DR30318, a novel tri-specific T cell engager for Claudin 18.2 positive cancers immunotherapy.

BACKGROUND: Claudin 18.2 (CLDN18.2) is a highly anticipated target for solid tumor therapy, especially in advanced gastric carcinoma and pancreatic carcinoma. The T cell engager targeting CLDN18.2 represents a compelling strategy for enhancing anti-cancer efficacy. METHODS: Based on the in-house screened anti-CLDN18.2 VHH, we have developed a novel tri-specific T cell engager targeting CLDN18.2 for gastric and pancreatic cancer immunotherapy. This tri-specific antibody was designed with binding to CLDN18.2, human serum albumin (HSA) and CD3 on T cells. RESULTS: The DR30318 demonstrated binding affinity to CLDN18.2, HSA and CD3, and exhibited T cell-dependent cellular cytotoxicity (TDCC) activity in vitro. Pharmacokinetic analysis revealed a half-life of 22.2-28.6 h in rodents and 41.8 h in cynomolgus monkeys, respectively. The administration of DR30318 resulted in a slight increase in the levels of IL-6 and C-reactive protein (CRP) in cynomolgus monkeys. Furthermore, after incubation with human PBMCs and CLDN18.2 expressing cells, DR30318 induced TDCC activity and the production of interleukin-6 (IL-6) and interferon-gamma (IFN-γ). Notably, DR30318 demonstrated significant tumor suppression effects on gastric cancer xenograft models NUGC4/hCLDN18.2 and pancreatic cancer xenograft model BxPC3/hCLDN18.2 without affecting the body weight of mice.

Nitrogen addition does not alter symmetric responses of soil respiration to changing precipitation in a semi-arid grassland.

Concurrent changing precipitation regimes and atmospheric nitrogen (N) deposition can have profound influences on soil carbon (C) cycling. However, how N enrichment regulates the responses of soil C fluxes to increasing variability of precipitation remains elusive. As part of a field precipitation gradient experiment with nine levels of precipitation amounts (-60 %, -45 %, -30 %, -15 %, ambient precipitation, +15 %, +30 %, +45 %, and +60 %) and two levels of N addition (0 and 10 g N m-2 yr-1) in a semi-arid temperate steppe on the Mongolian Plateau, this work was conducted to investigate the responses of soil respiration to decreased and increased precipitation (DP and IP), N addition, and their possible interactions. Averaged over the three years from 2019 to 2021, DP suppressed soil respiration by 16.1 %, whereas IP stimulated it by 27.4 %. Nitrogen addition decreased soil respiration by 7.1 % primarily via reducing microbial biomass C. Soil respiration showed symmetric responses to DP and IP within all the four precipitation variabilities (i.e., 15 %, 30 %, 45 %, and 60 %) under ambient N. Nevertheless, N addition did not alter the symmetric responses of soil respiration to changing precipitation due to the comparable sensitivities of microbial biomass and root growth to DP and IP under the N addition treatment. These findings indicate that intensified precipitation variability does not change but N addition could alleviate soil C releases. The unchanged symmetric responses of soil respiration to precipitation variability under N addition imply that N deposition may not change the response pattern of soil C releases to predicted increases in precipitation variability in grasslands, facilitating the robust projections of ecosystem C cycling under future global change scenarios.

An innovative antibody fusion protein targeting PD-L1, VEGF and TGF-ß with enhanced antitumor efficacies.

Immunosuppressive pathways in the tumor microenvironment (TME) are inextricably linked to tumor progression. Mono-therapeutics of immune checkpoint inhibitors (ICIs, e.g. antibodies against programmed cell death protein-1/programmed cell death ligand-1, PD-1/PD-L1) is prone to immune escape while combination therapeutics tends to cause high toxicity and side effects. Therefore, using multi-functional molecules to target multiple pathways simultaneously is becoming a new strategy for cancer therapies. Here, we developed a trifunctional fusion protein, DR30206, composed of Bevacizumab (an antibody against VEGF), and a variable domain of heavy chain of heavy chain antibody (VHH) against PD-L1 and the extracellular domain (ECD) protein of TGF-ß receptor II (TGF-ß RII), which are fused to the N- and C-terminus of Bevacizumab, respectively. The original intention of DR30206 design was to enhance the immune responses pairs by targeting PD-L1 while inhibiting VEGF and TGF-ß in the TME. Our data demonstrated that DR30206 exhibits high antigen-binding affinities and efficient blocking capabilities, the principal drivers of efficacy in antibody therapy. Furthermore, the capability of eliciting antibody-dependent cellular cytotoxicity (ADCC) and mixed lymphocyte reaction (MLR) provides a greater possibility to enhance the immune response. Finally, in vivo experiments showed that the antitumor activity of DR30206 was superior to those of monoclonal antibody of PD-L1 or VEGF, PD-L1 and TGF-ß bispecific antibody or the combination inhibition of PD-L1 and VEGF. Our findings suggest there is a great potential for DR30206 to become a therapeutic for the treatment of multiple cancer types, especially lung cancer, colon adenocarcinoma and breast carcinoma.

