Metabolomics analysis of rice fermented by medicinal fungi providing insights into the preparation of functional food.

Rice, a primary staple food, may be improved in value via fermentation. Here, ten medicinal basidiomycetous fungi were separately applied for rice fermentation. After preliminary screening, Ganoderma boninense, Phylloporia pulla, Sanghuangporus sanghuang and Sanghuangporus weigelae were selected for further LC-MS based determination of the changes in metabolic profile after their fermentation with rice, and a total of 261, 296, 312, and 355 differential compounds were identified, respectively. Most of these compounds were up-regulated and involved in the metabolic pathways of amino acid metabolism, lipid metabolism, carbohydrate metabolism and the biosynthesis of other secondary metabolites. Sanghuangporus weigelae endowed the rice with the highest nutritional and bioactive values. The metabolic network of the identified differential compounds in rice fermented by S. weigelae illustrated their close relationships. In summary, this study provides insights into the preparation and application of potential functional food via the fermentation of rice with medicinal fungi.

Characterization of solid waste deposit using electrical resistivity tomography and time domain induced polarization.

The whopping increase in solid waste landfills poses serious threats to the environment. Compared to the drilling method, geophysical methods are effective, non-invasive techniques for delineating the contaminant distribution. In this study, electrical resistivity tomography (ERT) and induced polarization (IP) were used to investigate a solid waste deposit. The results of ERT/IP imaging illustrate the potential of the method in environmental studies. Based on the results of 21 survey lines, geo-electrical signals can be summarized as three types: with only high resistivity for construction & demolition wastes (CDWs) areas (RO type), contaminated soil for high chargeability (CO type), and contaminants under CDWs layer have both high resistivity and chargeability (RC type). Chargeability values over 10.2 mV/V correspond to contaminated soil with an overall concentration larger than 75 mg/kg. With the three-dimensional interpolation results and the determined chargeability criteria, the total volume of contaminated soil is 40,555 cubic meters. Finally, comparing the efficiency, cost and results of IP and drilling sampling methods shows that the IP is an efficient, low-cost and high-resolution contamination characterization. The results support that ERT/IP information can fulfill rapid and initial identification as a reliable tool in engineering and environmental investigations.

The shifting pattern of CO2 source sink in a subtropical urbanizing lightly eutrophic lake.

Globally, numerous freshwater lakes exist, and rapid urbanization has impacted carbon biogeochemical cycling at the interface where water meets air in these bodies. However, there is still a limited understanding of CO2 absorption/emission in eutrophic urbanizing lakes. This study therefore involved biweekly in-situ monitoring to evaluate fluctuations in the partial pressure (pCO2) and flux (fCO2) of CO2 and associated parameters from January to September 2020 (7:00-17:00 CST) in an urbanizing lake in southwestern China. Our study revealed that during the daylight hours of the 11 sampling days, both pCO2 and fCO2 consistently demonstrated decreasing trends from the early morning period to the late afternoon period, with notable increases on May 7th and August 15th, respectively. Interestingly, unlike our previous findings, an nonsignificant difference (p > 0.05) in mean pCO2 and fCO2 was observed between the morning period and the afternoon period (n = 22). Furthermore, the mean pCO2 in January (~105 µatm; n = 4) and April (133-212 µatm; n = 8) was below the typical atmospheric CO2 level (C-sink), while that in the other months surpassed 410 µatm (C-source), although the average values (n = 44) of pCO2 and fCO2 were 960 ± 841 µatm and 57 ± 85 mmol m-2 h-1, respectively. Moreover, the pCO2 concentration was significantly greater in summer (May to August, locally reaching 1087 µatm) than in spring (January to April at 112 µatm), indicating a seasonal shift between the C-sink (spring) and the C-source (summer). In addition, a significant positive correlation in pCO2/fCO2 with chlorophyll-a/nitrate but a negative correlation in dissolved oxygen and total phosphorus were recorded, suggesting that photosynthesis and respiration were identified as the main drivers of CO2 absorption/emissions, while changes in nitrate and phosphorus may be attributed to urbanization. Overall, our investigations indicated that this lightly eutrophic lake demonstrated a distinct shifting pattern of CO2 source-sink variability at daily and seasonal scales.

