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.

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.

Seasonal and vertical patterns of water availability and variability determine plant reproductive phenology.

BACKGROUND AND AIMS: Changing precipitation regimes can influence terrestrial plants and ecosystems. However, plant phenological responses to changing precipitation temporal patterns and the underlying mechanisms are largely unclear. This study was conducted to explore the effects of seasonal precipitation redistribution on plant reproductive phenology in a temperate steppe. METHODS: A field experiment with control (C), advanced (AP) and delayed (DP) growing-season precipitation peaks, and the combination of AP and DP (ADP) were employed. Seven dominant plant species were selected and divided into two functional groups (early- vs. middle-flowering species, shallow- vs. deep-rooted species) to monitor reproductive phenology including budding, flowering, and fruiting date, as well as reproductive duration for four growing seasons from 2015 to 2017, and 2022. KEY RESULTS: The AP, but not DP treatment advanced the phenological (i.e., budding, flowering, and fruiting) dates and lengthened the reproductive duration across the 4 growing seasons and 7 monitored species. In addition, the phenological responses showed divergent patterns among different plant functional groups, which could be attributed to shifts in soil moisture and its variability in different months and soil depths. Moreover, species with lengthened reproductive duration increased phenological overlap with other species, which could have a negative impact on their dominance under the AP treatment. CONCLUSIONS: Our findings reveal that changing precipitation seasonality could have considerable impacts on plant phenology by affecting soil water availability and variability. Incorporating these two factors simultaneously in the phenology models will help us understand the response of plant phenology under intensified changing precipitation scenarios. In addition, the observations of decreased dominance for the species with lengthened reproductive duration suggest that changing reproductive phenology can have a potential to affect community composition in grasslands under global change.

COVID-19 in the Tibet, China, the roof of the world: a comparative analysis of high-altitude residents and newcomers.

BACKGROUND: After a 920-day hiatus, COVID-19 resurged in the Tibet Autonomous Region of China in August 2022. This study compares the characteristics of COVID-19 between high-altitude residents and newcomers, as well as between newcomers and lowlanders. METHODS: This multi-center cohort study conducted at the Third People's Hospital of Tibet Autonomous Region and Beijing University Shenzhen Hospital, included 520 high-altitude resident patients, 53 high-altitude newcomer patients, and 265 lowlander patients infected with the Omicron variant. Initially, we documented epidemiological, clinical, and treatment data across varying residency at admission. We compared the severity of COVID-19 and various laboratory indicators, including hemoglobin concentration and SpO2%, over a 14-day period from the date of the first positive nucleic acid test, as well as the differences in treatment methods and disease outcomes between highlanders and high-altitude newcomers. We also compared several characteristics of COVID-19 between high-altitude newcomers and lowlanders. Univariate analysis, multivariable logistic regression, and the generalized linear mixed model were utilized for the analysis. RESULTS: No fatalities were observed. The study found no significant differences in COVID-19 severity or in the physiological measures of hemoglobin concentration and SpO2% between high-altitude and lowland residents. Similarly, there were no statistically significant differences in the values or trends of hemoglobin and SpO2% between high-altitude residents and newcomers throughout the 14-day observation period. However, compared to age- and sex-matched lowlander patients (1:5 ratio), high-altitude newcomers exhibited higher heart rates, respiratory rates, and average hemoglobin concentrations, along with lower platelet counts. There were no significant differences in hospital stays between the two groups. CONCLUSIONS: High-altitude residents and newcomer patients exhibit clinical similarities. However, the clinical characteristics of high-altitude newcomers and lowlander patients differ due to the impact of the high-altitude environment. These results highlight potential considerations for public health strategies in high-altitude regions such as Tibet.

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.

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.

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.

Elevated CO2 does not stimulate carbon sink in a semi-arid grassland.

