Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

Esophageal cancer screening,early detection and treatment:Current insights and future directions

Esophageal cancer ranks among the most prevalent malignant tumors globally,primarily due to its highly aggressive nature and poor survival rates.According to the 2020 global cancer statistics,there were approximately 604000 new cases of esophageal cancer,resulting in 544000 deaths.The 5-year survival rate hovers around a mere 15%-25%.Notably,distinct variations exist in the risk factors associated with the two primary histological types,influencing their worldwide incidence and distribution.Squamous cell carcinoma displays a high incidence in specific regions,such as certain areas in China,where it meets the cost-effect-iveness criteria for widespread endoscopy-based early diagnosis within the local population.Conversely,adenocarcinoma(EAC)represents the most common histological subtype of esophageal cancer in Europe and the United States.The role of early diagnosis in cases of EAC originating from Barrett's esophagus(BE)remains a subject of controversy.The effectiveness of early detection for EAC,particularly those arising from BE,continues to be a debated topic.The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses.In areas with higher incidences,such as China and Japan,early diagnosis is more common,which has led to the advancement of endoscopic methods as definitive treatments.These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality.Early screening,prompt diagnosis,and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.

Tumor necrosis factor-stimulated gene-6 ameliorates early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome-mediated astrocyte pyroptosis

Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.

Development and validation of a prediction model for early screening of people at high risk for colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a serious threat worldwide.Although early screening is suggested to be the most effective method to prevent and control CRC,the current situation of early screening for CRC is still not optimistic.In China,the incidence of CRC in the Yangtze River Delta region is increasing dramatically,but few studies have been conducted.Therefore,it is necessary to develop a simple and efficient early screening model for CRC.AIM To develop and validate an early-screening nomogram model to identify individuals at high risk of CRC.METHODS Data of 64448 participants obtained from Ningbo Hospital,China between 2014 and 2017 were retrospectively analyzed.The cohort comprised 64448 individuals,of which,530 were excluded due to missing or incorrect data.Of 63918,7607(11.9%)individuals were considered to be high risk for CRC,and 56311(88.1%)were not.The participants were randomly allocated to a training set(44743)or validation set(19175).The discriminatory ability,predictive accuracy,and clinical utility of the model were evaluated by constructing and analyzing receiver operating characteristic(ROC)curves and calibration curves and by decision curve analysis.Finally,the model was validated internally using a bootstrap resampling technique.RESULTS Seven variables,including demographic,lifestyle,and family history information,were examined.Multifactorial logistic regression analysis revealed that age[odds ratio(OR):1.03,95%confidence interval(CI):1.02-1.03,P<0.001],body mass index(BMI)(OR:1.07,95%CI:1.06-1.08,P<0.001),waist circumference(WC)(OR:1.03,95%CI:1.02-1.03 P<0.001),lifestyle(OR:0.45,95%CI:0.42-0.48,P<0.001),and family history(OR:4.28,95%CI:4.04-4.54,P<0.001)were the most significant predictors of high-risk CRC.Healthy lifestyle was a protective factor,whereas family history was the most significant risk factor.The area under the curve was 0.734(95%CI:0.723-0.745)for the final validation set ROC curve and 0.735(95%CI:0.728-0.742)for the training set ROC curve.The calibration curve demonstrated a high correlation between the CRC high-risk population predicted by the nomogram model and the actual CRC high-risk population.CONCLUSION The early-screening nomogram model for CRC prediction in high-risk populations developed in this study based on age,BMI,WC,lifestyle,and family history exhibited high accuracy.