Cropland abandonment alleviates soil carbon emissions in the North China Plain.

Land use change could profoundly influence the terrestrial ecosystem carbon (C) cycle. However, the effects of agricultural expansion and cropland abandonment on soil microbial respiration remain controversial, and the underlying mechanisms of the land use change effect are lacking. In this study, we conducted a comprehensive survey in four land use types (grassland, cropland, orchard, and old-field grassland) of North China Plain with eight replicates to explore the responses of soil microbial respiration to agricultural expansion and cropland abandonment. We collected surface soil (0-10 cm in depth) in each land use type to measure soil physicochemical property and microbial analysis. Our results showed that soil microbial respiration was significantly increased by 15.10 mg CO2 kg-1 day-1 and 20.06 mg CO2 kg-1 day-1 due to the conversion of grassland to cropland and orchard, respectively. It confirmed that agricultural expansion might exacerbate soil C emissions. On the contrary, the returning of cropland and orchard to old-field grassland significantly decreased soil microbial respiration by 16.51 mg CO2 kg-1 day-1 and 21.47 mg CO2 kg-1 day-1, respectively. Effects of land use change on soil microbial respiration were predominately determined by soil organic and inorganic nitrogen contents, implying that nitrogen fertilizer plays an essential role in soil C loss. These findings highlight that cropland abandonment can effectively mitigate soil CO2 emissions, which should be implemented in agricultural lands with low grain production and high C emissions. Our results improve mechanistic understanding on the response of soil C emission to land use changes.

Bioactive compounds from Huashi Baidu decoction possess both antiviral and anti-inflammatory effects against COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health concern, and effective antiviral reagents are urgently needed. Traditional Chinese medicine theory-driven natural drug research and development (TCMT-NDRD) is a feasible method to address this issue as the traditional Chinese medicine formulae have been shown effective in the treatment of COVID-19. Huashi Baidu decoction (Q-14) is a clinically approved formula for COVID-19 therapy with antiviral and anti-inflammatory effects. Here, an integrative pharmacological strategy was applied to identify the antiviral and anti-inflammatory bioactive compounds from Q-14. Overall, a total of 343 chemical compounds were initially characterized, and 60 prototype compounds in Q-14 were subsequently traced in plasma using ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. Among the 60 compounds, six compounds (magnolol, glycyrrhisoflavone, licoisoflavone A, emodin, echinatin, and quercetin) were identified showing a dose-dependent inhibition effect on the SARS-CoV-2 infection, including two inhibitors (echinatin and quercetin) of the main protease (Mpro), as well as two inhibitors (glycyrrhisoflavone and licoisoflavone A) of the RNA-dependent RNA polymerase (RdRp). Meanwhile, three anti-inflammatory components, including licochalcone B, echinatin, and glycyrrhisoflavone, were identified in a SARS-CoV-2-infected inflammatory cell model. In addition, glycyrrhisoflavone and licoisoflavone A also displayed strong inhibitory activities against cAMP-specific 3',5'-cyclic phosphodiesterase 4 (PDE4). Crystal structures of PDE4 in complex with glycyrrhisoflavone or licoisoflavone A were determined at resolutions of 1.54 Å and 1.65 Å, respectively, and both compounds bind in the active site of PDE4 with similar interactions. These findings will greatly stimulate the study of TCMT-NDRD against COVID-19.

SARS-CoV-2 Z-RNA activates the ZBP1-RIPK3 pathway to promote virus-induced inflammatory responses.

