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Object: The benefits of low-dose esketamine for painless gastrointestinal endoscopy remain unclear. As such, the present study aimed to investigate the efficacy and safety of low-dose esketamine for this procedure. Methods: Seven common databases were searched for clinical studies investigating low-dose esketamine for painless gastrointestinal endoscopy. Subsequently, a meta-analysis was performed to synthesize and analyze the data extracted from studies fulfilling the inclusion criteria. Results: Meta-analysis revealed that, compared with propofol, low-dose esketamine in combination with propofol significantly reduced recovery time by 0.56 min (mean difference [MD] −0.56%, 95% confidence interval (CI) −1.08 to −0.05, p = 0.03), induction time by 9.84 s (MD −9.84, 95% CI −12.93 to −6.75, p < 0.00001), propofol dosage by 51.05 mg (MD −51.05, 95% CI −81.53 to −20.57, p = 0.01), and increased mean arterial pressure by 6.23 mmHg (MD 6.23, 95% CI 1.37 to 11.08, p = 0.01). Meanwhile, low-dose esketamine reduced injection pain by 63% (relative risk [RR] 0.37, 95% CI 0.28 to 0.49, p < 0.00001), involuntary movements by 40% (RR 0.60, 95% Cl 0.42 to 0.85, p < 0.005), choking by 42% (RR 0.58, 95% Cl 0.38 to 0.88, p = 0.01), bradycardia by 68% (RR 0.32, 95% Cl 0.18 to 0.58, p = 0.0002), hypotension by 71% (RR 0.29, 95% Cl 0.21 to 0.40, p < 0.00001), respiratory depression by 63% (RR 0.37, 95% 0.26 to 0.51, p < 0.00001), additional cases of propofol by 53% (RR 0.47, 95% Cl 0.29 to 0.77, p = 0.002), and increased hypertension by 1000% (RR 11.00, 95% Cl 1.45 to 83.28, p = 0.02). There were no significant differences in mean heart rate, mean oximetry saturation, delirium, dizziness, vomiting, tachycardia, and hypoxemia. Subgroup analyses revealed that, compared with other dose groups, 0.25 mg/kg esketamine afforded additional benefits in recovery and induction time, mean arterial pressure, involuntary movements, hypoxemia, and respiratory depression. Conclusion: Low-dose esketamine was found to be safe and effective for providing anesthesia during gastrointestinal endoscopy, with 0.25 mg/kg identified as the optimal dose within the dosage ranges examined. However, caution should be exercised when administering this drug to patients with inadequate preoperative blood pressure control.

Homo sapiens was present in northern Asia by around 40,000 years ago, having replaced archaic populations across Eurasia after episodes of earlier population expansions and interbreeding 1 – 4 . Cultural adaptations of the last Neanderthals, the Denisovans and the incoming populations of H. sapiens into Asia remain unknown 1 , 5 – 7 . Here we describe Xiamabei, a well-preserved, approximately 40,000-year-old archaeological site in northern China, which includes the earliest known ochre-processing feature in east Asia, a distinctive miniaturized lithic assemblage with bladelet-like tools bearing traces of hafting, and a bone tool. The cultural assembly of traits at Xiamabei is unique for Eastern Asia and does not correspond with those found at other archaeological site assemblages inhabited by archaic populations or those generally associated with the expansion of H. sapiens , such as the Initial Upper Palaeolithic 8 – 10 . The record of northern Asia supports a process of technological innovations and cultural diversification emerging in a period of hominin hybridization and admixture 2 , 3 , 6 , 11 . A cultural assembly of traits at a 40,000-year-old archaeological site at Xiamabei, China supports a model of repeated early human expansions, cultural exchange and innovation in east Asia.

Climate in Eastern Asia is composed of monsoon climate in the east, arid and semi-arid climate in the north and west, and the cold and dry climate of Qinghai-Tibetan Plateau in the southwest. The underlying causes for the evolution of East Asian cli- mate during late Cenozoic have long been investigated and debated, particularly with regards to the role played by the Qing- hai-Tibetan Plateau uplift and the global cooling. In this paper, we reviewed major research developments in this area, and summarized the important results. Based on a synthesis of data, we propose that the Qinghai-Tibetan Plateau uplift alone can- not fully explain the formation of monsoon and arid climates in Eastern Asia during the past 22-25 Ma. Other factors such as the global ice volume and high-latitude temperature changes have also played a vital role. Moreover, atmospheric CO2 changes may have modulated the monsoon and dry climate changes by affecting the location of the inter-tropical convergence zone （ITCZ）, which controls the monsoon precipitation zone and the track of the East Asian winter monsoon during late Cenozoic. The integration of high-resolution geological record and numerical paleoclimate modeling could make new contributions to understanding the climate evolution and variation in eastern Asia in future studies. It could facilitate the investigation of the regional differences in East Asian environmental changes and the asynchronous nature between the uplift of Qinghai-Tibetan Plateau and their climatic effects. These would be the keys to understanding underlying driving forces for the evolution of the East Asian climate.

