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AbstractLung cancer remains one of the most common malignant cancers worldwide, and its survival rate is extremely low. Chemotherapy, the mainstay of lung cancer treatment, is not as effective as it could be due to the development of cellular resistance. The molecular mechanisms of drug resistance in lung cancer remain to be elucidated. Accumulating evidence suggests that ceRNAs are involved in various carcinogenesis and development. CeRNA is a transcript that regulates each other through competition with miRNA. However, the relationship between ceRNAs and chemoresistance in lung cancer remains unclear. In this narrative review, we provided a summary of treatment approaches that focus on ceRNA networks to overcome drug resistance.

Millet agriculture, which originated in northern China, alongside rice agriculture, have nurtured the Chinese civilization. Prehistoric manuring practices likely promoted and maintained sustainable millet agricultural production in the loess area of northern China. However, ongoing controversy exists regarding the indicators of prehistoric manuring intensity of foxtail millet (Setaria italica) and common millet (Panicum miliaceum). Here, we present the results of pot and field fertilization experiments on two millet types. Our findings suggest that manuring can significantly increase the δ15N values of foxtail millet, and its δ15N values increase with increasing manuring levels. The δ15N values of foxtail millet leaves are systematically greater than those of grains by approximately 1.6‰. Manuring could have a long-term residual impact on increasing the δ15N values of soil and millet crops. Combined with previous crop fertilization experiment results, we propose that the impact of manuring on the δ15N values of non-nitrogen-fixing crops is roughly consistent. The δ15N value and amount of manure are key factors determining the extent of change in plant δ15N values. The millet grain δ15N values can serve as reliable indicators of manuring practices. Finally, we provide an interpretive framework for assessing the correlation between manuring levels and the δ15N values of archaeological millet remains. The δ15N values of ancient millet grains suggest widespread and intensive manuring practices in prehistoric millet agriculture in northern China, spanning from the early Yangshao period to the Longshan period.

ABSTRACTBackgroundThis study aimed to assess the association between drug-induced liver injury (DILI) and antibody-drug conjugates (ADCs) by comprehensively evaluating spontaneous reports submitted to the Food and Drug Administration Adverse Event Reporting System (FAERS) database from 2004Q1 to 2022Q3.Research design and MethodsAll DILI cases with ADCs as primary suspected drugs were extracted from the FAERS database from 2004Q1 to 2022Q3 using OpenVigil 2.1. The reporting odds ratio (ROR) and the proportional reporting ratio (PRR) for reporting the association between different drugs and DILI risk were calculated.ResultsA total of 504 DILI cases were attributed to ADCs during the study period. Patients with ADCs-related DILI (n = 504) had a mean age of 56.2 ± 18.4 years, with 167 cases not reporting patients’ age. Females and males comprised 42.5% and 44.0% of the cases, respectively, while there was no information on gender in 13.5% of the cases. The DILI signals were detected in trastuzumab emtansine, enfortumab vedotin, brentuximab vedotin, polatuzumab vedotin, gemtuzumab ozogamicin, inotuzumab ozogamicin, and trastuzumab deruxtecan.ConclusionsThe FAERS data mining suggested an association between DILI and some ADCs. Further studies are warranted to unraveling the underlying mechanisms and taking preventive measures for ADCs-related DILI.

AbstractThe goal of the article is to better understand cosupport in triangulated categories since it is still quite mysterious. We study boundedness of local cohomology and local homology functors using Koszul objects, give some characterizations of cosupport, and get some results that, in special cases, recover and generalize the known results about the usual cosupport. Additionally, we include some computations of cosupport and provide a comparison of support and cosupport for cohomologically finite objects. Finally, we assign to any object of the category a subset of $\mathrm {Spec}R$ , called the big cosupport, and study some of its properties.

