (mtDNA) mutations directly impact these functions, resulting in the detrimental consequences seen in human mitochondrial diseases. The role of pathogenic mtDNA mutations in human cancers is less clear; while pathogenic mtDNA mutations are observed in some cancer types, they are almost absent in others. We report here that the proofreading mutant DNA polymerase gamma ( PolG D256A ) induced a high mtDNA mutation burden in non-small-cell lung cancer (NSCLC), and promoted the accumulation of defective mitochondria, which is responsible for decreased tumor cell proliferation and viability and increased cancer survival. In NSCLC cells, pathogenic mtDNA mutations increased glycolysis and caused dependence on glucose. The glucose dependency sustained mitochondrial energetics but at the cost of a decreased NAD+/NADH ratio that inhibited de novo serine synthesis. Insufficient serine synthesis, in turn, impaired the downstream synthesis of GSH and nucleotides, leading to impaired tumor growth that increased cancer survival. Unlike tumors with intact mitochondrial function, NSCLC with pathogenic mtDNA mutations were sensitive to dietary serine and glycine deprivation. Thus, mitochondrial function in NSCLC is required specifically to sustain sufficient serine synthesis for nucleotide production and redox homeostasis to support tumor growth, explaining why these cancers preserve functional mtDNA., In Brief: High mtDNA mutation burden in non-small-cell lung cancer (NSCLC) leads to the accumulation of respiration-defective mitochondria and dependency on glucose and glycolytic metabolism. Defective respiratory metabolism causes a massive accumulation of cytosolic nicotinamide adenine dinucleotide + hydrogen (NADH), which impedes serine synthesis and, thereby, glutathione (GSH) and nucleotide synthesis, leading to impaired tumor growth and increased survival., Highlights: Proofreading mutations in Polymerase gamma led to a high burden of mitochondrial DNA mutations, promoting the accumulation of mitochondria with respiratory defects in NSCLC.Defective respiration led to reduced proliferation and viability of NSCLC cells increasing survival to cancer.Defective respiration caused glucose dependency to fuel elevated glycolysis.Altered glucose metabolism is associated with high NADH that limits serine synthesis, leading to impaired GSH and nucleotide production.Mitochondrial respiration defects sensitize NSCLC to dietary serine/glycine starvation, further increasing survival.

Background: Optic nerve sheath diameter (ONSD) is a promising, noninvasive invasive intracranial pressure (ICP) measurement method. This study aims to analyze the differences in ONSD between the left and right eyeballs and the differences in ultrasonic measurement between the transverse and sagittal planes., Methods: Data from a total of 50 eligible patients with various types of brain injury who were admitted to our hospital from May 2019 to June 2021 were analyzed. An ONSD assessment was then performed using Philips B-mode ultrasound, measuring ONSD 3 mm posterior to the eyeballs. The left and right ONSDs in the transverse and sagittal planes were measured. Intraparenchymal fiber optic sensors and catheters were inserted into the ventricles and connected to an external pressure transducer to measure ICP., Results: A total of 164 sonographic measurements of ONSD were performed in 50 patients with brain injury in a prospective observational study. Statistically significant differences were found in ONSD between the transverse and sagittal planes. The difference in the left ONSD between the transverse and sagittal planes was 0.007 ± 0.030 cm ( P = 0.003). The Spearman rank correlation test showed that the correlation coefficient between ICP and left/right ONSD in the transverse/sagittal planes was 0.495 vs 0.546 and 0.559 vs 0.605, respectively. The results showed that the areas under the curve of ONSD in the transverse and sagittal planes were 0.843 and 0.805, respectively. Medcalc software was used to compare the areas under the receiver operator characteristic curve, and the results showed that ONSD in the sagittal plane is generally better than in the transverse plane ( P = 0.0145)., Conclusions: This study found that ONSD in the sagittal plane is superior to the transverse plane regarding the comprehensive efficacy of ICP, and unilateral measurement is sufficient., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by North American Neuro-Ophthalmology Society.)

