Genomic analysis provides insights into the westward expansion of domesticated peaches in China

Peach, an economically important model plant of the Rosaceae family, has been domesticated and cultivated in China for approximately5 000 years. The Hexi Corridor, an important corridor connecting east-central China and the Tarim Basin, is the starting point of the Silk Road that links China and the Eurasian region. As a globally distributed fruit tree, the spread of peach was accomplished through historical trade routes in the Hexi Corridor and the Tarim Basin. However, knowledge of peach genetic diversity in these regions remains limited. In this study,we examined the relationships and the spread history of domesticated peaches through sequencing and genomic analysis of 161 peach accessions collected from Northwest China, including 43 from the Hexi Corridor and 104 from the Tarim Basin. The results indicate that peach landraces in the Hexi Corridor and the Tarim Basin are derivatives of peaches from the east and south of China (ESC). Notably, the genetic diversity of accessions from both the Hexi Corridor and the Tarim Basin was lower than that of ESC accessions. Reduction of diversity (ROD) and linkage disequilibrium (LD) analyses detected a genetic bottleneck in peaches from these regions. Additionally, these peaches have undergone varying degrees of selection from natural environment. Moreover, genes responsive to biotic and abiotic stresses were under selection, which could be the result of the climate change of Northwest China after the Last Glacial Maximum (LGM). Our findings provide a better understanding of the genetic basis of peach migration in Northwest China. Furthermore, this study expands the available genomic data for peaches and provides critical information for future peach breeding programs.

Peculiarity of transcriptional and H3K27me3 dynamics during peach bud dormancy

Bud dormancy facilitates the survival of meristems under harsh environmental conditions.To elucidate how molecular responses to chilling accumulation controlling dormancy in peach buds,chromatin immunoprecipitation sequencing to identify the H3K27me3 modifications and RNA sequencing of two peach cultivars with pronounced differences in chilling requirement were carried out,the results showed that genes associated with abscisic acid and gibberellic acid signal pathways play key roles in dormancy regulation.The results demonstrated that peach flower bud differentiation occurred continuously in both cultivars during chilling accumulation,which was correlated with the transcript abundance of key genes involved in phytohormone metabolism and flower bud development under adverse conditions.The more increased strength in high chillingrequirement cultivar along with the chilling accumulation at the genome-wide level.The function of the dormancy-associated MADS-box gene PpDAM6 was identified,which is involved in leaf bud break in peach and flower development in transgenic Nicotiana tabacum(NC89).In addition,PpDAM6 was positively regulated by PpCBF,and the genes of putative dormancy-related and associated with metabolic pathways were proposed.Taken together,these results constituted a theoretical basis for elucidating the regulation of peach bud dormancy transition.

Research Status of CAR-T Cell Immunotherapy in Tumor Treatment

In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has made breakthroughs in the treatment of hematological tumors. However, due to the different characteristics of solid tumors from hematological tumors, CAR-T has not achieved good efficacy in the treatment of solid tumors. The key factors limiting the efficacy of CAR-T mainly include the solid tumor cells themselves and their special tumor microenvironment (TME), which damage CAR-T function in multiple processes such as CAR-T infiltration to tumor tissue sites, CAR-T maintaining anti-tumor activity in TME, and target recognition and killing of tumor cells by CAR-T. To solve these problems, more and more preclinical studies have proposed potentially effective solutions, and corresponding clinical studies have been carried out one after another. In this article, the existing challenges and corresponding optimization strategies of CAR-T cell therapy for solid tumors will be reviewed, to provide a reference for the future exploration of CAR-T therapy.