RNA molecules perform various crucial roles in diverse cellular processes, from translating genetic information to decoding the genome, regulating gene expression and catalyzing chemical reactions. RNA-binding proteins (RBPs) play an essential role in regulating the diverse behaviors and functions of RNA in live cells, but techniques for the spatiotemporal control of RBP activities and RNA functions are rarely reported yet highly desirable. We recently reported the development of LicV, a synthetic photoswitchable RBP that can bind to a specific RNA sequence in response to blue light irradiation. LicV has been used successfully for the optogenetic control of RNA localization, splicing, translation and stability, as well as for the photoswitchable regulation of transcription and genomic locus labeling. Compared to classical genetic or pharmacologic perturbations, LicV-based light-switchable effectors have the advantages of large dynamic range between dark and light conditions and submicron and millisecond spatiotemporal resolutions. In this protocol, we provide an easy, efficient and generalizable strategy for engineering photoswitchable RBPs for the spatiotemporal control of RNA metabolism. We also provide a detailed protocol for the conversion of a CRISPR–Cas system to optogenetic control. The protocols typically take 2–3 d, including transfection and results analysis. Most of this protocol is applicable to the development of novel LicV-based photoswitchable effectors for the optogenetic control of other RNA metabolisms and CRISPR–Cas functions.

CircRNA is stable due to its ring structure and is abundant in humans, which not only exists in various tissues and biofluids steadily but also plays a significant role in the physiology and pathology of human beings. CircPVT1, an endogenous circRNA, has recently been identified from the PVT1 gene located in the cancer risk region 8q24. CircPVT1 is reported to be highly expressed in many different tumors, where it affects tumor cell proliferation, apoptosis, invasion, and migration. We summarize the biosynthesis and biological functions of circPVT1 and analyze the relationship between circPVT1 and tumors as well as its significance to tumors. Further, it's noteworthy for the diagnosis, treatment, and prognosis of cancer patients. Therefore, circPVT1 is likely to become an innovative tumor marker.

A sensitive photoelectrochemical (PEC) biosensor for silver ions (Ag+) was developed based on Zn–Co doped C and CdS quantum dot (CdS QD) nanomaterials. Hydrophobic modified sodium alginate (HMA), which could stabilize and improve the PEC performance of CdS QDs, was also used for the construction of PEC sensors. Especially, Zn–Co doped C, CdS QDs and HMA were sequentially modified onto an electrode surface viathe drop-coating method, and a C base rich DNA strand was then immobilized onto the modified electrode. As the C base in DNA specifically recognized Ag+, it formed a C–Ag+–C complex in the presence of Ag+, which created a spatial steric hindrance, resulting in a reduced PEC response. The sensing platform is sensitive to Ag+in the range of 10.0 fM to 0.10 μM, with a limit of detection of 3.99 fM. This work offers an ideal platform to determine trace heavy metal ions in environmental monitoring and bioanalysis.

Complex databases are challenging to explore and query by users unfamiliar with their schemas. Enterprise databases often have hundreds of inter-linked tables, so even when extensive documentation is available, new users must spend a considerable amount of time understanding the schema before they can retrieve any information from the database. The problem is aggravated if the documentation is missing or outdated, which may happen with legacy databases.In this paper we identify limitations of previous approaches to address this vexing problem, and propose a principled approach to summarizing the contents of a relational database, so that a user can determine at a glance the type of information it contains, and the main tables in which that information resides. Our approach has three components: First, we define the importance of each table in the database as its stable state value in a random walk over the schema graph, where the transition probabilities depend on the entropies of table attributes. This ensures that the importance of a table depends both on its information content, and on how that content relates to the content of other tables in the database. Second, we define a metric space over the tables in a database, such that the distance function is consistent with an intuitive notion of table similarity. Finally, we use a Weighted k-Center algorithm under this distance function to cluster all tables in the database around the most relevant tables, and return the result as our summary. We conduct an extensive experimental study on a benchmark database, comparing our approach with previous methods, as well as with several hybrid models. We show that our approach not only achieves significantly higher accuracy than the previous state of the art, but is also faster and scales linearly with the size of the schema graph.