Study on the efficacy of early treatment with pirfenidone on the lung function of patients with idiopathic pulmonary fibrosis

BACKGROUND Idiopathic pulmonary fibrosis(IPF)is classified under fibrotic interstitial pneumonia,characterized by a chronic and progressive course.The predominant clinical features of IPF include dyspnea and pulmonary dysfunction.AIM To assess the effects of pirfenidone in the early treatment of IPF on lung function in patients.METHODS A retrospective analysis was performed on 113 patients with IPF who were treated in our hospital from November 2017 to January 2023.These patients were divided into two groups:control group(n=53)and observation group(n=60).In the control group,patients received routine therapy in combination with methylprednisolone tablets,while those in the observation group received routine therapy together with pirfenidone.After applying these distinct treatment approaches to the two groups,we assessed several parameters,including the overall effectiveness of clinical therapy,the occurrence of adverse reactions(e.g.,nausea,vomiting,and anorexia),symptom severity scores,pulmonary function index levels,inflammatory marker levels,and the 6-min walk distance before and after treatment in both groups.RESULTS The observation group exhibited significantly higher rates than the control group after therapy,with a clear distinction(P<0.05).After treatment,the observation group experienced significantly fewer adverse reactions than the control group,with a noticeable difference(P<0.05).When analyzing the symptom severity scores between the two groups of patients after treatment,the observation group had significantly lower scores than the control group,with a distinct difference(P<0.05).When comparing the pulmonary function index levels between the two groups of patients after therapy,the observation group displayed significantly higher levels than the control group,with a noticeable difference(P<0.05).Evaluating the inflammatory marker data(C-reactive protein,interleukin-2[IL-2],and IL-8)between the two groups of patients after therapy,the observation group exhibited significantly lower levels than the control group,with significant disparities(P<0.05).Comparison of the 6-min walking distance data between the two groups of patients after treatment showed that the observation group achieved significantly greater distances than the control group,with a marked difference(P<0.05).CONCLUSION Prompt initiation of pirfenidone treatment in individuals diagnosed with IPF can enhance pulmonary function,elevate inflammatory factor levels,and increase the distance covered in the 6-min walk test.This intervention is conducive to effectively decreasing the occurrence of adverse reactions in patients.

Early Triassic Volcanic Rocks in the Western Yarlung Zangbo Suture Zone:Implications for the Opening of the Neo-Tethys Ocean

In this study,zircon U-Pb dating of volcanic rocks from the Zhongba ophiolite of the Yarlung Zangbo Suture Zone(YZSZ)in southern Xizang(Tibet)yielded an age of 247±3 Ma.According to whole rock geochemical and Sr-NdPb isotopic data,the Early Triassic samples could be divided into two groups:Group 1 with P-MORB affinity,showing initial^(87)Sr/^(86)Sr ratios of 0.70253–0.70602,ε_(Nd)(t)values of 4.2–5.3,(^(206)Pb/^(204)Pb)_(t)ratios of 16.353–18.222,(^(207)Pb/^(204)Pb)_(t)ratios of 15.454–15.564,and(^(208)Pb/^(204)Pb)_(t)ratios of 35.665–38.136;Group 2 with OIB affinity,showing initial^(87)Sr/^(86)Sr ratios of 0.70249–0.70513,ε_(Nd)(t)values of 4.4–4.9,(^(206)Pb/^(204)Pb)_(t)ratios of 17.140–18.328,(^(207)Pb/^(204)Pb)_(t)ratios of 15.491–15.575,and(^(208)Pb/^(204)Pb)_(t)ratios of 36.051–38.247.Group 2 rocks formed by partial melting of the mantle source enriched by a former plume,and assimilated continental crustal material during melt ascension.The formation of Group 1 rocks corresponds to the mixing of OIB melts,with the same components as Group 2 and N-MORBs.The Zhongba Early Triassic rocks belong to the continental margin type ophiolite and formed in the continental–oceanic transition zone during the initial opening of the Neo-Tethys in southern Xizang(Tibet).