蛋白糖基化修饰在肿瘤多药耐药中的作用

恶性肿瘤为目前人类延长预期寿命的最大障碍。化疗是临床上抗肿瘤治疗的重要手段,但恶性肿瘤极易在化疗中产生多药耐药性(multidrug resistance,MDR)从而导致患者的不良预后。恶性肿瘤的MDR已被证实通过多种机制产生,如药物转运与吸收、细胞凋亡和DNA损伤修复等。蛋白糖基化修饰在肿瘤MDR中扮演重要角色。本文通过对蛋白糖基化修饰在肿瘤MDR中的分子机制进行综述,以期为临床上恶性肿瘤MDR的逆转提供理论基础。

Stepwise sedation for elderly patients with mild/moderate COPD during upper gastrointestinal endoscopy

AIM: To investigate stepwise sedation for elderly patients with mild/moderate chronic obstructive pulmonary disease (COPD) during upper gastrointestinal (GI) endoscopy. METHODS: Eighty-six elderly patients with mild/moderate COPD and 82 elderly patients without COPD scheduled for upper GI endoscopy were randomly assigned to receive one of the following two sedation methods: stepwise sedation involving three-stage administration of propofol combined with midazolam [COPD with stepwise sedation (group Cs), and nonCOPD with stepwise sedation (group Ns)] or continuous sedation involving continuous administration of propofol combined with midazolam [COPD with continuous sedation (group Cc), and non-COPD with continuous sedation (group Nc)]. Saturation of peripheral oxygen (SpO 2 ), blood pressure, and pulse rate were monitored, and patient discomfort, adverse events, drugs dosage, and recovery time were recorded. RESULTS: All endoscopies were completed successfully. The occurrences of hypoxemia in groups Cs, Cc, Ns, and Nc were 4 (9.3%), 12 (27.9%), 3 (7.3%), and 5 (12.2%), respectively. The occurrence of hypoxemia in group Cs was significantly lower than that in group Cc (P < 0.05). The average decreases in value of SpO 2 , systolic blood pressure, and diastolic blood pressure in group Cs were significantly lower than those in group Cc. Additionally, propofol dosage and overall rate of adverse events in group Cs were lower than those in group Cc. Finally, the recovery time in group Cs was significantly shorter than that in group Cc, and that in group Ns was significantly shorter than that in group Nc (P < 0.001). CONCLUSION: The stepwise sedation method is effective and safer than the continuous sedation method for elderly patients with mild/moderate COPD during upper GI endoscopy.

Stereolithographic 3D Printing-Based Hierarchically Cellular Lattices for High-Performance Quasi-Solid Supercapacitor

3D printing-based supercapacitors have been extensively explored,yet the rigid rheological requirement for corresponding ink preparation significantly limits the manufacturing of true 3D architecture in achieving superior energy storage.We proposed the stereolithographic technique to fabricate the metallic composite lattices with octet-truss arrangement by using electroless plating and engineering the 3D hierarchically porous graphene onto the scaffolds to build the hierarchically cellular lattices in quasi-solid supercapacitor application.The supercapacitor device that is composed of composite lattices span several pore size orders from nm to mm holds promising behavior on the areal capacitance(57.75 mF cm-2),rate capability(70% retention,2-40 mA cm-2),and long lifespan(96% after 5000 cycles),as well as superior energy density of 0.008 mWh cm-2,which are comparable to the state-of-the-art carbon-based supercapacitor.By synergistically combining this facile stereolithographic 3D printing technology with the hierarchically porous graphene architecture,we provide a novel route of manufacturing energy storage device as well as new insight into building other high-performance functional electronics.

Highly Sensitive Pseudocapacitive Iontronic Pressure Sensor with Broad Sensing Range

Flexible pressure sensors are unprecedentedly studied on monitoring human physical activities and robotics.Simultaneously,improving the response sensitivity and sensing range of flexible pressure sensors is a great challenge,which hinders the devices’practical application.Targeting this obstacle,we developed a Ti_(3)C_(2)T_(x)-derived iontronic pressure sensor(TIPS)by taking the advantages of the high intercalation pseudocapacitance under high pressure and rationally designed structural configuration.TIPS achieved an ultrahigh sen-sitivity(S_(min)>200 kPa^(−1),S_(max)>45,000 kPa^(−1))in a broad sensing range of over 1.4 MPa and low limit of detection of 20 Pa as well as stable long-term working durability for 10,000 cycles.The practical application of TIPS in physical activity monitoring and flexible robot manifested its versatile potential.This study provides a demonstration for exploring pseudocapacitive materials for building flexible iontronic sensors with ultrahigh sensitivity and sensing range to advance the development of high-performance wearable electronics.