MiRNAs are confirmed to be a kind of short and eminently conserved noncoding RNAs, which regulate gene expression at the post-transcriptional level via binding to the 3'- untranslated region (3’-UTR) of targeting multiple target messenger RNAs. Recently, growing evidence stresses the point that they play a crucial role in a variety of pathological processes, including human cancers. Dysregulated miRNAs act as oncogenes or tumor suppressor genes in many cancer types. Among them, we noticed that miR-122 has been widely reported to significantly influence carcinogenicity in a variety of tumors by regulating target genes and signaling pathways. Here, we focused on the expression of miR-122 in regulatory mechanisms and tumor biological processes. We also discussed the effects of miR-122 dysregulation in various types of human malignancies and the potential to develop new molecular miR-122-targeted therapies. The present review suggests that miR-122 may be a potentially useful cancer diagnosis and treatment biomarker. More clinical diagnoses need to be further launched in the future. A promising direction to improve the outcomes for cancer patients will likely combine miR-122 with other traditional tumor biomarkers.

Ecosystems in high-altitude regions are more sensitive and respond more rapidly than other ecosystems to global climate warming. The Qinghai-Tibet Plateau (QTP) of China is an ecologically fragile zone that is sensitive to global climate warming. It is of great importance to study the changes in aboveground biomass and species diversity of alpine meadows on the QTP under predicted future climate warming. In this study, we selected an alpine meadow on the QTP as the study object and used infrared radiators as the warming device for a simulation experiment over eight years (2011–2018). We then analyzed the dynamic changes in aboveground biomass and species diversity of the alpine meadow at different time scales, including an early stage of warming (2011–2013) and a late stage of warming (2016–2018), in order to explore the response of alpine meadows to short-term (three years) and long-term warming (eight years). The results showed that the short-term warming increased air temperature by 0.31°C and decreased relative humidity by 2.54%, resulting in the air being warmer and drier. The long-term warming increased air temperature and relative humidity by 0.19°C and 1.47%, respectively, and the air tended to be warmer and wetter. The short-term warming increased soil temperature by 2.44°C and decreased soil moisture by 12.47%, whereas the long-term warming increased soil temperature by 1.76°C and decreased soil moisture by 9.90%. This caused the shallow soil layer to become warmer and drier under both short-term and longterm warming. Furthermore, the degree of soil drought was alleviated with increased warming duration. Under the long-term warming, the importance value and aboveground biomass of plants in different families changed. The importance values of grasses and sedges decreased by 47.56% and 3.67%, respectively, while the importance value of weeds increased by 1.37%. Aboveground biomass of grasses decreased by 36.55%, while those of sedges and weeds increased by 8.09% and 15.24%, respectively. The increase in temperature had a non-significant effect on species diversity. The species diversity indices increased at the early stage of warming and decreased at the late stage of warming, but none of them reached significant levels (P>0.05). Species diversity had no significant correlation with soil temperature and soil moisture under both short-term and long-term warming. Soil temperature and aboveground biomass were positively correlated in the control plots (P=0.014), but negatively correlated under the long-term warming (P=0.013). Therefore, eight years of warming aggravated drought in the shallow soil layer, which is beneficial for the growth of weeds but not for the growth of grasses. Warming changed the structure of alpine meadow communities and had a certain impact on the community species diversity. Our studies have great significance for the protection and effective utilization of alpine vegetation, as well as for the prevention of grassland degradation or desertification in high-altitude regions.

AbstractIn the process of chemotherapy, drug resistance of cancer cells is a common and difficult problem of chemotherapy failure, and it is also the main cause of cancer recurrence and metastasis. Non-coding RNAs (ncRNAs) refer to the RNA that does not encode proteins, including microRNA (miRNA), long non-coding RNA (lncRNA) and circularRNA (circRNA), etc. NcRNAs are involved in a series of important life processes and further regulate the expression of ABCC1 by directly or indirectly up-regulating or down-regulating the expression of targeted mRNAs, making cancer cells more susceptible to drug resistance. A growing number of studies have shown that ncRNAs have effects on cancer cell proliferation, invasion, metastasis, and drug sensitivity, by regulating the expression of ABCC1. In this review, we will discuss the emerging roles of ncRNAs regulating ABCC1 in chemotherapy resistance and mechanisms to reverse drug resistance as well as provide potential targets for future cancer treatment.