Elevated CO2 is widely accepted to enhance terrestrial carbon sink, especially in arid and semi-arid regions. However, great uncertainties exist for the CO2 fertilisation effects, particularly when its interactions with other global change factors are considered. A four-factor (CO2 , temperature, precipitation and nitrogen) experiment revealed that elevated CO2 did not affect either gross ecosystem productivity or ecosystem respiration, and consequently resulted in no changes of net ecosystem productivity in a semi-arid grassland despite whether temperature, precipitation and nitrogen were elevated or not. The observations could be primarily attributable to the offset of ecosystem carbon uptake by enhanced soil carbon release under CO2 enrichment. Our findings indicate that arid and semi-arid ecosystems may not be sensitive to CO2 enrichment as previously expected and highlight the urgent need to incorporate this mechanism into most IPCC carbon-cycle models for convincing projection of terrestrial carbon sink and its feedback to climate change.

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.

Relationship Between the Serum Total Bilirubin and Inflammation in Patients With Psoriasis Vulgaris.

BACKGROUND: Psoriasis is a chronic and recurrent inflammatory skin disease. Previous studies have shown that bilirubin has anti-inflammation and antioxidant effects. However, the various roles of bilirubin in psoriasis patients are still unclear. OBJECTIVE: To investigate the serum total bilirubin (TB) level in the individuals with psoriasis vulgaris and further evaluate the relationship between serum TB concentration and C-reactive protein (CRP) to clarify the effect of bilirubin on inflammation. METHODS: A total of 214 patients with psoriasis vulgaris and 165 age- and gender-matched healthy control subjects were recruited. The peripheral leukocyte count (white blood cell, WBC) and differential, serum biochemical and immunologic indexes including serum TB, immunoglobulin (Ig) G, IgA, IgM, complement C3 and C4 , as well as serum CRP concentrations were measured. RESULTS: Results showed that the serum TB level decreased significantly and peripheral WBC, neutrophil, and serum CRP concentrations increased significantly in patients with psoriasis vulgaris. Meanwhile, the serum CRP was negatively correlated with serum TB levels but positively correlated with peripheral WBC and the Psoriasis Area and Severity Index (PASI). Logistic regression analysis showed that the serum TB was a protective factor for psoriasis vulgaris. CONCLUSION: The present study suggests that lower serum TB is associated with the enhancement of the inflammatory response in psoriasis vulgaris. Therefore, lower serum TB has a prognostic significance for worsening psoriasis vulgaris. Bilirubin may play a crucial role in inflammation by contributing to the inhibition of the inflammatory response.

[Progress on clinical application of bevacizumab for the treatment of refractory cervical cancer].

Bevacizumab is increasingly used in recurrent, persistent or metastatic cervical cancer. The early retrospective case reports found that bevacizumab combined with 5-FU (including capecitabine) or paclitaxel was well tolerated and displayed encouraging anti-tumor activity in recurrent or persistent cervical cancer. Phase Ⅱ clinical trials showed that bevacizumab was well tolerated and active in the second- and third-line treatment of patients with recurrent cervical cancer. Large scale phase Ⅱ and phase Ⅲ clinical trials demonstrated that bevacizumab-containing chemotherapy was effective in the first- and second-line treatment of patients with persistent cervical cancer, prolonged survival time and improved remission rate. The article also reviews the research progress on predictive factors of bevacizumab efficacy, showing the use of imaging and biomarkers in predicting the efficacy of bevacizumab treatment. In addition, this article analyzes the cost-effectiveness of bevacizumab, finding that bevacizumab combined with chemotherapy meets the standard of cost-effectiveness.

Genome mining-directed activation of a silent angucycline biosynthetic gene cluster in Streptomyces chattanoogensis.

Genomic sequencing of actinomycetes has revealed the presence of numerous gene clusters seemingly capable of natural product biosynthesis, yet most clusters are cryptic under laboratory conditions. Bioinformatics analysis of the completely sequenced genome of Streptomyces chattanoogensis L10 (CGMCC 2644) revealed a silent angucycline biosynthetic gene cluster. The overexpression of a pathway-specific activator gene under the constitutive ermE* promoter successfully triggered the expression of the angucycline biosynthetic genes. Two novel members of the angucycline antibiotic family, chattamycins A and B, were further isolated and elucidated. Biological activity assays demonstrated that chattamycin B possesses good antitumor activities against human cancer cell lines and moderate antibacterial activities. The results presented here provide a feasible method to activate silent angucycline biosynthetic gene clusters to discover potential new drug leads.

Transcriptome-guided identification of SprA as a pleiotropic regulator in Streptomyces chattanoogensis.