Flexible Waterproof Piezoresistive Pressure Sensors with Wide Linear Working Range Based on Conductive Fabrics

Developing flexible sensors with high working performance holds intense interest for diverse applications in leveraging the Internet-of-things(IoT)infrastructures.For flexible piezoresistive sensors,traditionally most efforts are focused on tailoring the sensing materials to enhance the contact resistance variation for improving the sensitivity and working range,and it,however,remains challenging to simultaneously achieve flexible sensor with a linear working range over a high-pressure region(>100 kPa)and keep a reliable sensitivity.Herein,we devised a laserengraved silver-coated fabric as"soft"sensor electrode material to markedly advance the flexible sensor's linear working range to a level of 800 kPa with a high sensitivity of 6.4 kPa^-1 yet a fast response time of only 4 ms as well as long-time durability,which was rarely reported before.The integrated sensor successfully routed the wireless signal of pulse rate to the portable smartphone,further demonstrating its potential as a reliable electronic.Along with the rationally building the electrode instead of merely focusing on sensing materials capable of significantly improving the sensor's performance,we expect that this design concept and sensor system could potentially pave the way for developing more advanced wearable electronics in the future.

Tailoring mechanical properties of PμSL 3D-printed structures via size effect

Projection micro stereolithography(PμSL)has emerged as a powerful three-dimensional(3D)printing technique for manufacturing polymer structures with micron-scale high resolution at high printing speed,which enables the production of customized 3D microlattices with feature sizes down to several microns.However,the mechanical properties of as-printed polymers were not systemically studied at the relevant length scales,especially when the feature sizes step into micron/sub-micron level,limiting its reliable performance prediction in micro/nanolattice and other metamaterial applications.In this work,we demonstrate that PμSL-printed microfibers could become stronger and significantly more ductile with reduced size ranging from 20μm to 60μm,showing an obvious size-dependent mechanical behavior,in which the size decreases to 20μm with a fracture strain up to~100%and fracture strength up to~100 MPa.Such size effect enables the tailoring of the material strength and stiffness of PμSL-printed microlattices over a broad range,allowing to fabricate the microlattice metamaterials with desired/tunable mechanical properties for various structural and functional applications.

Small bowel volvulus with jejunal diverticulum: Primary or secondary?

Small bowel volvulus,which is torsion of the small bowel and its mesentery,is a medical emergency,and is categorized as primary or secondary type. Primary type often occurs without any apparent intrinsic anatomical anomalies,while the secondary type is common clinically and could be caused by numerous factors including postoperative adhesions,intestinal diverticulum,and/or tumors. Here,we report a rare case of a 60-year-old man diagnosed with small bowel volvulus using multidetector computed tomography(MDCT) angiography. Further discovery by laparotomy showed one jejunal diverticulum,longer corresponding mesentery with a narrower insertion,and a lack of mesenteric fat. This case report includes several etiological factors of small bowel volvulus,and we discuss the possible cause of small bowel volvulus in this patient. We also highlight the importance of MDCT angiography in the diagnosis of volvulus and share our experience in treating this disease.

Temporal and spatial evolution of surface sediments characteristics in the Dagu River estuary and their dynamic response mechanism

Based on the 39 surface sediment samples collected in the flood season and the dry season in 2012 respectively and the measured hydrological data in October 2012, the sediment grain size characteristics has been analyzed and the response mechanism of surface sediments to estuarine hydrodynamics was revealed by calculating the range of waves and tidal currents. The results show that:(1) The grain size of the surface sediment samples decreased gradually from land to sea in the flood season. The fine sediment was redistributed under marine hydrodynamics in the dry season and the sediments showed coarser tendency ingeneral;(2) tidal current stirring sediment was very obvious in Dagu River estuary area, and wave stirring sediments mainly occurred in the tidal flat area and estuary sand bar area;(3) in the flood season, surface sediment sat the estuary were transported towards south and southeast. In the dry season, surface sediments were transported towards southwest at the north area of Jiaozhou Bay Bridge, and sediments were transported towards northeast area at the south of Jiaozhou Bay Bridge.