Tiny objects in satellite videos are usually not independent individuals; there exist rich semantic and temporal relations with each other. Thus, modeling and reasoning the variation of such intrinsic relationships can be beneficial for tiny object tracking. In this article, a relation learning reasoning method is proposed for tiny object tracking in satellite videos. The core of the proposed is the relation reasoning network that consists of a key context module, a global semantic module, and a relation reasoning module sequentially. First, the key context module exploits global key contexts which explicitly or implicitly contribute to the target object, modeling the intrinsic relations with the target. Second, to reason the contribution, the global semantic module analyses the interaction between them in the same frame. Third, the relation reasoning module deduces the target based on the variation of the semantic relations among different frames. Such a relation learning reasoning approach which takes the target as the core is aligned with the satellite tiny object tracking task, significantly improves the identification performance in dense similarity (DS) scenes and the retrieval ability after completely occluded. Furthermore, the proposed method is shown to report improved qualitative and quantitative results on Jilin-1 and SkySat satellite video datasets.

Multifunctionalization from the interception of active intermediates is an attractive synthetic strategy for the efficient construction of complex molecular scaffolds in an atom and step economic fashion. However, the design of reactions involving metal carbynoids that exhibit carbene/carbocation behavior is currently limited, and developing catalyst-controlled highly enantioselective versions poses significant challenges. In this study, we present the first asymmetric trifunctionalization reactions with rhodium carbynoids. This reaction unveils the distinctive reactivity of the carbynoid precursor, enabling it to react with simultaneously two nucleophiles and one electrophile. This process involves the formation of two distinct carbene ylides with the alcohol/carbamate and the trapping of one ylide with the imine, resulting in the formation of three new bonds. Furthermore, this strategy allows for the divergent synthesis of a wide array of β-amino esters in high yields and exceptional enantioselectivity.

Introduction: Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and dolutegravir plus lamivudine (DTG + 3TC) are well tolerated and effective in clinical trials. This study aimed to evaluate the safety and efficacy of these two schemes in a real-world setting and to obtain the first dataset for switching to BIC/FTC/TAF and DTG + 3TC in a Chinese population. Methods: This retrospective single-center cohort study in China included participants who switched to DTG + 3TC or BIC/FTC/TAF between January 2020 and February 2023. The main endpoint was the proportion of participants with HIV-1 RNA levels of ≥ 50 copies/mL. Safety, tolerance, and the incidence of low-level viremia (LLV) were evaluated. Results: A total of 525 participants were included, 454 of whom were included in the PP analysis. At week 48, the proportions of participants with HIV-1 RNA ≥ 50 copies/mL were 4.4% (10/225) for DTG + 3TC and 6.1% (14/229) for BIC/FTC/TAF; virological efficacy did not differ significantly between the two groups. Consistent results were obtained in an intent-to-treat (ITT) analysis. The incidences of LLV were 3.6% (7/193) and 4.9% (10/206), respectively. During the study, none of the participants stopped taking drugs because of a lack of efficacy or adverse reactions. Conclusions: Both regimens are well tolerated and effective for switching HIV-1 infection therapy. However, the detection of genotypic drug resistance should be considered when baseline virological non-suppression is observed.

Three-dimensional (3D) cell culture methods have been validated that can replicate the tumor environment in vivo to a large extent, providing an effective tool for studying tumors. In this study, we demonstrated the use of standard laboratory pipette tips as micro vessels for generating 3D cell spheroids. No microfabrication or wet-chemistry surface modifications were involved in the procedure. Spheroids consisting of single or multiple cell types were generated within 24 h just by pipetting and incubating a cell suspension in pipette tips. Scanning electron microscope and optical microscope proved that the cells grew together tightly, and suggested that while gravity force might have initiated the sedimentation of cells at the bottom of the tip, the active aggregation of cells to form tight cell-cell interactions drove the formation of spheroids. Using common laboratory micropipettes and pipette tips, the rate of spheroid generation and the generation reproducibility was characterized from five boxes each with 80 tips. The ease of transferring reagents allowed modeling of the growth of microvascular endothelial cells in tumor spheroids. Moreover, the pairing and fusion of tumor spheroids could be manipulated in the pipette tips, suggesting the potential for building and assembling heterogeneous micro-tumor tissues in vitro to mimic solid tumors in vivo. This study demonstrated that spheroids can be readily and cost-effectively generated in standard biological laboratories in a timely manner using pipette tips.