Prognostic significance of PET/CT and its association with immuno-genomic profiling in oesophageal squamous cell carcinoma treated with immunotherapy plus chemoradiotherapy: results from a phase II study.

BACKGROUND: A phase II trial (EC-CRT-001) demonstrated the promising efficacy of combining toripalimab (an anti-PD-1 antibody) with definitive chemoradiotherapy (CRT) for locally advanced oesophageal squamous cell carcinoma (ESCC). Biomarkers are key to identifying patients who may benefit from this therapeutic approach. METHODS: Of the 42 patients with ESCC who received toripalimab combined with definitive CRT, 37 were included in this analysis. Baseline assessments included PET/CT metabolic parameters (SUVmax, SUVmean, SUVpeak, MTV, and TLG), RNA sequencing of tumour biopsies to quantify the tissue mutational burden (TMB), and multiplex immunofluorescence staining to estimate immune cell infiltration in the tumour microenvironment (TME). Frozen neoplastic samples were procured for RNA sequencing to further explore the immune-related TME. RESULTS: Among the 37 patients, high baseline SUVmax (≥12.0; OR = 6.5, 95% CI 1.4-48.2, p = 0.032) and TLG (≥121.8; OR = 6.8, 95% CI 1.6-33.5, p = 0.012) were significantly correlated with lower complete response rates. All five PET/CT parameters were notably associated with overall survival; only SUVmax and TLG were associated with a significantly worse progression-free survival. A trend towards an inverse correlation was observed between SUVmax and TMB (R = -0.33, p = 0.062). PD-1 + CD8 + T cell infiltration was negatively correlated with MTV (R = -0.355, p = 0.034) and TLG (R = -0.385, p = 0.021). Moreover, RNA sequencing revealed that the high TLG subgroup exhibited low immune cell infiltration, indicating an immunosuppressive landscape. CONCLUSIONS: High baseline SUVmax and TLG might predict poorer treatment response and worse survival in patients with ESCC undergoing immunotherapy combined with CRT. In addition, high PET/CT metabolic parameters, particularly TLG, were correlated with an immunosuppressive TME, which warrants further exploration.

Erratum: miR-181a, delivered by hypoxic PTC-secreted exosomes, inhibits DACT2 by downregulating MLL3, leading to YAP-VEGF-mediated angiogenesis.

[This corrects the article DOI: 10.1016/j.omtn.2021.02.027.].

Comparison of Efficacy and Safety of Combined Chemoimmunotherapy With or Without Radiation Therapy for Stage IVB Esophageal Squamous Cell Carcinoma: A Multicenter Propensity Score Matching Analysis.

PURPOSE: This study aimed to compare the efficacy and safety of combining first-line chemoimmunotherapy with radiation therapy versus chemoimmunotherapy alone in patients with stage IVB esophageal squamous cell carcinoma (ESCC). METHODS AND MATERIALS: We retrospectively examined 409 patients with stage IVB ESCC who received first-line chemotherapy and anti-PD-1 antibody, with or without radiation therapy of ≥40 Gy radiation dose to primary lesion, from 4 academic cancer centers between October 2018 and December 2022. Propensity score matching was conducted to minimize the potential confounding effects. RESULTS: In the overall cohort of 409 patients, the group that received additional radiation therapy had superior overall survival (OS) (hazard ratio [HR], 0.51; 95% CI, 0.39-0.66; P < .001) and progression-free survival (PFS) (HR, 0.52; 95% CI, 0.40-0.66; P < .001) compared to the group that received chemoimmunotherapy alone. After 1:1 propensity score matching, matching age, tumor location, and metastatic sites, a total of 250 patients were selected for further analysis. The results remained consistent and showed that the addition of radiation therapy significantly improved OS and PFS (median OS, 24.9 vs 14.6 months; P = .003; median PFS, 14.2 vs 10.6 months; P = .002). Multivariate Cox analysis including tumor location, T stage, metastatic sites, and treatment modality, revealed that radiation therapy was an independent prognostic factor for both OS (HR, 0.57; 95% CI, 0.41-0.81) and PFS (HR, 0.63, 95% CI, 0.47-0.86). Subgroup analyses revealed significant OS prolongation in patients with nonregional lymph node metastases only who received radiation therapy (HR, 0.49; 95% CI, 0.34-0.70). No OS survival benefit was observed in those with distant organ metastases (HR, 0.72; 95% CI, 0.46-1.13). Regarding safety, the group receiving additional radiation therapy had higher incidences of grade 3 to 4 lymphopenia (74.4% vs 17.7%, P < .001) and esophagitis (11.2% vs 2.4%, P = .006). CONCLUSIONS: The addition of radiation therapy to chemoimmunotherapy improved the survival of stage IVB ESCC patients with nonregional lymph node metastasis.