The early life immune dynamics and cellular drivers at single-cell resolution in lamb forestomachs and abomasum

Background Four-chambered stomach including the forestomachs(rumen,reticulum,and omasum)and abomasum allows ruminants convert plant fiber into high-quality animal products.The early development of this four-chambered stomach is crucial for the health and well-being of young ruminants,especially the immune development.However,the dynamics of immune development are poorly understood.Results We investigated the early gene expression patterns across the four-chambered stomach in Hu sheep,at 5,10,15,and 25 days of age.We found that forestomachs share similar gene expression patterns,all four stomachs underwent widespread activation of both innate and adaptive immune responses from d 5 to 25,whereas the metabolic function were significantly downregulated with age.We constructed a cell landscape of the four-chambered stomach using single-cell sequencing.Integrating transcriptomic and single-cell transcriptomic analyses revealed that the immune-associated module hub genes were highly expressed in T cells,monocytes and macrophages,as well as the defense-associated module hub genes were highly expressed in endothelial cells in the four-stomach tissues.Moreover,the non-immune cells such as epithelial cells play key roles in immune maturation.Cell communication analysis predicted that in addition to immune cells,non-immune cells recruit immune cells through macrophage migration inhibitory factor signaling in the forestomachs.Conclusions Our results demonstrate that the immune and defense responses of four stomachs are quickly developing with age in lamb's early life.We also identified the gene expression patterns and functional cells associated with immune development.Additionally,we identified some key receptors and signaling involved in immune regulation.These results help to understand the early life immune development at single-cell resolution,which has implications to develop nutritional manipulation and health management strategies based on specific targets including key receptors and signaling pathways.

Efficacy and safety of endoscopic submucosal dissection for early gastric cancer and precancerous lesions in elderly patients

BACKGROUND With advancements in the development of endoscopic technologies,the endo-scopic submucosal dissection(ESD)has been one of the gold-standard therapies for early gastric cancer.AIM To investigate the efficacy and safety ESD in the treatment of early gastric cancer and precancerous lesions in the elderly patients.METHODS Seventy-eight elderly patients with early gastric cancer and precancerous lesions admitted to the Third Affiliated Hospital of Qiqihar Medical University were se-lected and classified into two groups according to the different surgical therapies they received between January 2021 and June 2022.Among them,39 patients treated with ESD were included in an experimental group,and 39 patients treated with endoscopic mucosal resection(EMR)were included in a control group.We compared the basic intraoperative conditions,postoperative short-term recovery,long-term recovery effects and functional status of gastric mucosa between the two groups;the basic intraoperative conditions included lesion resection,intra-operative bleeding and operation time;the postoperative short-term recovery assessment indexes were length of hospital stay and incidence of surgical complic-ations;and the long-term recovery assessment indexes were the recurrence rate at 1 year postoperatively and the survival situation at 1 year and 3 years postoper-atively;and we compared the preoperative and predischarge serum pepsinogen I(PG I)and PG II levels and PG I/PG II ratio in the two groups before surgery and discharge.RESULTS The curative resection rate and the rate of en bloc resection were higher in the experimental group than in the control group.The intraoperative bleeding volume was higher in the experimental group than in the control group.The operation time was longer in the experimental group than that in the control group,and the rate for base residual focus was lower in the experimental group than that of the control group,and the differences were all statistically significant(all P<0.05).The length of hospital stay was longer in the experi-mental group than in the control group,and the incidence of surgical complications,1-year postoperative recu-rrence rate and 3-year postoperative survival rate were lower in the experimental group than in the control group,and the differences were statistically significant(all P<0.05).However,the difference in the 1-year postoperative survival rate was not statistically significant between the two groups(P>0.05).Before discharge,PG I and PG I/PG II ratio were elevated in both groups compared with the preoperative period,and the above indexes were higher in the experimental group than those in the control group,and the differences were statistically significant(both P<0.05).Moreover,before discharge,PG II level was lower in both groups compared with the preoperative period,and the level was lower in the experimental group than in the control group,and the differences were all statistically significant(all P<0.05).CONCLUSION Compared with EMR,ESD surgery is more thorough.It reduces the rate of base residual focus,recurrence rate,surgical complications,and promotes the recovery of gastric cells and glandular function.It is safe and suitable for clinical application.