Graphical AbstractAdherence to a healthy lifestyle in different genetic backgrounds is significantly associated with a lower risk of VHD. AS, aortic stenosis; GR, genetic risk; HR, hazard ratio; VHD, valvular heart disease; SD, standard deviation.

The transition of human societies from high mobility to sedentary lifestyles had a profound impact on subsistence, technology, and the origin of civilization. Sedentism was influenced by various factors such as climate change, population growth, resource pressure, and technological innovation. The Tibetan Plateau, due to its alpine and hypoxic conditions, is an ideal region to study human adaptation to extreme environments. However, the prehistoric process of sedentism on the Tibetan Plateau is unclear and the chronological sequence and driving mechanism of sedentism on the Tibetan Plateau are still controversial. Previous studies have focused on the diffusion of agriculture from low to high elevation areas, with little attention given to the role of animal resources in sedentism. Seasonality analysis using animal remains is crucial in determining whether a site was occupied year-round. To establish the seasonal calendar of animal resource utilization, it is recommended to create a database of skeletal morphology, whole genome, and proteome of contemporary Tibetan Plateau fauna to aid in the identification of animal remains from archaeological sites. Thus, intricate web of human-animal-environment relationship and the role of animal resources in human sedentism on the Tibetan Plateau can then be evaluated.

Abstract: In this study, a sensitive photoelectrochemical immunosensor with dye-enhanced anodic photocurrent response was proposed for sensitive detection of α-fetoprotein (AFP). Specifically, europium-doped TiO2(Eu-TiO2) was used as the photoelectrochemical functional material and coated onto indium tin oxide (ITO) electrode. Doxorubicin (DOX) as an excellent fluorescent dye was encapsulated in the hydrophobically modified alginate (HMA). Then the dye-loaded HMA was modified onto the surface of Eu-TiO2to further sensitize the photocurrent response. The results showed that the photoelectrical signal was enhanced and stabilized due to the effect of sensitization of DOX on Eu-TiO2material. The constructed PEC sensor revealed a good linear response to AFP antigen ranging from 0.5 to 100 ng/mL with a detection limit of 0.41 pg/mL. The clinical patient’s serum test results obtained from the proposed PEC immunosensor were consistent with those obtained from the commercial electrochemilunescence assay. The proposed PEC sensing method could be a promising analytical tool for the detection of AFP in clinical analysis. Graphical abstract:

The southern spread of rice agriculture is of great academic interest. Although it already has a broad chronological framework, newly introduced rice use and its impact on local subsistence and ecological systems are still unclear. In this study, we explore these issues by analysing phytoliths recovered from continuous sediments of Cave No. 4 at the Nanshan site in Fujian Province, together with evidence from surrounding sites. The results show that rice was introduced into southeast China at 7,500 cal. yr BP, but the dominance of the hunting-gathering system was not challenged until later, between 5,000 and 3,500 cal. yr BP, when cultivation of rice, together with foxtail and broomcorn millets, was widely practiced in the region. This suggests that mixed farming in Southeast China, likely originating around the middle Yangtze River, became widespread and gradually systematic during the previous two-millennium adoption. This rice-millet mixed agricultural system changed the former hunting-gathering subsistence system, promoting the agriculturalization process, cultural prosperity and population growth, thus providing a solid basis for rice expansion and cultural migration to Southeast Asia.

Graphical abstract: A simple, label- and hairpin-free fluorescent system based on spherical identification probe and toehold-mediated strand displacement reaction-initiated silver nanoclusters (AgNCs) “on–off” signal switch was successfully constructed to detect target DNA.