Objective: To investigate the effect of CD8 + CD28 - T cells on acute graft-versus-host disease(aGVHD) after haploidentical hematopoietic stem cell transplantation(haplo-HSCT)., Methods: The relationship between absolute count of CD8 + CD28 - T cells and aGVHD in 60 patients with malignant hematological diseases was retrospectively analyzed after haplo-HSCT, and the differences in the incidence rate of chronic graft-versus host disease(cGVHD), infection and prognosis between different CD8 + CD28 - T absolute cells count groups were compared., Results: aGVHD occurred in 40 of 60 patients after haplo-HSCT, with an incidence rate of 66.67%. The median occurrence time of aGVHD was 32.5(20-100) days. At 30 days after the transplantation, the absolute count of CD8 + CD28 - T cells of aGVHD group was significantly lower than that of non-aGVHD group ( P =0.03). Thus the absolute count of CD8 + CD28 - T cells at 30 days after transplantation can be used to predict the occurrence of aGVHD to some extent. At 30 days after transplantation, the incidence rate of aGVHD in the low cell count group (CD8 + CD28 - T cells absolute count < 0.06/μl) was significantly higher than that in the high cell count group (CD8 + CD28 - T cells absolute count ≥0.06/μl, P =0.011). Multivariate Cox regression analysis further confirmed that the absolute count of CD8 + CD28 - T cells at 30 days after transplantation was an independent risk factor for aGVHD, and the risk of aGVHD in the low cell count group was 2.222 times higher than that in the high cell count group ( P =0.015). The incidence of cGVHD, fungal infection, EBV infection and CMV infection were not significantly different between the two groups with different CD8 + CD28 - T cells absolute count. The overall survival, non-recurrent mortality and relapse rates were not significantly different between different CD8 + CD28 - T cells absolute count groups., Conclusion: Patients with delayed CD8 + CD28 - T cells reconstitution after haplo-HSCT are more likely to develop aGVHD, and the absolute count of CD8 + CD28 - T cells can be used to predict the incidence of aGVHD to some extent. The absolute count of CD8 + CD28 - T cells after haplo-HSCT was not associated with cGVHD, fungal infection, EBV infection, and CMV infection, and was also not significantly associated with the prognosis after transplantation.

Background and Objectives: Sarcopenia has garnered extensive attention in clinical practice since its high prevalence and significant impact on clinical outcomes. Multiple organizations have published guidance documents on sarcopenia, offering evidence-based recommendations for clinical practice and/or research. We aimed to appraise the methodological quality of the included documents and synthesize available recommendations for the screening, diagnosis, and intervention of sarcopenia., Methods and Study Design: We conducted a search on PubMed, Embase, Scopus, Cochrane Library, China National Knowledge Infrastructure, guideline database, and guideline organizations and professional societies websites for clinical practices, consensus statements and position papers in terms of sarcopenia, muscle atrophy or muscle loss published before April 17, 2023. The AGREE II instrument was used by three independent reviewers to assess the methodological quality of these documents., Results: Thirty-six guidance documents published between 2010 and 2023 were included. Seven documents fulfilled ≥ 50% of all the AGREE II domains. Seven underwent a Delphi process and six graded the strength of the recommendations. The process of screening (n=21), early diagnosis of sarcopenia (n=12), diagnosis of sarcopenia and severe sarcopenia (n=10), and management (n=21) were increasingly recommended. SARC-F (n=14) was the most recommended screening tool, and the assessment of muscle function was considered the first step in diagnosing sarcopenia. The management strategy for both age-related and disease-related sarcopenia mainly focused on exercise and nutrition intervention., Conclusions: The guidance documents have provided referential recommendations that have great guiding significance. But the inconsistency in recommendations and variation in methodological rigour suggests that high-quality evidence is lacking yet., Competing Interests: The authors have no competing interests to declare