SARS-CoV-2 infection can trigger strong inflammatory responses and cause severe lung damage in COVID-19 patients with critical illness. However, the molecular mechanisms by which the infection induces excessive inflammatory responses are not fully understood. Here, we report that SARS-CoV-2 infection results in the formation of viral Z-RNA in the cytoplasm of infected cells and thereby activates the ZBP1-RIPK3 pathway. Pharmacological inhibition of RIPK3 by GSK872 or genetic deletion of MLKL reduced SARS-CoV-2-induced IL-1ß release. ZBP1 or RIPK3 deficiency leads to reduced production of both inflammatory cytokines and chemokines during SARS-CoV-2 infection both in vitro and in vivo. Furthermore, deletion of ZBP1 or RIPK3 alleviated SARS-CoV-2 infection-induced immune cell infiltration and lung damage in infected mouse models. These results suggest that the ZBP1-RIPK3 pathway plays a critical role in SARS-CoV-2-induced inflammatory responses and lung damage. Our study provides novel insights into how SARS-CoV-2 infection triggers inflammatory responses and lung pathology, and implicates the therapeutic potential of targeting ZBP1-RIPK3 axis in treating COVID-19.

Preparation of copper-based catalysts from electroplating sludge by ultrasound treatment and their antibiotic degradation performance.

The recovery of heavy metals from electroplating sludge is important for alleviating heavy metal pollution and recycling metal resources. However, the selective recovery of metal resources is limited by the complexity of electroplating sludge. Herein, CuFe bimetallic Fenton-like catalysts were successfully prepared from electroplating sludge by a facile room-temperature ultrasonic-assisted co-precipitation method. The prepared CuFe-S mainly consisted of nanorods with diameters of 20-30 nm and lengths of 100-200 nm and a small number of irregular particles. Subsequently, we performed tetracycline (TC) degradation experiments, and the results showed that the product CuFe-S had very good performance over a wide pH range (2-11). At an initial pH = 2, CuFe-S could degrade 91.9% of 50 mg L-1 TC aqueous solution within 30 min, which is better than that of a single metal catalyst. Free radical scavenging experiments and electron paramagnetic resonance (EPR) tests revealed that ·OH was the main active species for the degradation of TC by CuFe-S. In conclusion, a CuFe bimetallic Fenton-like catalyst was developed for the catalytic degradation of antibiotics, which provides a novel technical route for the resource utilization of electroplating sludge and shows an important practical application prospect.

Short-term but not long-term perennial mugwort cropping increases soil organic carbon in Northern China Plain.

Perennial cropping has been an alternative land use type due to its widely accepted role in increasing soil carbon sequestration. However, how soil organic carbon (SOC) changes and its underlying mechanisms under different cropping years are still elusive. A chronosequence (0-, 3-, 6-, 20-year) of perennial mugwort cropping was chosen to explore the SOC dynamics and the underlying mechanisms in agricultural soils of Northern China Plain. The results revealed that SOC first increased and then decreased along the 20-year chronosequence. The similar patterns were also found in soil properties (including soil ammonium nitrogen, total nitrogen and phosphorus) and two C-degrading hydrolytic enzyme activities (i.e., α-glucosidase and ß-glucosidase). The path analysis demonstrated that soil ammonium nitrogen, total nitrogen, and plant biomass affected SOC primarily through the indirect impacts on soil pH, total phosphorus availability, and C-degrading hydrolytic enzyme activities. In addition, the contributions of soil properties are greater than those of biotic factors (plant biomass) to changes in SOC across the four mugwort cropping years. Nevertheless, the biotic factors may play more important roles in regulating SOC than abiotic factors in the long run. Moreover, SOC reached its maximum and was equaled to that under the conventional rotation when cropping mugwort for 7.44 and 14.88 years, respectively, which has critical implications for sustainable C sequestration of agricultural soils in Northern China Plain. Our observations suggest that short-term but not long-term perennial mugwort cropping is an alternative practice benefiting soil C sequestration and achieving the Carbon Neutrality goal in China.

Development of a Humanized VHH Based Recombinant Antibody Targeting Claudin 18.2 Positive Cancers.