With hot water extraction and ethanol precipitation, three high molecular weight polysaccharides, LZLs (LZL-1, LZL-2 and LZL-3), were successfully purified from the edible bulbs of Lanzhou lily by DEAE-52 cellulose and sephadex G-200 column. The structure features of LZLs were characterized by gas chromatography, scanning electron microscope, high performance gel-permeation chromatography, IR and NMR, and the antioxidant activities of LZLs were assayed. The results showed that LZL-1, LZL-2 and LZL-3 were composed of glucose and mannose with the molar ratios of 2.4:2.5, 2.6:2.5 and 2.2:2.5, while their molecular weights were 2.33 × 106, 1.92 × 106and 1.26 × 106, respectively. LZLs were mainly α-pyranose configurations with lamellar structure and triple helix conformation except LZL-3. LZLs had similar glycosidic linkage patterns with main substitution at O-6 of glucose or mannose but the different substitution positions at O-3 of them. Vitro bioassays showed that LZLs had effective scavenging abilities to free radicals, especially to DPPH and hydroxyl radicals. When the concentration reached 4 mg/mL, the scavenging rate of LZLs to DPPH and hydroxyl radicals were up to 60% and 70%, respectively. These findings provided more references for potential applications of Lanzhou lily polysaccharides as natural antioxidant agents in food and pharmaceuticals.

The aim of this study was to investigate the effects of low-protein diets and the sustained release of synthetic amino acids (AA) on the performance, intestinal barrier function and nitrogen excretion of laying hens. Two hundred eighty-eight 39-week-old Hyline brown laying hens of were randomly divided into 3 groups with 8 replicates per group. The crude protein level in the control group (CON) was 16%, the crude protein levels in the crystal AA supplement group (LCP-CAA) and microencapsulated AA group (LCP-MAA) were both 13%, and the AA levels in the LCP-CAA and LCP-MAA groups were consistent with that in the CON group. The experiment lasted 12 wk, and production performance was assessed weekly. The FCR and ADFI values were significantly greater for the LCP-CAA group than for the CON and LCP-MAA groups (P< 0.05). Two hours after feeding, His levels were significantly greater in the LCP-CAA group than in the LCP-MAA group (P< 0.05); 4 h after feeding, the contents of Met, Thr, Leu and Val were significantly greater in blood from the LCP-MAA group (P< 0.05); 6 h after feeding, Trp, Ile and Arg levels were significantly greater in the LCP-MAA group (P< 0.05). The chylase content significantly decreased in the duodenum of the LCP-CAA group (P< 0.05), and the chylase and trypsin were contents increased in the ileum of the LCP-MAA group (P< 0.05). In the LCP-MAA group, significantly increased mRNA expression levels of Occludin, ZO-1 in duodenum; Occludin, ZO-1, y+LAT1 in jejunum; and ZO-1 in ileum were detected at 8 and 12 weeks (P< 0.05). The fecal nitrogen content significantly decreased in the low protein diet group (P< 0.01). In conclusion, reducing dietary crude protein levels and supplementing with microencapsulated AAs can improve intestinal barrier function, promote digestive enzyme secretion, increase the expression of AA transporters, improve dietary protein utilization efficiency, and reduce nitrogen emission in laying hens.

•The archaeobotanical findings indicated that Guye people have heavily relied on arboreal foodstuffs in south China, 5900–5400 BP.•The subsistence system presents a schedule centred on summer and autumn, according to the fruiting seasonality of recovered plant remains.•Well-scheduled subsistence and affluent resources in South China may delay the adoption process of exotic cereal cultivation.

The ZIF-67 reinforced the interaction at the interface between PTAA and perovskite, enhances the adhesion and improves the charge carrier transport, resulting in an increase in the efficiency and stability of inventing f-PSCs.