Predictive role of ctDNA in esophageal squamous cell carcinoma receiving definitive chemoradiotherapy combined with toripalimab.

The combination of toripalimab (an anti-PD-1 antibody) with definitive chemoradiotherapy (CRT) demonstrated encouraging efficacy against locally advanced esophageal squamous cell carcinoma (ESCC) in the EC-CRT-001 phase II trial (NCT04005170). The primary endpoint of this trial was the clinical complete response rate (cCR), and the secondary endpoints included overall survival (OS), progression-free survival (PFS), duration of response, and quality of life. The exploratory analyses of EC-CRT-001 include exploring the role of circulating tumor DNA (ctDNA) and blood-based tumor mutational burden (bTMB) in predicting the response and survival. In total, 118 blood and 35 tissue samples from 42 enrolled patients were included in the analyses. We found that ctDNA-negative patients achieved a higher cCR compared to those with detectable ctDNA during CRT (83%, 19/23 vs. 39%, 7/18; p = 0.008) or post-CRT (78%, 21/27 vs. 30%, 3/10; p = 0.017). Patients with detectable ctDNA during CRT had shorter PFS (p = 0.014). Similarly, patients with post-CRT detectable ctDNA had a significantly shorter PFS (p = 0.012) and worse OS (p = 0.004). Moreover, patients with high bTMB levels during CRT had prolonged OS (p = 0.027). In conclusion, ctDNA and bTMB have the potential to predict treatment efficacy and survival in ESCC treated with CRT and immunotherapy.

Multi-objective ecological restoration priority in China: Cost-benefit optimization in different ecological performance regimes based on planetary boundaries.

In the context of the "United Nations Decade on Ecosystem Restoration", optimizing spatiotemporal arrangements for ecological restoration is an important approach to enhancing overall socioecological benefits for sustainable development. However, against the background of ecological degradation caused by the human use of most natural resources at levels that have approached or exceeded the safe and sustainable boundaries of ecosystems, it is key to explain how to optimize ecological restoration by classified management and optimal total benefits. In response to these issues, we combined spatial heterogeneity and temporal dynamics at the national scale in China to construct five ecological performance regimes defined by indicators that use planetary boundaries and ecological pressures which served as the basis for prioritizing ecological restoration areas and implementing zoning control. By integrating habitat conservation, biodiversity, water supply, and restoration cost constraints, seven ecological restoration scenarios were simulated to optimize the spatial layout of ecological restoration projects (ERPs). The results indicated that the provinces with unsustainable freshwater use, climate change, and land use accounted for more than 25%, 66.7%, and 25%, respectively, of the total area. Only 30% of the provinces experienced a decrease in environmental pressure. Based on the ecological performance regimes, ERP sites spanning the past 20 years were identified, and more than 50% of the priority areas were clustered in regime areas with increased ecological stress. As the restoration area targets doubled (40%) from the baseline (20%), a multi-objective scenario presents a trade-off between expanded ERPs in areas with highly beneficial effects and minimal restoration costs. In conclusion, a reasonable classification and management regime is the basis for targeted restoration. Coordinating multiple objectives and costs in ecological restoration is the key to maximizing socio-ecological benefits. Our study offered new perspectives on systematic and sustainable planning for ecological restoration.

A commercial humic acid inhibits benzo(a)pyrene biodegradation by Paracoccus aminovorans HPD-2.