Claudin 18.2 (CLDN18.2), a tight junction (TJ) family protein controlling molecule exchange between cells, is frequently over-expressed in gastric cancer, pancreatic adenocarcinomas and in a fraction of non-small cell lung cancer cases. The tumor properties indicate that CLDN18.2 could be an attractive drug target for gastric and pancreatic cancers. In this study, we present effective strategies for developing anti-CLDN18.2 therapeutic candidates, based on variable domain of heavy chain of heavy chain antibodies (VHHs). CLDN18.2-specific VHHs were isolated by panning a phage display library from an alpaca immunized with a stable cell line highly expressing CLDN18.2. Humanized VHHs fused with human IgG1 Fc, as potential therapeutic candidates, exhibited desirable binding specificity and affinity to CLDN18.2. In vitro experiments showed that hu7v3-Fc was capable of eliciting both antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) on CLDN18.2 positive tumor cells. In the mouse xenograft model, the anti-tumor efficacy of hu7v3-Fc was significantly more potent than Zolbetuximab, the benchmark anti-CLDN18.2 monoclonal antibody. Moreover, in vivo biodistribution using zirconium-89 (89Zr) labeled antibodies demonstrated that hu7v3-Fc (89Zr-hu7v3-Fc) exhibited a better tumor penetration and a faster tumor uptake than Zolbetuximab (89Zr-Zolbetuximab), which might be attributed to its smaller size and higher affinity. Taken together, anti-CDLN18.2 hu7v3-Fc is a promising therapeutic agent for human CLDN18.2 positive cancers. Furthermore, hu7v3 has emerged as a potential module for novel CLDN18.2 related therapeutics.

Contrasting Effects of Nitrogen Addition on Vegetative Phenology in Dry and Wet Years in a Temperate Steppe on the Mongolian Plateau.

Changes in spring and autumn phenology and thus growing season length (GSL) pose great challenges in accurately predicting terrestrial primary productivity. However, how spring and autumn phenology in response to land-use change and nitrogen deposition and underlying mechanisms remain unclear. This study was conducted to explore the GSL and its components [i.e., the beginning of growing season and ending of growing season (EGS)] in response to mowing and nitrogen addition in a temperate steppe on the Mongolia Plateau during 2 years with hydrologically contrasting condition [dry (2014) vs. wet (2015)]. Our results demonstrated that mowing advanced the BGS only by 3.83 days, while nitrogen addition advanced and delayed the BGS and EGS by 2.85 and 3.31 days, respectively, and thus prolonged the GSL by 6.16 days across the two growing seasons from 2014 to 2015. When analyzed by each year, nitrogen addition lengthened the GSL in the dry year (2014), whereas it shortened the GSL in the wet year (2015). Further analyses revealed that the contrasting impacts of nitrogen on the GSL were attributed to monthly precipitation regimes and plant growth rate indicated by the maximum of normalized difference vegetation index (NDVmax). Moreover, changes in the GSL and its two components had divergent impacts on community productivity. The findings highlight the critical role of precipitation regimes in regulating the responses of spring and autumn phenology to nutrient enrichment and suggest that the relationships of ecosystem productivity with spring and autumn phenology largely depend on interannual precipitation fluctuations under future increased nitrogen deposition scenarios.

A Portable Sign Language Collection and Translation Platform with Smart Watches Using a BLSTM-Based Multi-Feature Framework.

Continuous sign language recognition (CSLR) using different types of sensors to precisely recognize sign language in real time is a very challenging but important research direction in sensor technology. Many previous methods are vision-based, with computationally intensive algorithms to process a large number of image/video frames possibly contaminated with noises, which can result in a large translation delay. On the other hand, gesture-based CSLR relying on hand movement data captured on wearable devices may require less computation resources and translation time. Thus, it is more efficient to provide instant translation during real-world communication. However, the insufficient amount of information provided by the wearable sensors often affect the overall performance of this system. To tackle this issue, we propose a bidirectional long short-term memory (BLSTM)-based multi-feature framework for conducting gesture-based CSLR precisely with two smart watches. In this framework, multiple sets of input features are extracted from the collected gesture data to provide a diverse spectrum of valuable information to the underlying BLSTM model for CSLR. To demonstrate the effectiveness of the proposed framework, we test it on an extremely challenging and radically new dataset of Hong Kong sign language (HKSL), in which hand movement data are collected from 6 individual signers for 50 different sentences. The experimental results reveal that the proposed framework attains a much lower word error rate compared with other existing machine learning or deep learning approaches for gesture-based CSLR. Based on this framework, we further propose a portable sign language collection and translation platform, which can simplify the procedure of collecting gesture-based sign language dataset and recognize sign language through smart watch data in real time, in order to break the communication barrier for the sign language users.