Simultaneous inhibition of tumor vasculature and the glycolysis pathway may be a targeted anti-tumor strategy to inhibit tumor nutrient supply. Flavonoids are natural products with strong biological activity, which inhibit hypoxia induction factor 1α (HIF-1α) regulating glycolysis and tumor angiogenesis, while salicylic acid can reduce the glycolysis level of tumor cells by inhibiting related rate-limiting enzymes. A series of salicylic acid-modified indole trimethoxy-flavone derivatives were designed and synthesized by introducing benzotrimethoxy-structure commonly used in blood vessel blockers, and their anti-tumor activities were evaluated. Among them, compound 8fexhibited significant anti-proliferative activity against two hepatoma cells, HepG-2 and SMMC-7721, with IC50values of 4.63 ± 1.13 μM and 3.11 ± 0.35 μM, respectively. Colony formation experiments also further verified its excellent in vitroanti-tumor activity. In addition, compound 8fshowed the ability to induce apoptosis in SMMC-7721 cells in a concentration-dependent manner. After treatment with compound 8f, the expressions of the rate-limiting enzymes PKM2, PFKM, HK2 and tumor angiogenesis-related vascular endothelial growth factor of the glycolytic pathway were all down-regulated, and the lactate level in the hepatoma cell SMMC-7721 was significantly reduced. The morphology of the nucleus and tubulin was also observed to disperse gradually with the increase of compound 8fconcentration. And compound 8fshowed strong binding ability to tubulin. Our results suggest that the strategy of synthesizing the salicylic acid-modified indole flavone derivative 8fis a way to obtain active anti-tumor candidate compounds that may be further developed as targeted agents to inhibit tumor vasculature and glycolytic pathways.

Traditional zooarchaeological and archaeobotanical methods based on morphological identification of the excavated faunal and floral remains have been broadly used in reconstructing ancient subsistence economies. However, the accuracy and reliability of these methods rely heavily on the preservation state of the remains. By sequencing the ancient DNA of plants, animals, and microorganisms preserved in sediment, sedimentary ancient DNA (sedaDNA) now offers a novel approach for reconstructing the taxa composition dated back to hundreds of thousands of years. Yet, its application in open-air archaeological sites is rarely reported. In this study, we attempted to apply sedaDNA shotgun metagenomics on the archaeological deposits of the Khog Gzung site (an open-air site dated to 3160–2954 cal yr BP) on the Tibetan Plateau, and then compared the reconstructed taxonomic composition to the unearthed remains. Results showed that most of the crops and domestic animals identified by the two approaches, such as barley (Hordeum vulgare) and sheep (Ovis aries), are in general consistent. Some species, such as foxtail millet (Setaria italica), however, was only detected by sedaDNA. In addition, a variety of microorganisms were also detected by the sedaDNA. The two approaches combined revealed diversified food recourses at the Khog Gzung site, which included crops such as millet, barley and wheat, domestic animals such as sheep and cattle, and likely also wild animals from fishing and hunting. Our data proves that sedaDNA has a great potential in reconstructing the faunal and floral compositions from archaeological deposits, therefore laying the foundation for its border applications.

Shape memory alloy (SMA) wires are one of the widely used materials for soft artificial muscles. However, SMA artificial muscles have two problems, including limited load holding ability due to their soft nature and slow response due to their long cooling time. The main contributions of this article are the developments of a controllable magnetorheological fluid (MRF) exoskeleton and a fast-response magnetorheological elastomer-SMA artificial muscle as effective approaches to solve the above-mentioned problems. The controllable MRF exoskeleton provides variable stiffness so that it can be flexible enough to allow the manipulator to bend as required while stiff enough to hold up heavy loads. This new artificial muscle accelerates the cooling speed of SMA wire to shorten its recovery time. Our tests proved that this new artificial muscle, compared with conventional SMA artificial muscles, could improve the recovery speed by up to 333%. The new artificial muscle and the MRF exoskeleton assembled a robotic manipulator and then a robotic gripper with three of those manipulators. The experimental tests verified that the loading capability of the new gripper had increased by 440% compared to the pure SMA gripper.