Hui Guo,1,2 Tao Wu,2 Qiang Lu,1,3 Miaojing Li,2 Jing-Yue Guo,2 Yuan Shen,4 Zheng Wu,1,3 Ke-Jun Nan,2 Yi Lv,1,3 Xu-Feng Zhang1,3 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China; 2Department of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China; 3Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China; 4Department of Epidemiology and Health Statistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, China Objectives: Surgical resection remains a controversial treatment for hepatocellular carcinoma (HCC) within different Barcelona Clinic Liver Cancer (BCLC) stages. The objective of this study was to evaluate the long-term outcome of patients undergoing surgical resection (SR) compared to non-surgical treatments across different BCLC stages.Patients and methods: One thousand four hundred forty-three HCC patients within BCLC 0, A, B and C stages were identified. Overall survival was compared by log-rank test among patients within different BCLC stages and among patients receiving different treatments (SR vs locoregional therapy [LRT] vs best supportive care). Propensity score matching analysis was introduced to mitigate the confounding biases between the groups.Results: The median survival time of the patients diminished from early, intermediate to advanced BCLC stages (BCLC 0-A 43 [range 0–100] months vs BCLC B 32 [range 0–100] months vs BCLC C 27 [range 0–90] months, all p

MORF4-related gene on chromosome 15 (MRG15), a chromatin remodeller, is evolutionally conserved and ubiquitously expressed in mammalian tissues and cells. MRG15 plays vital regulatory roles in DNA damage repair, cell proliferation and division, cellular senescence and apoptosis by regulating both gene activation and gene repression via associations with specific histone acetyltransferase and histone deacetylase complexes. Recently, MRG15 has also been shown to rhythmically regulate hepatic lipid metabolism and suppress carcinoma progression. The unique N-terminal chromodomain and C-terminal MRG domain in MRG15 synergistically regulate its interaction with different cofactors, affecting its functions in various cell types. Thus, how MRG15 elaborately regulates target gene expression and performs diverse functions in different cellular contexts is worth investigating. In this review, we provide an in-depth discussion of how MRG15 controls multiple physiological and pathological processes., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Atrazine (ATZ) is the most prevalent herbicide that has been widely used in agriculture to control broadleaf weeds and improve crop yield and quality. The heavy use of ATZ has caused serious environmental pollution and toxicity to human health. Lycopene (LYC), is a carotenoid that exhibits numerous health benefits, such as prevention of cardiovascular diseases and nephropathy. However, it remains unclear that whether ATZ causes cardiorenal injury or even cardiorenal syndrome (CRS) and the beneficial role of LYC on it. To test this hypothesis, mice were treated with LYC and/or ATZ for 21 days by oral gavage. This study demonstrated that ATZ exposure caused cardiorenal morphological alterations, and several inflammatory cell infiltrations mediated by activating NF-κB signaling pathways. Interestingly, dysregulation of MAPK signaling pathways and MAPK phosphorylation caused by ATZ have been implicated in cardiorenal diseases. ATZ exposure up-regulated cardiac and renal injury associated biomarkers levels that suggested the occurrence of CRS. However, these all changes were reverted, and the phenomenon of CAR was disappeared by LYC co-treatment. Based on our findings, we postulated a novel mechanism to elucidate pesticide-induced CRS and indicated that LYC can be a preventive and therapeutic agent for treating CRS by targeting MAPK/NF-κB signaling pathways., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Aim: This study aimed to explore the characteristics of stigma in postoperative oral cancer patients to provide a reference for the formulation of targeted intervention measures., Methods: A qualitative study was conducted on 25 postoperative oral cancer patients in a tertiary A hospital in Hunan, China, from March to July 2021. Semi-structured face-to-face interviews focused on experiences of stigma were performed. The interview data was analyzed using the NVivo V.12 software based on the reflexive intuitive thematic analysis method. The paper complies with the COREQ., Results: The stigma experience of postoperative oral cancer patients can be divided into 3 themes: (1) triggers (impaired appearance and oral function and psycho-social pressure); (2) forms (overall isolation, unpleasant feeling of inferiority, and unpleasant social discrimination); (3) coping strategies (positive psychological adjustment, seeking social support and coming out of the unpleasant shadows)., Conclusion: Postoperative oral cancer patients clearly articulated that stigma was present in their lives and they experienced multiple forms of stigma. Further work is needed to increase education and awareness about oral cancer to guide them to take positive coping and reduce stigma., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To verify and compare whether the digital stories could effectively improve the resilience, self-efficacy and quality of life of postoperative NSCLC patients., Materials and Methods: A total of 90 participants at baseline were randomly assigned to two groups, 45 patients per group. The intervention group received the digital storytelling intervention which includes 4 videos on different topics: positive psychological quality, cultivating healthy living habits, establishing good social support, and insisting on