Conical holographic display to expand the vertical field of view.

Recently, cylindrical holographic display technology as a 360-degree display technology has attracted much attention. However, all the studies are based on the field of view (FOV) in the azimuth direction, and the issue of FOV in the vertical direction has never been discussed. In this paper, a new holographic display is proposed to expand the vertical FOV by a conical holographic diffraction model, in which the object plane is the outer cylinder and the observation plane is a part of the cone. In this proposed method, the proposed diffraction model is firstly established by the Rayleigh-Sommerfeld diffraction formula, and then the convolution and FFT are used for a fast diffraction calculation. The correctness and effectiveness of our proposed method are verified by the simulation of Young's interference and the numerical reconstructions from the complex amplitude and encoded holograms, respectively. In addition, an accurate relationship between the conical inclination angle and the vertical FOV expansion is analyzed, and the simulation results show that our proposed method can significantly expand the vertical FOV by 0.4 of the original object. Therefore, the issue of the vertical FOV in cylindrical holography is deeply discussed and successfully addressed for the first time.

Large field-of-view holographic display by gapless splicing of multisegment cylindrical holograms.

A holographic three-dimensional (3D) display is a recognized and ideal 3D display technology. In the field of holographic research, cylindrical holography with the merit of 360° field of view (FOV) has recently become a hot issue, as it naturally solves the problem of limited FOV in planar holography. The recently proposed approximate phase compensation (APC) method successfully obtains larger FOV and fast generation of segment cylindrical hologram (SCH) in the visible light band. However, the FOV of SCH remains limited due to its intrinsic limitations, and, to our best knowledge, the issue has not been effectively addressed. In this paper, the restricted conditions are first analyzed for the generation of SCH by the APC method. Then, an FOV expansion method is proposed for realizing a large FOV holographic display by gapless splicing of multi-SCH. The proposed method can successfully obtain larger FOV cylindrical holograms and effectively eliminate the splicing gaps; its effectiveness is verified by the results of numerical simulation and optical experiments. Therefore, the proposed method can effectively solve the FOV limitation problem of the APC method for the generation of SCH in the visible band, realize a large FOV 3D display, and provide a useful reference for holographic 3D display.

A novel approach of fabricating monodispersed spherical MoSiBTiC particles for additive manufacturing.

It is very challenging to fabricate spherical refractory material powders for additive manufacturing (AM) because of their high melting points and complex compositions. In this study, a novel technique, freeze-dry pulsated orifice ejection method (FD-POEM), was developed to fabricate spherical MoSiBTiC particles without a melting process. Elemental nanopowders were dispersed in water to prepare a high-concentration slurry, which was subsequently extruded from an orifice by diaphragm vibration and frozen instantly in liquid nitrogen. After a freeze-drying process, spherical composite particles with arbitrary composition ratios were obtained. The FD-POEM particles had a narrow size range and uniform elemental distribution. Mesh structures were formed within the FD-POEM particles, which was attributed to the sublimation of ice crystals. Furthermore, owing to their spherical morphology, the FD-POEM particles had a low avalanche angle of 42.6°, exhibiting good flowability. Consequently, the combination of FD-POEM and additive manufacturing has great potential for developing complex refractory components used in industrial applications.

Full-Length Transcriptome Analysis Reveals Candidate Genes Involved in Terpenoid Biosynthesis in Artemisia argyi.