Downregulation of serum mi R-17 and mi R-106b levels in gastric cancer and benign gastric diseases

Altered micro RNA（mi RNA） associated with gastric cancer（GC） development and mi R-17 and mi R-106 b were differentially expressed in GC tissues. This study detected serum levels of mi R-17 and mi R-106 b expression in GC, benign gastric disease（BGD） and healthy controls to assess them as tumor markers for GC. Serum samples from 40 GC, 32 BGD（10 gastric ulcer, 14 gastric polyps, and 8 gastric ulcer with polyps） and 36 healthy individuals were subjected to quantitative reverse transcription polymerase chain reaction（q RT-PCR） analysis of mi R-17 and mi R-106 b expression. The data showed that the serum levels of mi R-17 and mi R-106 b were significantly reduced in healthy individuals and BGD patients compared to GC patients. There was a significant association of mi R-17 and mi R-106 b expression with age, but not with other clinicopathological features, such as gender, tumor differentiation, stage and lymphatic metastasis. Further analysis showed that, in discriminating GC patients from healthy controls, mi R-17 could yield a receiver-operating characteristic（ROC） area under the curve（AUC） of 0.879 with 80.6% sensitivity and 87.5% specificity and mi R-106 b could yield an AUC of 0.856 with 75.0% sensitivity and 92.5% specificity. The combined AUC of mi R-17 and mi R-106 b was 0.913 with 83.3% sensitivity and 87.5% specificity. Collectively, these data suggest that detection of serum mi R-17 and mi R-106 b levels should be further evaluated as novel non-invasive biomarkers in early GC detection and surveillance of disease progression.

Cretaceous terrestrial deposits in China

As an important part of an epidermic system,terrestrial deposits can provide a good record of major geological events in the Cretaceous epidemic system.This article is a review of the geological background,paleogeography,paleoclimate,basin evolution and sedimentary characteristics in China through the Cretaceous period,in order to provide a comprehensive understanding for interested researchers.During the Berriasian-Hauterivian age,red-mainly fluvial and shallow lacustrine deposition developed under arid and semi-arid climates in westen China when eastern China had been occupied by the " East Plateau”.During the Barremian-Albian,age coal-bearing depositions occurred to the north of the Yanshan Mountain under the wet and warm climate.However,mainly red fluvial and shallow lacustrine depositions prevailed in most of the south to the Yanshan Mountain except basins where seawater could enter and caused mostly green depositions.During the Cenomanian-Santonian age,high land uplift took place in northwestern China.Mainly red deposition with developed alluvial plains occupied southwestern China and South China when the Songliao Basin was filled by black deep lacustrine mud shale caused by transgression.Mainly red deposition under an arid and semi-arid climate occupied all basins in China during the Campanian-Maastrichtian age.

Dynamic changes of autophagy during hypertrophic scar formation and the role of autophagy intervention

Background:The role of autophagy in the formation of hypertrophic scars(HS)remains unclear.This study aimed to explore the role and potential mechanism of autophagy during the development of HS.Methods:RNA and protein expression levels of Beclin-1,p62,and LC3II in normal skin tissues and HS specimens from different patients were examined.Autophagy inducers and inhibitors were used to cure established HS in rabbit ears,and the expression of Beclin-1,p62,and LC3II at the RNA and protein level was determined.Lastly,the effects of autophagy inducers and inhibitors on HS development were analyzed.Results:Compared to normal skin tissues,the expression of LC3II and Beclin-1 was higher(P<0.05),while that of p62 was lower(P<0.05)in HS tissues.In addition,the LC3II/LC3I ratio was increased during HS formation,and the altered expression of the three proteins stabilized after one year.Administration of autophagy inducers enhanced the formation of HS as well as the expression levels of LC3II and Beclin-1 but decreased p62 expression.Meanwhile,administration of autophagy inhibitors increased the expression of LC3II,Beclin-1,and p62,along with reduced HS formation.Conclusion:Autophagic activity increased during HS initiation and subsequent stabilization.In addition,autophagy inhibitors were able to inhibit HS formation by suppressing autophagy,whereas autophagy inducers promoted scar hyperplasia by enhancing autophagy。