Artificial vesicles for mimicking the unique structures and functions of natural organelles represent a promising scientific object in biomimicry. However, the development of the stimuli-responsive and ultrathin vesicles assembled from sequence-defined biomimetic polymers for controllable applications is still a significant challenge. Herein, we report the self-assembly of azobenzene-based amphiphilic alternating peptoids to generate photo-responsive and ultrathin peptoid vesicle (pepsomes) with an average diameter of ∼180 nm. Both cryo-transmission electron microscopy (TEM) and dissipative particle dynamics simulation proved that the vesicular membrane was the ultrathin bilayer structure around ∼1.6 nm. The photo-responsive ability of pepsomes was demonstrated by the reversible size changes upon the alternative irradiation with ultraviolet (UV) and visible lights, which was attributable to the photoisomerization virtue of azobenzene moiety. As a proof-of-concept, the photo-controllable catalytic action of gold nanoparticles-decorated pepsomes was evaluated toward the borohydride-mediated reduction from 4-nitrophenol to 4-aminophenol. Photo-controllable reversible and recyclable catalytic activity was effectively modulated using the alternative irradiation with UV and visible lights for five cycles. Our work provides a simple strategy to prepare stimuli-responsive and ultrathin vesicles for potential application on nanocatalysis.

ABSTRACTObjectivesTo compare the pharmacokinetics (PK), pharmacodynamics (PD), safety, and immunogenicity of LY06006 (denosumab biosimilar) and denosumab in healthy Chinese adult male subjects.MethodsIn this randomized, double-blind, parallel-controlled, single-dose, comparative biosimilar study, a total of 168 subjects received 60 mg of LY06006 or denosumab by subcutaneous (SC) abdominal injections in a 1:1 ratio with a follow-up period of 168 days.ResultsAfter a single SC abdominal injection of 60 mg LY06006/denosumab, the geometric mean ratio of the main pharmacokinetic parameters, Cmaxand AUC0-∞,of the two drugs were 97.57% and 104.27%, respectively; the geometric mean ratio of the main pharmacodynamic parameters AUEC0-tand Emax, were 101.00% and 99.64%, respectively, and the 90% confidence interval was observed to be within 80–125%. The subjects in the test group (LY06006) and control group (denosumab) were all negative for anti-drug antibody (ADA). The incidence and severity of treatment-emergent adverse events (TEAEs)were similar for both groups, and no grade 3 or higher TEAEs occurred in either group.ConclusionsThis study demonstrated that LY06006 and denosumab have similar characteristics and bioequivalence in pharmacokinetics. Moreover, they had similar pharmacodynamic profiles, safety, and immunogenicity.Clinical trial registrationwww.clinicaltrials.govidentifier is NCT04973722

ABSTRACTObjectiveHS-20090 is a proposed biosimilar candidate of Denosumab (Xgeva®). The study aimed to evaluate the similarity of pharmacokinetics (PK), pharmacodynamics (PD), safety, and immunogenicity between HS-20090 and Xgeva® in healthy Chinese subjects.MethodsA single-center, randomized, double-blinded, active-controlled study was conducted in healthy Chinese adult male subjects. A total of 154 subjects were planned to be randomly assigned (1:1) to receive 120 mg of either HS-20090 or Xgeva® in a single subcutaneous injection, with a follow-up period of 155 days. The primary objective was to evaluate the bioequivalence of PK. The primary endpoints were Cmaxand AUC0-∞. The secondary objectives were to evaluate the similarity of PD, safety, and immunogenicity.ResultsAll 154 subjects were included in the PK, PD, and safety analyses. The 90% CIs of GMRs of HS-20090/Xgeva® for Cmax, AUC0-t, and AUC0-∞were 90.49 ~ 100.23%, 94.45 ~ 104.61%, and 94.08 ~ 105.23%, respectively, achieving the bioequivalence criteria of 80 ~ 125%. The PD parameters and incidence of adverse events between HS-20090 and denosumab were also similar, with no detection of ADA in both the groups.ConclusionHS-20090 was highly similar to Xgeva®, with regard to PK, PD, safety profiles, and immunogenicity in healthy Chinese subjects. These data support subsequently comparative clinical study for bone metastases in solid tumors.Clinical trial registrationwww.clinicaltrials.govidentifier is NCT04494373.