Artemisia argyi is an important medicinal plant widely utilized for moxibustion heat therapy in China. The terpenoid biosynthesis process in A. argyi is speculated to play a key role in conferring its medicinal value. However, the molecular mechanism underlying terpenoid biosynthesis remains unclear, in part because the reference genome of A. argyi is unavailable. Moreover, the full-length transcriptome of A. argyi has not yet been sequenced. Therefore, in this study, de novo transcriptome sequencing of A. argyi's root, stem, and leaf tissues was performed to obtain those candidate genes related to terpenoid biosynthesis, by combining the PacBio single-molecule real-time (SMRT) and Illumina sequencing NGS platforms. And more than 55.4 Gb of sequencing data and 108,846 full-length reads (non-chimeric) were generated by the Illumina and PacBio platform, respectively. Then, 53,043 consensus isoforms were clustered and used to represent 36,820 non-redundant transcripts, of which 34,839 (94.62%) were annotated in public databases. In the comparison sets of leaves vs roots, and leaves vs stems, 13,850 (7,566 up-regulated, 6,284 down-regulated) and 9,502 (5,284 up-regulated, 4,218 down-regulated) differentially expressed transcripts (DETs) were obtained, respectively. Specifically, the expression profile and KEGG functional enrichment analysis of these DETs indicated that they were significantly enriched in the biosynthesis of amino acids, carotenoids, diterpenoids and flavonoids, as well as the metabolism processes of glycine, serine and threonine. Moreover, multiple genes encoding significant enzymes or transcription factors related to diterpenoid biosynthesis were highly expressed in the A. argyi leaves. Additionally, several transcription factor families, such as RLK-Pelle_LRR-L-1 and RLK-Pelle_DLSV, were also identified. In conclusion, this study offers a valuable resource for transcriptome information, and provides a functional genomic foundation for further research on molecular mechanisms underlying the medicinal use of A. argyi leaves.

Liquid-Phase Assisted Engineering of Highly Strong SiC Composite Reinforced by Multiwalled Carbon Nanotubes.

Despite the ultrahigh intrinsic strength of multiwalled carbon nanotube (MWCNT), the strengthening effect on ceramic matrix composite remains far from expectation mainly due to the weak load transfer between the reinforcement and ceramic matrix. With the assistance of the in situ pullout test, it is revealed that the liquid-phase sintering (LPS) can serve as a novel strategy to achieve effective load transfer in MWCNT reinforced ceramic matrix composites. The YAlO3 formed liquid phase during spark plasma sintering of SiC composite greatly facilitates radical elastic deformation of MWCNT, leading to highly increased interfacial shear strength (IFSS) as well as interlayer shear resistance (ISR) of nested walls. The liquid phase with superior wettability can even penetrate into the defects of MWCNT, which further increases the ISR of MWCNT. Moreover, the first-principles calculation indicates that the oxygen terminated YAlO3 phase displays much stronger bonding compared with SiC matrix, which is also responsible for the large IFSS in the composite. As a result, as high as 30% improvement of bending strength is achieved in the composite with only 3 wt% MWCNT in comparison to the monolithic ceramic, manifesting the unprecedented strengthening effect of MWCNT assisted by LPS.

A global database of plant production and carbon exchange from global change manipulative experiments.

Numerous ecosystem manipulative experiments have been conducted since 1970/80 s to elucidate responses of terrestrial carbon cycling to the changing atmospheric composition (CO2 enrichment and nitrogen deposition) and climate (warming and changing precipitation regimes), which is crucial for model projection and mitigation of future global change effects. Here, we extract data from 2,242 publications that report global change manipulative experiments and build a comprehensive global database with 5,213 pairs of samples for plant production (productivity, biomass, and litter mass) and ecosystem carbon exchange (gross and net ecosystem productivity as well as ecosystem and soil respiration). Information on climate characteristics and vegetation types of experimental sites as well as experimental facilities and manipulation magnitudes subjected to manipulative experiments are also included in this database. This global database can facilitate the estimation of response and sensitivity of key terrestrial carbon-cycling variables under future global change scenarios, and improve the robust projection of global change‒terrestrial carbon feedbacks imposed by Earth System Models.

[Effects of berberine on learning and memory ability in vascular cognitive impairment rats].