Early warning method for thermal runaway of lithium-ion batteries under thermal abuse condition based on online electrochemical impedance monitoring

Early warning of thermal runaway(TR)of lithium-ion batteries(LIBs)is a significant challenge in current application scenarios.Timely and effective TR early warning technology is urgently required considering the current fire safety situation of LIBs.In this work,we report an early warning method of TR with online electrochemical impedance spectroscopy(EIS)monitoring,which overcomes the shortcomings of warning methods based on traditional signals such as temperature,gas,and pressure with obvious delay and high cost.With in-situ data acquisition through accelerating rate calorimeter(ARC)-EIS test,the crucial features of TR were extracted using the RReliefF algorithm.TR mechanisms corresponding to the features at specific frequencies were analyzed.Finally,a three-level warning strategy for single battery,series module,and parallel module was formulated,which can successfully send out an early warning signal ahead of the self-heating temperature of battery under thermal abuse condition.The technology can provide a reliable basis for the timely intervention of battery thermal management and fire protection systems and is expected to be applied to electric vehicles and energy storage devices to realize early warning and improve battery safety.

Leveraging machine learning for early recurrence prediction in hepatocellular carcinoma:A step towards precision medicine

The high rate of early recurrence in hepatocellular carcinoma(HCC)post curative surgical intervention poses a substantial clinical hurdle,impacting patient outcomes and complicating postoperative management.The advent of machine learning provides a unique opportunity to harness vast datasets,identifying subtle patterns and factors that elude conventional prognostic methods.Machine learning models,equipped with the ability to analyse intricate relationships within datasets,have shown promise in predicting outcomes in various medical disciplines.In the context of HCC,the application of machine learning to predict early recurrence holds potential for personalized postoperative care strategies.This editorial comments on the study carried out exploring the merits and efficacy of random survival forests(RSF)in identifying significant risk factors for recurrence,stratifying patients at low and high risk of HCC recurrence and comparing this to traditional COX proportional hazard models(CPH).In doing so,the study demonstrated that the RSF models are superior to traditional CPH models in predicting recurrence of HCC and represent a giant leap towards precision medicine.

Validation and performance of three scoring systems for predicting primary non-function and early allograft failure after liver transplantation

Background: Primary non-function(PNF) and early allograft failure(EAF) after liver transplantation(LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function(MEAF), PNF score by King's College(King-PNF) and Balance-and-Risk-Lactate(BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. Methods: A retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic(ROC) and the net reclassification improvement(NRI) and integrated discrimination improvement(IDI) analyses. Results: Of all 720 patients, 28(3.9%) developed PNF and 67(9.3%) developed EAF in 3 months. The overall early allograft dysfunction(EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0(3.5–6.3),-2.1(-2.6 to-1.2), and 5.0(2.0–11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves(AUCs) of 0.872 and 0.891, superior to BAR-Lac(AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. Conclusions: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use of these scores will help early identify PNF, standardize grading of EAF and reasonably select clinical endpoints in relative studies.

Different ENSO Impacts on Eastern China Precipitation Patterns in Early and Late Winter Associated with Seasonally-Varying Kuroshio Anticyclonic Anomalies