Benzo(a)pyrene (BaP) is posing serious threats to soil ecosystems and its bioremediation usually limited by environmental factors and microbial activity. Humic acid (HA), a ubiquitous heterogeneous organic matter, which could affect the fate of environmental pollutants. However, the impact of HA on bioremediation of organic contamination remains controversial. In the present study, the biodegradation of BaP by Paracoccus aminovorans HPD-2 with and without HA was explored. Approximately 87.4 % of BaP was biodegraded in the HPD-2 treatment after 5 days of incubation, whereas the addition of HA dramatically reduced BaP biodegradation to 56.0 %. The limited BaP biodegradation in the HA + HPD-2 treatment was probably due to the decrease of BaP bioavailability which induced by the adsorption of HA with unspecific interactions. The excitation-emission matrix (EEM) of fluorescence characteristics showed that strain HPD-2 was responsible for the presence of protein-like substances and the microbial original humic substances in the HPD-2 treatment. Addition of HA would result in the increase of soluble microbial humic-like material, which should ascribe to the biodegradation of BaP and probably utilization of HA. Furthermore, both the growth and survival of strain HPD-2 were inhibited in the HA + HPD-2 treatment, because of the limited available carbon source (i.e. BaP) at the presence of HA. The expression of gene1789 and gene2589 dramatically decreased in the HA + HPD-2 treatment, and this should be responsible for the decrease of BaP biodegradation as well. This study reveals the mechanism that HA affect the BaP biodegradation, and the decrease of biodegradation should ascribe to the interaction of HA and bacterial strain. Thus, the bioremediation strategies of PAHs need to consider the effects of organic matter in environment.

Gastroschisis prevalence patterns in 27 surveillance programs from 24 countries, International Clearinghouse for Birth Defects Surveillance and Research, 1980-2017.

BACKGROUND: Gastroschisis is a serious birth defect with midgut prolapse into the amniotic cavity. The objectives of this study were to evaluate the prevalence and time trends of gastroschisis among programs in the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), focusing on regional variations and maternal age changes in the population. METHODS: We analyzed data on births from 1980 to 2017 from 27 ICBDSR member programs, representing 24 countries and three regions (Europe+ (includes Iran) , Latin America, North America). Cases were identified using diagnostic codes (i.e., 756.7, 756.71, or Q79.3). We excluded cases of amniotic band syndrome, limb-body wall defect, and ruptured omphalocele. Programs provided annual counts for gastroschisis cases (live births, stillbirths, and legally permitted pregnancy terminations for fetal anomalies) and source population (live births, stillbirths), by maternal age. RESULTS: Overall, gastroschisis occurred in 1 of every 3268 births (3.06 per 10,000 births; 95% confidence intervals [CI]: 3.01, 3.11), with marked regional variation. European+ prevalence was 1.49 (95%CI: 1.44, 1.55), Latin American 3.80 (95%CI: 3.69, 3.92) and North American 4.32 (95%CI: 4.22, 4.42). A statistically significant increasing time trend was observed among six European+ , four Latin American, and four North American programs. Women <20 years of age had the highest prevalence in all programs except the Slovak Republic. CONCLUSIONS: Gastroschisis prevalence increased over time in 61% of participating programs, and the highest increase in prevalence was observed among the youngest women. Additional inquiry will help to assess the impact of the changing maternal age proportions in the birth population on gastroschisis prevalence.

The clinical performance and population health impact of birthweight-for-gestational age indices at term gestation.