Understanding the response of ecosystems to past climate is critical for evaluating the impacts of future climate changes.A large-scale abrupt shift of vegetation in response to the Holocene gradual climate changes has been well documented for the Sahara-Sahel ecosystem. Whether such a non-linear response is of universal significance remains to be further addressed. Here,we examine the vegetation-climate relationships in central Asia based on a compilation of 38 high-quality pollen records. The results show that the Holocene vegetation experienced two major abrupt shifts, one in the early Holocene（Shift I, establishing shift） and another in the late Holocene（Shift II, collapsing shift）, while the mid-Holocene vegetation remained rather stable. The timings of these shifts in different regions are asynchronous, which are not readily linkable with any known abrupt climate shifts,but are highly correlated with the local rainfalls. These new findings suggest that the observed vegetation shifts are attributable to the threshold effects of the orbital-induced gradual climate changes. During the early Holocene, the orbital-induced precipitation increase would have first reached the threshold for vegetation ＂establishment＂ for moister areas, but significantly later for drier areas. In contrast, the orbital-induced precipitation decrease during the late Holocene would have first reached the threshold, and led to the vegetation ＂collapse＂ for drier areas, but delayed for moister areas. The well-known 4.2 kyr BP drought event and human intervention would have also helped the vegetation collapses at some sites. These interpretations are strongly supported by our surface pollen-climate analyses and ecosystem simulations. These results also imply that future climate changes may cause abrupt changes in the dry ecosystem once the threshold is reached.

MicroRNAs （miRNAs） are small endogenous RNAs molecules,approximately 21–23 nucleotides in length,which regulate gene expression by base-pairing with 3′ untranslated regions （UTRs） of target mRNAs.However,the functions of only a few miRNAs in organisms are known.Recently,the expression vector of artificial miRNA has become a promising tool for gene function studies.Here,a method for easy and rapid construction of eukaryotic miRNA expression vector was described.The cytoplasmic actin 3 （A3） promoter and flanked sequences of miRNA-9a （miR-9a） precursor were amplified from genomic DNA of the silkworm （Bombyx mori） and was inserted into pCDNA3.0 vector to construct a recombinant plasmid.The enhanced green fluorescent protein （EGFP） gene was used as reporter gene.The Bombyx mori N （BmN） cells were transfected with recombinant miR-9a expression plasmid and were harvested 48 h post transfection.Total RNAs of BmN cells transfected with recombinant vectors were extracted and the expression of miR-9a was evaluated by reverse transcriptase polymerase chain reaction （RT-PCR） and Northern blot.Tests showed that the recombinant miR-9a vector was successfully constructed and the expression of miR-9a with EGFP was detected.

Neogene eolian successions are one of the most important terrestrial palaeoenvironmental archives in East Asia.However, they have received far less attention than Quaternary loess deposits, especially in the case of lipid biomarker analysis.In order to obtain a better insight into the early-middle Miocene palaeoenvironment, we conducted a study of n-alkane biomarkers from sediments of the QA-I section（Qinan） in the western Chinese Loess Plateau, and compared the results with those of previous n-alkane analyses of eolian and aquatic sediments of varying age. Our principal results are as follows：（1） All QA-I samples contain n-alkanes ranging from C_（14） to C_（35）, among which the relative content of short-chain n-alkanes（C_（14）–C_（20）） from microorganisms is significantly greater than that of long-chain n-alkanes（C_（26）–C_（35）） from the waxes of terrestrial higher plants;the main peak is at C_（16）–C_（18）. All samples have a relatively lower abundance of medium-chain n-alkanes（C_（21）–C_（25）） than that of long-and short-chain n-alkanes, similar to strongly weathered palaeosols in Quaternary loess and Late Miocene-Pliocene Hipparion Red-Earth; however, this distribution is significantly different from that in weakly-weathered loess of Quaternary loess and Late Miocene-Pliocene Hipparion Red-Earth, as well as from aquatic sediments.（2） Despite some odd-over-even carbon predominance of long-chain n-alkanes in the QA-I samples, the carbon preference index（CPI） values are significantly lower than those of most of the weakly-weathered sediments. Our results show that strong weathering and microbial processes have significantly altered the n-alkanes in the Miocene eolian deposits in Qinan, and led to a significant oxidation and degradation of long-chain n-alkanes and the predominance of short-chain n-alkanes from bacteria. Therefore, the contribution of microorganism to total organic carbon（TOC） and its resulting in carbon isotopic composition should be carefully assessed in future studies.