Winter precipitation over eastern China displays remarkable interannual variability,which has been suggested to be closely related to El Niño-Southern Oscillation(ENSO).This study finds that ENSO impacts on eastern China precipitation patterns exhibit obvious differences in early(November-December)and late(January-February)winter.In early winter,precipitation anomalies associated with ENSO are characterized by a monopole spatial distribution over eastern China.In contrast,the precipitation anomaly pattern in late winter remarkably changes,manifesting as a dipole spatial distribution.The noteworthy change in precipitation responses from early to late winter can be largely attributed to the seasonally varying Kuroshio anticyclonic anomalies.During the early winter of El Niño years,anticyclonic circulation anomalies appear both over the Philippine Sea and Kuroshio region,enhancing water vapor transport to the entirety of eastern China,thus contributing to more precipitation there.During the late winter of El Niño years,the anticyclone over the Philippine Sea is further strengthened,while the one over the Kuroshio dissipates,which could result in differing water vapor transport between northern and southern parts of eastern China and thus a dipole precipitation distribution.Roughly the opposite anomalies of circulation and precipitation are displayed during La Niña winters.Further analysis suggests that the seasonally-varying Kuroshio anticyclonic anomalies are possibly related to the enhancement of ENSO-related tropical central-eastern Pacific convection from early to late winter.These results have important implications for the seasonal-tointerannual predictability of winter precipitation over eastern China.

Early identification of stroke through deep learning with multi-modal human speech and movement data

Early identification and treatment of stroke can greatly improve patient outcomes and quality of life.Although clinical tests such as the Cincinnati Pre-hospital Stroke Scale(CPSS)and the Face Arm Speech Test(FAST)are commonly used for stroke screening,accurate administration is dependent on specialized training.In this study,we proposed a novel multimodal deep learning approach,based on the FAST,for assessing suspected stroke patients exhibiting symptoms such as limb weakness,facial paresis,and speech disorders in acute settings.We collected a dataset comprising videos and audio recordings of emergency room patients performing designated limb movements,facial expressions,and speech tests based on the FAST.We compared the constructed deep learning model,which was designed to process multi-modal datasets,with six prior models that achieved good action classification performance,including the I3D,SlowFast,X3D,TPN,TimeSformer,and MViT.We found that the findings of our deep learning model had a higher clinical value compared with the other approaches.Moreover,the multi-modal model outperformed its single-module variants,highlighting the benefit of utilizing multiple types of patient data,such as action videos and speech audio.These results indicate that a multi-modal deep learning model combined with the FAST could greatly improve the accuracy and sensitivity of early stroke identification of stroke,thus providing a practical and powerful tool for assessing stroke patients in an emergency clinical setting.

Effect of preload forces on multidimensional signal dynamic behaviours for battery early safety warning

Providing early safety warning for batteries in real-world applications is challenging.In this study,comprehensive thermal abuse experiments are conducted to clarify the multidimensional signal evolution of battery failure under various preload forces.The time-sequence relationship among expansion force,voltage,and temperature during thermal abuse under five categorised stages is revealed.Three characteristic peaks are identified for the expansion force,which correspond to venting,internal short-circuiting,and thermal runaway.In particular,an abnormal expansion force signal can be detected at temperatures as low as 42.4°C,followed by battery thermal runaway in approximately 6.5 min.Moreover,reducing the preload force can improve the effectiveness of the early-warning method via the expansion force.Specifically,reducing the preload force from 6000 to 1000 N prolongs the warning time(i.e.,227 to 398 s)before thermal runaway is triggered.Based on the results,a notable expansion force early-warning method is proposed that can successfully enable early safety warning approximately 375 s ahead of battery thermal runaway and effectively prevent failure propagation with module validation.This study provides a practical reference for the development of timely and accurate early-warning strategies as well as guidance for the design of safer battery systems.

Sedimentary Environment and Mineralization of the Black Shale Polymetallic Layer in the Early Cambrian,SW China:Constraints from in situ LA-ICP-MS Analysis of Pyrite