BACKGROUND: The assessment of birthweight for gestational age and the identification of small- and large-for-gestational age (SGA and LGA) infants remain contentious, despite the recent creation of the Intergrowth 21st Project and World Health Organisation (WHO) birthweight-for-gestational age standards. OBJECTIVE: We carried out a study to identify birthweight-for-gestational age cut-offs, and corresponding population-based, Intergrowth 21st and WHO centiles associated with higher risks of adverse neonatal outcomes, and to evaluate their ability to predict serious neonatal morbidity and neonatal mortality (SNMM) at term gestation. METHODS: The study population was based on non-anomalous, singleton live births between 37 and 41 weeks' gestation in the United States from 2003 to 2017. SNMM included 5-min Apgar score <4, neonatal seizures, need for assisted ventilation, and neonatal death. Birthweight-specific SNMM was modelled by gestational week using penalised B-splines. The birthweights at which SNMM odds were minimised (and higher by 10%, 50% and 100%) were estimated, and the corresponding population, Intergrowth 21st, and WHO centiles were identified. The clinical performance and population impact of these cut-offs for predicting SNMM were evaluated. RESULTS: The study included 40,179,663 live births and 991,486 SNMM cases. Among female singletons at 39 weeks' gestation, SNMM odds was lowest at 3203 g birthweight, and 10% higher at 2835 g and 3685 g (population centiles 11th and 82nd, Intergrowth centiles 17th and 88th and WHO centiles 15th and 85th). Birthweight cut-offs were poor predictors of SNMM, for example, the cut-offs associated with 10% and 50% higher odds of SNMM among female singletons at 39 weeks' gestation resulted in a sensitivity, specificity, and population attributable fraction of 12.5%, 89.4%, and 2.1%, and 2.9%, 98.4% and 1.3%, respectively. CONCLUSIONS: Reference- and standard-based birthweight-for-gestational age indices and centiles perform poorly for predicting adverse neonatal outcomes in individual infants, and their associated population impact is also small.

Preliminary species diversity and community phylogenetics of wood-inhabiting basidiomycetous fungi in the Dabie Mountains, Central China reveal unexpected richness.

Wood-inhabiting fungi have important economic values as well as playing a major ecological role in forest ecosystem cycles. The Dabie Mountains, at the junction of Henan, Hubei, and Anhui Provinces, Central China, provide an ideal climate and favorable niches for the speciation and diversification of various forms of life including fungi. We studied the species diversity and community phylogenetics of wood-inhabiting basidiomycetous fungi that revealed 175 wood-inhabiting basidiomycetous species, of which 20 represented unidentified species, based on morphological and phylogenetic analyses of 575 specimens collected from ten sampling sites. These species belonged to two classes, 11 orders, 42 families, and 106 genera of Basidiomycota, and included 12 edible species, 28 medicinal species, four poisonous species, and seven forest pathogens. Four types of fungal distribution pattern at the genus level were recognized for 65 genera, while another 41 genera could not be placed in any known distribution pattern. The five sampling sites in the eastern part of the Dabie Mountains had significantly higher species diversity and phylogenetic diversity of wood-inhabiting basidiomycetous fungi than those in the western part, and thus deserve priority in terms of conservation. The community of wood-inhabiting basidiomycetous fungi in the Dabie Mountains is generally affected by a combination of habitat filtering and competitive exclusion. This study provides a basis on which to build actions for the comprehensive recognition, utilization, and conservation of wood-inhabiting basidiomycetous fungi in the region.

Pooled rates and demographics of POTS following SARS-CoV-2 infection versus COVID-19 vaccination: Systematic review and meta-analysis.

PURPOSE: To address recent concerns of postural orthostatic tachycardia syndrome (POTS) occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination. METHODS: We searched PubMed, Web of Science, and Scopus as of 1st June 2023. We performed a systematic review and meta-analysis of pooled POTS rate in SARS-CoV-2-infected and COVID-19-vaccinated groups from epidemiological studies, followed by subgroup analyses by characteristic. Meta-analysis of risk ratio was conducted to compare POTS rate in infected versus uninfected groups. Meta-analysis of demographics was also performed to compare cases of post-infection and post-vaccination POTS from case reports and series. RESULTS: We estimated the pooled POTS rate of 107.75 (95 % CI: 9.73 to 273.52) and 3.94 (95 % CI: 0 to 16.39) cases per 10,000 (i.e., 1.08 % and 0.039 %) in infected and vaccinated individuals based on 5 and 2 studies, respectively. Meta-regression revealed age as a significant variable influencing 86.2 % variance of the pooled POTS rate in infected population (P < 0.05). Moreover, POTS was 2.12-fold more likely to occur in infected than uninfected individuals (RR = 2.12, 95 % CI: 1.71 to 2.62, P < 0.001). Meta-analyzed demographics for cases of post-infection (n = 43) and post-vaccination (n = 17) POTS found no significant differences in several variables between groups, except that the time from exposure to symptom onset was shorter for cases of post-vaccination POTS (P < 0.05). CONCLUSION: Although evidence is limited for post-vaccination POTS, our study showed that POTS occur more frequently following SARS-CoV-2 infection than COVID-19 vaccination.