MicroRNAs （miRNAs） are small endogenous RNAs molecules, approximately 21-23 nucleotides in length, which regulate gene expression by base-pairing with 3＇ untranslated regions （UTRs） of target mRNAs. However, the functions of only a few miRNAs in organisms are known. Recently, the expression vector of artificial miRNA has become a promising tool for gene function studies. Here, a method for easy and rapid construction ofeukaryotic miRNA expression vector was described. The cytoplasmic actin 3 （A3） promoter and flanked sequences of miRNA-9a （miR-9a） precursor were amplified from genomic DNA of the silkworm （Bombyx mori） and was inserted into pCDNA3.0 vector to construct a recombinant plasmid. The enhanced green fluorescent protein （EGFP） gene was used as reporter gene. The Bombyx mori N （BmN） cells were transfected with recombinant miR-9a expression plasmid and were harvested 48 h post transfection. Total RNAs of BmN cells transfected with recombinant vectors were extracted and the expression ofmiR-9a was evaluated by reverse transcriptase polymerase chain reaction （RT-PCR） and Northern blot. Tests showed that the recombinant miR-9a vector was successfully constructed and the expression of miR-9a with EGFP was detected.

The geomorphic evolution of northwestern China during the Cenozoic has been a subject of much geological interest because of its link with the uplift of the Himalayan-Tibetan complex. Much information about these changes is recoverable from the sedimentary sequences of the region. We report here on the thick eolian deposits mantling the Huajialing Mountains, a relatively flat mountain range in the western Loess Plateau. Correlation of magnetic susceptibility stratigraphy with the QA-I Miocene eolian sequence dates a 134.7 m section （NL-VII） for the interval from 18.7 to 11.8 Ma, as confirmed by micromammalian fossils. These eolian deposits demonstrate a much wider distribution of the Miocene eolian deposits, and also indicate that the topography contrasts in the western Loess Plateau, including the uplifts of the Huajialing Mountains and the bedrock highlands in the Qinan region, were formed by the early Miocene. The near-continuous Miocene eolian sequence from 18.7 to 11.8 Ma indicates that the substratum of Huajialing had not experienced any intense tectonic changes during this time interval, which suggests further, the relative tectonic stability of the nearby Tibetan Plateau.

Chiral nano-assemblies with amplified optical activity have attracted particular interest for their potential application in photonics, sensing and catalysis. Yet it still remains a great challenge to realize their real applications because of the instability of these assembled nanostructures. Herein, we demonstrate a facile and efficient method to fabricate ultra-stable chiral nanostructures with strong chiroptical properties. In these novel chiral nanostructures, side-by-side assembly of chiral cysteine-modified gold nanorods serves as the core while mesoporous silica acts as the shell. The chiral core-shell nanostructures exhibit an evident plasmonic circular dichroism （CD） response originating from the chiral core. Impressively, such plasmonic CD signals can be easily manipulated by changing the number as well as the aspect ratio of Au nanorods in the assemblies located at the core. In addition, because of the stabilization effect of silica shells, the chiroptical performance of these core-shell nanostructures is significantly improved in different chemical environments.

Infections by coronaviruses such as severe acute respiratory syndrome （SARS） coronavirus （SCoV） and mouse hepatitis virus A59 （MHV-A59） result in very little type I interferon （IFN） production by host cells, which is potentially responsible for the rapid viral growth and severe immunopathology associated with SARS. However, the molecular mechanisms for the low IFN production in cells infected with coronaviruses remain unclear. Here, we provide evidence that Papain-like protease domain 2 （PLP2）, a catalytic domain of the nonstructural protein 3 （nsp3） of MHV-A59, can bind to IRF3, cause its deubiquitination and prevent its nuclear translocation. As a consequence, co-expression of PLP2 strongly inhibits CARDIF-, TBK1- and IRF3-mediated IFNp reporter activities. In addition, we show that wild-type PLP2 but not the mutant PLP2 lacking the deubiquitinase （DUB） activity can reduce IFN induction and promote viral growth in cells infected with VSV. Thus, our study uncovered a viral DUB which coronaviruses may use to escape from the host innate antiviral responses.