A polymetallic layer is usually developed at the bottom of the early Cambrian black shale in Guizhou Province.The mineral that makes up the polymetallic layer is related to the sedimentary facies.To analyze the differentiation mechanism between polymetallic deposits(Ni-Mo and V),the Zhijin Gezhongwu profile located in the outer shelf and the Sansui Haishan V deposit located in the lower slope are selected to study the in situ sulfur isotopes and trace elements of pyrite.The results show that δ^(34)S values of pyrite vary widely from−7.8‰to 28‰in the Gezhongwu profile,while the δ^(34)S values are relatively uniform(from 27.8‰to 38.4‰)in the Haishan profile.The isotopic S composition is consistent with the transition that occurs in the sedimentary phase from the shelf to the deep sea on the transgressive Yangtze platform;this indicates that the δ^(34)SO_(4)^(2−)values in seawater must be differently distributed in depositional environments.The sulfur in the Ni-Mo layer is produced after the mixing of seawater and hydrothermal fluid,while the V layer mainly originates from seawater.Overall,the Ni-Mo and V deposits have been differentiated primarily on the basis of the combined effect of continental weathering and hydrothermal fluid.

Arlenea delicata gen.et sp.nov.,a new ephedroid plant from the Early Cretaceous Crato Formation,Araripe Basin,Northeast Brazil

Ephedroid macrofossils have been widely documented in Cretaceous deposits,including numerous from the Lower Cretaceous Yixian Formation of NE China.However,few ephedroid macrofossils have been reported from South America.Herein,we describe a new plant of the family Ephedraceae,Arlenea delicata gen.et sp.nov.,from the Lower Cretaceous Crato Formation of the Araripe Basin,Northeast Brazil,based on the vegetative and reproductive structures.It has the typical morphological characteristics of ephedroid plants,including fertile reproductive branches,opposite phyllotaxy,terminal female cones,a sympodial branching system,longitudinally striated internodes,and swollen nodes.Our new finding is unusual in having inner chlamydosperms subtended by two pairs of bracts,reproductive units connected to branches through swollen receptacles and a smooth seed surface.This new ephedroid taxon from the Crato Formation increases our understanding of plant diversity of this group during the Early Cretaceous.Furthermore,the general morphology(fleshy bracts and enlarged receptacles)of this new fossil discovery indicates that seeds of this plant may have been dispersed by animals such as pterosaurs(mainly the Tapejaridae)and birds(Enantiornithes and Ornituromorpha).If true,this would explain the cosmopolitan distribution of Ephedraceae in the Lower Cretaceous.

Provenance of Conglomerate and Sandstone from Early Permian Shoushangou Formation in Xi Ujimqin,Inner Mongolia:Implications for Understanding Paleo-Asian Ocean Subduction

During the Late Carboniferous to Early Permian,a rift was formed by post-collisional extension after ocean closure or an island arc-related basin formed by Paleo-Asian Ocean(PAO)subduction in the Xi Ujimqin area.Nevertheless,the closure time of the PAO is still under debate.Thus,to identify the origin of the PAO,the geochemistry and U-Pb age of zircons were analyzed for the extra-large deep marine,polymict clastic boulders and sandstones in the Shoushangou Formation within the basin.The analyses revealed magmatic activity and tectonic evolution.The conglomerates include megaclasts of granite(298.8±9.1 Ma)and granodiorite porphyry(297.1±3.1 Ma),which were deposited by muddy debris flow.Results of this study demonstrated that the boulders of granitoids have the geochemistry of typical I-type granite,characterized by low Zr+Nb+Ce+Y and low Ga/Al values.The granitoid boulders were formed in island arc setting,indicating the presence of arc magmatism in the area that is composed of the Late Carboniferous to Early Permian subduction-related granitoid in southern Xi Ujimqin.Multiple diagrams for determining sedimentary provenance using major and trace elements indicate that Shoushangou sediments originated from continental island arc-related felsic rocks.Detrital zircon U-Pb age cluster of 330–280 Ma was obtained,indicating input from granite,ophiolite,Xilin Gol complex,and Carboniferous sources to the south.The basin was geographically developed behind the arc during the Early Permian period because the outcropped intrusive rocks in the Late Carboniferous to Early Permian form a volcanic arc.The comprehensive analyses of source areas suggest that Shoushangou sediments developed in a backarc basin in response to the northward subduction of the PAO.The backarc basin and intrusive rocks,in addition to previously published Late Carboniferous to Early Permian magmatic rocks of arc unit in Xilin Gol,confirm the presence of an Early Permian trencharc-basin system in the region,represented by the Baolidao arc and Xi Ujimqin backarc basin.This study highlights the importance and potential of combined geochemical and geochronological studies of conglomerates and sandstone for reconstructing the geodynamic setting of a basin.