OBJECTIVE: To investigate the effects of berberine on learning and memory ability in vascular cognitive impairment rats. METHODS: Sixty-eight Wistar rats were randomly divided into control group (n=10), sham operated group (n=10) and the modeling group of vascular cognitive impairment rat (n=48), then the rats in modeling group were randomly divided into four groups (n=10): vehicle group, berberine low dose group (20 mg/kg), medium dose group (40 mg/kg) and high dose group (60 mg/kg). Bilateral common carotid arteries were occluded in rats to establish vascular cognitive impairment (VCI) model. Different doses of berberine were intraperitoneally injected into the treatment group and normal saline was intraperitoneally injected into the other groups once a day for a total of 34 days. After 28 days of administration, Morris water maze was used to test the learning and memory ability of rats. After the water maze experiment, the levels of superoxide dismutase (SOD) activity, glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor alpha(TNF-α), interleukin-1 beta (IL-1ß), 5-hydroxytryptamine (5-HT) and monoamine oxidase (MAO) in the forebrain cortex were detected. RESULTS: Compared to sham group, the escape latency in VCI group was significantly extended (P＜0.01) and the times of passing through the platform were decreased remarkably (P＜0.01). The levels of SOD, GSH and 5-HT in the hippocampus or anterior cortex were decreased significantly (P＜0.01), while the contents of MDA, TNF-α, IL-1ß and MAO were increased remarkably (P＜0.01). Compared with VCI group, the escape latency in berberine-treated groups was shortened significantly (P＜0.01, P＜0.05) and the times of passing through the platform were increased remarkably (P＜0.01, P＜0.05), the levels of SOD, GSH and 5-HT were increased significantly (P＜0.01), while the contents of TNF-α, IL-1ß and MAO were decreased remarkably (P＜0.01). CONCLUSION: Berberine could significantly improve the spatial learning and memory abilities of rats with vascular cognitive impairment. The mechanism may be related to the effects of berberine on the hippocampal antioxidant stress, anti-inflammatory response and the monoamine neurotransmitter system in the forebrain cortex. Berberine 60 mg/kg dose group had better effect.

Asymmetric responses of plant community structure and composition to precipitation variabilities in a semi-arid steppe.

Changing precipitation regimes can profoundly affect plant growth in terrestrial ecosystems, especially in arid and semi-arid regions. However, how changing precipitation, especially extreme precipitation events, alters plant diversity and community composition is still poorly understood. A 3-year field manipulative experiment with seven precipitation treatments, including - 60%, - 40%, - 20%, 0% (as a control), + 20%, + 40%, and + 60% of ambient growing-season precipitation, was conducted in a semi-arid steppe in the Mongolian Plateau. Results showed total plant community cover and forb cover were enhanced with increased precipitation and reduced under decreased precipitation, whereas grass cover was suppressed under the - 60% treatment only. Plant community and grass species richness were reduced by the - 60% treatment only. Moreover, our results demonstrated that total plant community cover was more sensitive to decreased than increased precipitation under normal and extreme precipitation change, and species richness was more sensitive to decreased than increased precipitation under extreme precipitation change. The community composition and low field water holding capacity may drive this asymmetric response. Accumulated changes in community cover may eventually lead to changes in species richness. However, compared to control, Shannon-Weiner index (H) did not respond to any precipitation treatment, and Pielou's evenness index (E) was reduced under the + 60% treatment across the 3 year, but not in each year. Thus, the findings suggest that plant biodiversity in the semi-arid steppe may have a strong resistance to precipitation pattern changes through adjusting its composition in a short term.

A meta-analysis of 1,119 manipulative experiments on terrestrial carbon-cycling responses to global change.

Direct quantification of terrestrial biosphere responses to global change is crucial for projections of future climate change in Earth system models. Here, we synthesized ecosystem carbon-cycling data from 1,119 experiments performed over the past four decades concerning changes in temperature, precipitation, CO2 and nitrogen across major terrestrial vegetation types of the world. Most experiments manipulated single rather than multiple global change drivers in temperate ecosystems of the USA, Europe and China. The magnitudes of warming and elevated CO2 treatments were consistent with the ranges of future projections, whereas those of precipitation changes and nitrogen inputs often exceeded the projected ranges. Increases in global change drivers consistently accelerated, but decreased precipitation slowed down carbon-cycle processes. Nonlinear (including synergistic and antagonistic) effects among global change drivers were rare. Belowground carbon allocation responded negatively to increased precipitation and nitrogen addition and positively to decreased precipitation and elevated CO2. The sensitivities of carbon variables to multiple global change drivers depended on the background climate and ecosystem condition, suggesting that Earth system models should be evaluated using site-specific conditions for best uses of this large dataset. Together, this synthesis underscores an urgent need to explore the interactions among multiple global change drivers in underrepresented regions such as semi-arid ecosystems, forests in the tropics and subtropics, and Arctic tundra when forecasting future terrestrial carbon-climate feedback.