Quorum sensing molecular γ-butyrolactones (GBL) are widely distributed among the genus Streptomyces. Their cognate receptors have been demonstrated to control secondary metabolism and/or morphological differentiation. ScgA is responsible for the biosynthesis of GBL in Streptomyces chattanoogensis. According to the genome-wide transcriptome analysis of the ΔscgA mutant, we found that the expression of sprA, which encodes a GBL receptor homologue, was shown to be positively regulated by ScgA. Electrophoretic mobility shift assays and DNase I footprinting assays showed that SprA bound to two specific autoregulatory element (ARE) sequences located upstream of the sprA gene, indicating that its expression is self-regulated. SprA was involved in biosynthesis of GBL by repressing the expression of scgA. An Escherichia coli-based luciferase report system demonstrated that SprA directly repressed the expression of scgR, which encodes a GBL receptor. Like deletion of scgA, the disruption of sprA resulted in decreased production of the antibiotic natamycin in liquid culture and retarded morphological differentiation on solid agar. This work indicates that SprA acts as a pleiotropic regulator of both morphogenesis and the production of natamycin.

Sigma factor WhiGch positively regulates natamycin production in Streptomyces chattanoogensis L10.

The roles of many sigma factors are unclear in regulatory mechanism of secondary metabolism in Streptomyces. Here, we report the regulation network of a group 3 sigma factor, WhiGch, from a natamycin industrial strain Streptomyces chattanoogensis L10. WhiGch regulates the growth and morphological differentiation of S. chattanoogensis L10. The whiG ch deletion mutant decreased natamycin production by about 30 % and delayed natamycin production more than 24 h by delaying the growth. Overexpression of the whiG ch gene increased natamycin production in large scale production medium by about 26 %. WhiGch upregulated the transcription of natamycin biosynthetic gene cluster and inhibited the expression of migrastatin and jadomycin analog biosynthetic polyketide synthase genes. WhiGch positively regulated natamycin biosynthetic gene cluster by directly binding to the promoters of scnC and scnD, which were involved in natamycin biosynthesis, and these binding sites adjacent to translation start codon were determined. Thus, this paper further elucidates the high natamycin yield mechanisms of industrial strains and demonstrates that a valuable improvement in the yield of the target metabolites can be achieved through manipulating the transcription regulators.

WblAch, a pivotal activator of natamycin biosynthesis and morphological differentiation in Streptomyces chattanoogensis L10, is positively regulated by AdpAch.

Detailed mechanisms of WhiB-like (Wbl) proteins involved in antibiotic biosynthesis and morphological differentiation are poorly understood. Here, we characterize the role of WblAch, a Streptomyces chattanoogensis L10 protein belonging to this superfamily. Based on DNA microarray data and verified by real-time quantitative PCR (qRT-PCR), the expression of wblAch was shown to be positively regulated by AdpAch. Gel retardation assays and DNase I footprinting experiments showed that AdpAch has specific DNA-binding activity for the promoter region of wblAch. Gene disruption and genetic complementation revealed that WblAch acts in a positive manner to regulate natamycin production. When wblAch was overexpressed in the wild-type strain, the natamycin yield was increased by ∼30%. This provides a strategy to generate improved strains for natamycin production. Moreover, transcriptional analysis showed that the expression levels of whi genes (including whiA, whiB, whiH, and whiI) were severely depressed in the ΔwblAch mutant, suggesting that WblAch plays a part in morphological differentiation by influencing the expression of the whi genes.

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.

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.

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.

Costly punishment does not always increase cooperation.

In a pairwise interaction, an individual who uses costly punishment must pay a cost in order that the opponent incurs a cost. It has been argued that individuals will behave more cooperatively if they know that their opponent has the option of using costly punishment. We examined this hypothesis by conducting two repeated two-player Prisoner's Dilemma experiments, that differed in their payoffs associated to cooperation, with university students from Beijing as participants. In these experiments, the level of cooperation either stayed the same or actually decreased when compared with the control experiments in which costly punishment was not an option. We argue that this result is likely due to differences in cultural attitudes to cooperation and punishment based on similar experiments with university students from Boston that found cooperation did increase with costly punishment.