scientific exercise, whereas the control group received only routine care. The resilience, self-efficacy, and quality of life were assessed at baseline (T0) (within 3 days before surgery), immediately after intervention (T1), one month after intervention (T2), and three months after intervention (T3). A linear mixed effects model was used to test the effects of the digital storytelling interventions on resilience, self-efficacy, and quality of life., Results: The intervention group reported significantly greater improvements in resilience, self-efficacy, and quality of life (all P < 0.001) at follow-ups than the control group after controlling for age, gender, and education level as covariates. Moreover, the sensitivity analysis results are consistent with the per-protocol, that overall time × group interactions effects were significantly different in resilience, self-efficacy, and quality of life (all P < 0.001)., Conclusion: The digital storytelling intervention based on lung cancer survivors' experience can effectively improve resilience, self-efficacy and quality of life in postoperative lung cancer patients. More comprehensive researches are needed to evaluate the longer-term impacts of the DST and its feasibility for those with more advanced cancer., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In insects, vision is crucial in finding host plants, but its role in nocturnal insects is largely unknown. Vision involves responses to specific spectra of photon wavelengths and opsins plays an important role in this process. Long-wavelength sensitive opsin (LW opsin) and blue-sensitive opsin (BL opsin) are main visual opsin proteins and play important in behavior regulation.We used CRISPR/Cas9 technology to mutate the long-wavelength-sensitive and blue wavelength-sensitive genes and explored the role of vision in the nocturnal invasive pest Tuta absoluta. Light wave experiments revealed that LW2 (-/-) and BL (-/-) mutants showed abnormal wavelength tropism. Both LW2 and BL mutations affected the preference of T. absoluta for the green environment. Mutations in LW2 and BL are necessary to inhibit visual attraction. The elimination of LW2 and BL affected the preference of leaf moths for green plants, and mutations in both induced a preference in moths for white plants. Behavioral changes resulting from LW2 (-/-) and BL (-/-) mutants were not affected by sense of smell, further supporting the regulatory role of vision in insect behavior. To the best of our knowledge, this is the first study to reveal that vision, not smell, plays an important role in the host-seeking behavior of nocturnal insects at night, of which LW2 and BL opsins are key regulatory factors. These study findings will drive the development of the "vision-ecology" theory., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests. This article does not contain any studies with human participants or animals performed by any of the authors., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The current pandemic and future public health emergencies highlight the importance of evaluating a telehealth care model. Previous studies have reached mixed conclusions about the effectiveness of remote monitoring on glycemic control and maternal and infant outcomes in women with gestational diabetes mellitus (GDM)., Objectives: This meta-analysis aimed to evaluate the effectiveness of remote blood glucose monitoring for women with gestational diabetes mellitus and to provide evidence-based guidance on the management of women with gestational diabetes mellitus for policymakers and healthcare providers during situations such as pandemics or natural disasters., Methods: The Cochrane Library, PubMed, Web of Science, EBSCO, Embase, Medline, CINAHL databases, and ClinicalTrials.gov were systematically searched from their inception to July 10, 2021. Randomized controlled trials (RCTs) published in English with respect to remote blood glucose monitoring in women with GDM were included in the meta-analysis. Two independent reviewers performed data extraction and assessed the quality of the studies. Risk ratios, mean differences, 95% confidence intervals, and heterogeneity were calculated., Results: A total of 1265 participants were included in the 11 RCTs. There were no significant differences in glycemic control and maternal-fetal outcomes between the remote monitoring group and a standard care group, which included glycosylated hemoglobin (HbA1c), fasting blood glucose, mean 2-h postprandial blood glucose, caesarean birth, gestational weight gain, shoulder dystocia, neonatal hypoglycemia, and other outcomes., Conclusion: This meta-analysis reveals that it is unclear if remote glucose monitoring is preferable to standard of care glucose monitoring. To improve glycemic control and maternal-fetal outcomes during the current epidemic or other natural disasters, the implementation of double-blind RCTs in the context of simulating similar disasters remains to be studied in the future., (© 2023 Wiley Periodicals LLC.)