How to synergize ecological restoration to co-benefit the beneficial contributions of nature to people on the Qinghai-Tibet Plateau?

Understanding the magnitude and spatial distribution of ecological restoration requires a precise assessment of the beneficial contributions of nature to people. However, where the restoration areas should be located and whether the natural contribution of a compensation area can satisfy people's needs in the context of ecological degradation remain unclear. To address these issues, we selected the Qinghai-Tibet Plateau as the study areas, utilizing the offset portfolio analyzer and locator model to identify the compensation sites that offset the losses of ecosystem services and biodiversity resulting from ecological degradation. These compensation sites were developed through two offset types: restoration and protection. Then, based on the offset sites, we assessed nature's contribution to people (NCP) under the current status and future scenarios in terms of various aspects, including the habitat (NCP1), climate change (NCP4), and water quantity and flow regulation (NCP6). This study found that the area impacted by agricultural development was 7.15 × 105 ha, and the required compensation area was 5.5 × 106 ha under the current status. The ratio of the impacted area to the required area was approximately 7.0 in the future scenarios. The average habitat qualities were 0.14 and 0.30, while the mean NCP1 values were 2.69 and 0.51 in the protection and restoration offset sites, respectively. Moreover, based on the offset sites, the high-value contributions in NCP4 accounted for 18.64%-22.69% and 38.87%-46.17% of the total offset sites in terms of the restoration and protection offset types, respectively. Additionally, the estimated high-value contributions in NCP6 accounted for 58.35%-59.02% and 84.40%-95.86% of the total offset sites in the restoration and protection offset types, respectively. Our findings highlighted the significance of ecological restoration in showcasing the role of NCPs. These results could aid conservation managers in developing more targeted ecological strategies to enhance human well-being.

A novel immune-related prognostic signature based on Chemoradiotherapy sensitivity predicts long-term survival in patients with esophageal squamous cell carcinoma.

Background: There is a heterogenous clinical response following chemoradiotherapy (CRT) in esophageal squamous cell carcinoma (ESCC). Therefore, we aimed to study signaling pathway genes that affect CRT sensitivity and prognosis. Methods: Gene expression analyses were performed in the GEO and TCGA datasets. A immunohistochemistry (IHC) analysis was performed in pretreatment biopsies. Results: MMP13 was found to be highly expressed in the "Pathologic Complete Response (pCR)" and "Complete Remission (CR)" and "Alive" groups. Th17 cells and MMP9/13 showed a negative correlation in immune infiltration analysis. In GSEA analysis, IL-4 and IL-13 signaling pathways were highly enriched in patients exhibiting high MMP expression in pCR and CR groups. IHC results suggested higher MMP13 & IL-4 and lower IL-17A & RORC expression in the CR group compared to the 0.70, and the model could well distinguish high-risk and low-risk subgroups. Conclusion: The above results may provide guidance for developing novel treatment and prognostic strategies in ESCC patients.

A phase II clinical trial of toripalimab combined with neoadjuvant chemoradiotherapy in locally advanced esophageal squamous cell carcinoma (NEOCRTEC1901).