Effects of grain's shape-and size-polydispersities,orientation,and area fraction on tortuosity and permeability of 2D granular media

The microstructure of granular media, including grain's shape- and size-polydispersities, orientation, and area fraction can potentially affect its permeability. However, few studies consider the coupling effects of these features. This work employs geometrical probability and stereology to establish quantitative relationships between the above microstructural features and the geometric tortuosity of the two-dimensional granular media containing superellipse, superoval, and polygon grains. Then the lattice Boltzmann method (LBM) is used to determine the permeabilities of these granular media. By combining the tortuosity model and the LBM-derived permeabilities, modified K–C equations are formulated to predict the permeability and the shape factor, considering the grain's shape- and size-polydispersities, orientation, and area fraction. The reliability of these methods can be verified by comparing them with both our simulations and available experimental, theoretical, and numerical data reported in the literature. The findings implicate that the tortuosity and permeability of the granular media are strongly correlated with the grain's shape, orientation, and area fraction but unaffected by the size polydispersity and spatial arrangement of grains. Only circularity is not enough to derive a unified formula for considering the impact of grain shape on tortuosity and permeability, other shape parameters need to be explored in the future.

Optimization of ferroelectricity and endurance of hafnium zirconium oxide thin films by controlling element inhomogeneity

Ferroelectric thin films based on HfO_(2) have garnered increasing attention worldwide,primarily due to their remarkable compatibility with silicon and scalability,in contrast to traditional perovskite-structured ferroelectric materials.Nonetheless,significant challenges remain in their widespread commercial utilization,particularly concerning their notable wake-up effect and limited endurance.To address these challenges,we propose a novel strategy involving the inhomogeneous distribution of Hf/Zr elements within thin films and explore its effects on the ferroelectricity and endurance of Hf_(0.5)Zr_(0.5)O_(2) thin films.Through techniques such as grazing incidence X-ray diffraction,transmission electron microscopy,and piezoresponse force microscopy,we investigated the structural characteristics and domain switching behaviors of these materials.The experimental results indicate that the inhomogeneous distribution of Hf/Zr contributes to improving the frequency stability and endurance while maintaining a large remnant polarization in Hf_(0.5)Zr_(0.5)O_(2) ferroelectric thin films.By adjusting the distribution of Zr/Hf within the Hf_(0.5)Zr_(0.5)O_(2) thin films,significant enhancements in the remnant polarization(2P_(r)>35μC/cm2)and endurance(>109)along with a reduced coercive voltage can be achieved.Additionally,the fabricated ferroelectric thin films also exhibit high dielectric tunability(≥26%)under a low operating voltage of 2.5 V,whether in the wake-up state or not.This study offers a promising approach to optimize both the ferroelectricity and endurance of HfO_(2)-based thin films.

Do age-related macular degeneration genes show association with keratoconus?