A strength model for cement-stabilized mud subjected to various curing temperatures and its early-stage quality control

The influence of curing temperature on the strength development of cement-stabilized mud has been well documented in terms of strength-increase rate and ultimate strength.However,the strength development model is not mature for the extremely early stages.In addition,there is a lack of studies on quality control methods based on early-stage strength development.This paper presents a strength model for cement-stabilized mud to address these gaps,considering various curing temperatures and early-stage behaviors.In this study,a series of laboratory experiments was conducted on two types of muds treated with Portland blast furnace cement and ordinary Portland cement under four different temperatures.The results indicate that elevated temperatures expedite strength development and lead to higher long-term strength.The proposed model,which combines a three-step conversion process and a hyperbolic model at the reference temperature,enables accurate estimate of the strength development for cement-treated mud with any proportions cured under various temperatures.With this model,a practical early quality control method is introduced for applying cement-stabilized mud in field projects.The back-analysis parameters obtained from a 36-h investigation at temperature of 60C demonstrated a sufficient accuracy in predicting strength levels in practical applications.

Silencing of early auxin responsive genes MdGH3-2/12 reduces the resistance to Fusarium solani in apple

Apple replant disease(ARD)has led to severe yield and quality reduction in the apple industry.Fusarium solani(F.solani)has been identified as one of the main microbial pathogens responsible for ARD.Auxin(indole-3-acetic acid,IAA),an endogenous hormone in plants,is involved in almost all plant growth and development processes and plays a role in plant immunity against pathogens.Gretchen Hagen3(GH3)is one of the early/primary auxin response genes.The aim of this study was to evaluate the function of MdGH3-2 and MdGH3-12 in the defense response of F.solani by treating MdGH3-2/12 RNAi plants with F.solani.The results show that under F.solani infection,RNAi of MdGH3-2/12 inhibited plant biomass accumulation and exacerbated root damage.After inoculation with F.solani,MdGH3-2/12 RNAi inhibited the biosynthesis of acid-amido synthetase.This led to the inhibition of free IAA combining with amino acids,resulting in excessive free IAA accumulation.This excessive free IAA altered plant tissue structure,accelerated fungal hyphal invasion,reduced the activity of antioxidant enzymes(SOD,POD and CAT),increased the reactive oxygen species(ROS)level,and reduced total chlorophyll content and photosynthetic ability,while regulating the expression of PR-related genes including PR1,PR4,PR5 and PR8.It also changed the contents of plant hormones and amino acids,and ultimately reduced the resistance to F.solani.In conclusion,these results demonstrate that MdGH3-2 and MdGH3-12 play an important role in apple tolerance to F.solani and ARD.

Improving early diagnosis of multiple endocrine neoplasia type 1 by assessing the gastrointestinal symptoms,hypercalcemia,and elevated serum gastrin

Despite advancements in the field,early diagnosis of multiple endocrine neoplasia type 1(MEN1)remains unachievable.This letter to the editor highlighted the importance of carefully assessing gastrointestinal symptoms,hypercalcemia,and elevated serum gastrin levels,as suggested by Yuan et al in their paper.They focused on a patient with recurrent abdominal pain and diarrhea whose diagnostic path led to establishing a MEN1 diagnosis within a year.This emphasized the need for clinicians to consider MEN1 in patients with similar presentations,particularly when gastrointestinal symptoms persist or recur after discontinuation of proton pump inhibitors,especially knowing that early recognition and intervention are crucial for improving patient outcomes.