Background:Keratoconus(KC)is a common corneal condition with an unknown gender predominance.Although numerous studies have investigated the genetic component of KC,no specific genes have yet been attributed to the condition.We recently reported posterior segment changes occurring in the eyes of KC patients.However,it is not clear whether these changes are part of KC pathogenesis or reflect changes in anatomical features of the eye manifested by changes at the cornea.Given retinal changes represent the main characteristics observed in agerelated macular degeneration(AMD)and that pleiotropy has been demonstrated between different eye diseases,we wished to assess if known AMD associated genes were also associated with KC.Methods:A total of 248 KC subjects and 366 non-KC(control)subjects were recruited from public and private clinics in Melbourne for this analysis.Nineteen single nucleotide polymorphisms(SNPs)previously associated with AMD,including rs10490924(ARMS2/HTRA1),rs10737680(CFH),rs13278062(TNFRSF10A),rs1864163(CETP),rs2230199(C3),rs3130783(IER3/DDR1),rs334353(TGFBR1),rs3812111(COL10A1),rs429608(C2/CFB),rs4420638(APOE),rs4698775(CFI),rs5749482(TIMP3),rs6795735(ADAMTS9),rs8017304(RAD51B),rs8135665(SLC16A8),rs920915(LIPC),rs943080(VEGFA),rs9542236(B3GALTL)and rs13081855(COL8A1/FILIP1L),were genotyped in this cohort.Logistic regression was applied to evaluate the association between these SNPs and KC on both genders together,as well as each gender separately.Linear regression was also applied to assess the association between SNPs and corneal curvature.Bonferroni correction was applied to adjust for multiple testing.Results:Genotyping data were available for 18 SNPs.The SNP,rs6795735(ADAMTS9)was significantly associated with KC(p=3.5×10−4)when both genders were assessed,whereas rs5749482(TIMP3)was only associated in males(p=7.7×10−4)following Bonferroni multiple correction.However,when the covariates of age and gender were included,the associations became non-significant.In addition,none of the SNPs appeared significant for corneal curvature.Conclusions:Our study suggested a potential association of rs6795735 in the ADAMTS9 gene and rs5749482 in the TIMP3 gene in KC and that different associations may be gender specific.Overall,SNPs initially identified as associated with AMD following multiple correction may be further impacted by other factors such as age or gender and further studies are needed to resolve this issue.

减重代谢手术预防胃食管反流病的研究进展

胃食管反流病(GERD)是常见的消化道疾病。肥胖是GERD的一个独立危险因素。腹腔镜袖状胃切除术(LSG)在减重代谢手术中越来越普及,并且操作简单、并发症较少,但在治疗肥胖患者术后抗反流疗效方面仍存在争议。有研究报道,LSG可能破坏抗反流屏障功能,如His角功能改变、膈肌连续性的破坏以及术后食管裂孔疝增加。His角是胃食管连接处的重要抗反流屏障之一,重建His角已被证实能有效缓解GERD症状,LSG联合His重建术有望成为有效预防肥胖术后GERD的措施。因此,本文主要就减重手术预防GERD的研究做一综述,旨在探讨肥胖患者术后GERD的有效治疗,以改善患者GERD的症状以及其生活质量,为GERD的外科治疗提供借鉴。

TP53BP2:Roles in suppressing tumorigenesis and therapeutic opportunities

Malignant tumor is still a major problem worldwide.During tumorigenesis or tumor development,tumor suppressor p53-binding protein 2(TP53BP2),also known as apoptosis stimulating protein 2 of p53(ASPP2),plays a critical role in p53 dependent and independent manner.Expression of TP53BP2 is highly correlated with the prognosis and survival rate of malignant tumor patients.TP53BP2 can interact with p53,NF-κB p65,Bcl-2,HCV core protein,PP1,YAP,CagA,RAS,PAR3,and other proteins to regulate cell function.Moreover,TP53BP2 can also regulate the proliferation,apoptosis,autophagy,migration,EMT and drug resistance of tumor cells through downstream signaling pathways,such as NF-κB,RAS/MAPK,mevalonate,TGF-β1,PI3K/AKT,aPKC-ι/GLI1 and autophagy pathways.As a potential therapeutic target,TP53BP2 has been attracted more attention.We review the role of TP53BP2 in tumorigenesis or tumor development and the signal pathway involved in TP53BP2,which may provide more deep insight and strategies for tumor treatment.

The tRNA-derived fragment tRF-5022a positively regulates melanogenesis

The tRNA-derived fragments(tRFs)are small non-coding RNAs containing fewer than 50 nucleotides that are abundant in humans and have various biological functions.However,their roles and mechanisms in melanogenesis are unclear.In this study,we firstly investigated the change in the expres-sion profile of tRFs in melanocytes after UVB irradiation through tsRNA sequencing.UVB-induced melanogenesis led to the upregulation of 119 tRFs and the downregulation of 103 tRFs.