Background: To evaluate the efficacy and safety of toripalimab combined with neoadjuvant chemoradiotherapy (NCRT) for locally advanced esophageal squamous cell carcinoma (ESCC). Methods: In this single arm, phase II trial, 44 ESCC patients were enrolled from December 2019 to July 2021 at Sun Yat-sen University Cancer Center (Guangzhou, China). All patients received concurrent radiotherapy (44 Gy in 20 fractions), chemotherapy (paclitaxel 50 mg/m2 and cisplatin 25 mg/m2 on days 1, 8, 15, and 22), and toripalimab (240 mg on days 1 and 22). Within 6-8 weeks of neoadjuvant treatment, patients underwent surgery. The results of the study patients were compared with those of 86 matched patients between July 2015 and March 2022. The primary endpoint was pathological complete response (pCR) rate, and the secondary endpoints were treatment-related adverse events and R0 rates. This trail was registered with ClinicalTrails.gov, NCT04006041. Findings: All patients received neoadjuvant treatment, and 42 completed esophagectomy. Of the 42 patients, 21 (50%; 95% CI 35-65) achieved pCR and 2 (5%) patients were ypT0N+. The R0 resection rate was 98% (41/42). Nine (20%) of 44 patients had grade 3/4 adverse events. Among the perioperative complications (n = 42), anastomotic leakage occurred in five cases (12%), tracheal fistula in three cases (7%), and postoperative death in one case (2%) due to tracheal fistula. Compared with the control cohort, the pCR rate of the study group was higher but without significant difference (50% vs. 36%, P = 0.19). Interpretation: Toripalimab combined with NCRT failed to show significantly better pCR rate than historical data. Nevertheless, considering the signs of efficacy and acceptable safety of this regimen, further evaluation in phase III randomized trials might be warranted. Funding: National Natural Science Foundation of China.

Xenasmatellales ord. nov. and Xenasmatellaceae fam. nov. for Xenasmatella (Agaricomycetes, Basidiomycota).

In the era of molecular phylogeny as dominant evidence in fungal taxonomy, the taxonomic framework of fungi adopted from morphological characteristics has been largely updated. Compared with other fungal groups, macrofungi underwent fewer updates at the order and higher level. In this study, the taxonomic placement of a poorly known macro-basidiomycetous genus Xenasmatella is studied. Phylogenetic and molecular clock analyses inferred from a seven-locus dataset support that the genus represents an order rank lineage. Accordingly, a monotypic order Xenasmatellales and a monotypic family Xenasmatellaceae are newly introduced for Xenasmatella within Agaricomycetes. The species diversity and relationships of Xenasmatella are further clarified with the aid of the phylogenetic analysis inferred from a four-locus dataset. In association with morphological characteristics, a new species Xenasmatella hjortstamii is described. Moreover, the distribution of Xenasmatella ailaoshanensis, X. gossypina, and X. wuliangshanensis previously known only from type localities in Yunnan Province, China are expanded. In addition, two unnamed single-specimen lineages of Xenasmatella from Victoria State, Australia and Sichuan, China are revealed, likely representing two potential new species of this genus. In summary, the current study updates the taxonomic framework of Agaricomycetes and provides a crucial supplement for comprehensively understanding the evolutionary history of this fungal class.

Scientific concept and practices of life community of mountains, rivers, forests, farmlands, lakes, grasslands, and deserts in China.

China prioritizes ecological civilization construction and embraces the concept of "lucid waters and lush mountains are invaluable assets." Great achievements have been made in ecological protection and restoration through implementing a series of policies and projects. This paper reviews the history of ecological restoration in China and the current development of the "integrated protection and restoration project of mountains, rivers, forests, farmlands, lakes, grasslands, and deserts (IPRP)." Furthermore, the characteristics of IPRP were systematically elaborated from the perspectives of the ecological civilization thought, the policy management, and the key scientific issues. Also, the current achievements were summarized in the fields of national ecological space management, biodiversity conservation, and ecological protection and restoration. Existing challenges in management policy, scientific issues, and engineering practices were highlighted. Future perspectives include ecological space control, nature-based Solutions, biodiversity big data platform, modern techniques, and value realization mechanisms of ecological products.

Resilience assessment of the nitrogen flow system in food production and consumption for sustainable development on the Qinghai-Tibet Plateau.

A robust and resilient nitrogen (N) flow system can effectively ensure consistent food production and consumption activities while preserving environmental quality. In this study, we constructed an indicator system to evaluate N flow system resilience including food production and consumption, at the county scale on the Qinghai-Tibet Plateau (QTP) from 1998 to 2018. The subsystem coupling coordination degree (CCD) and the effect of N losses on N flow system resilience were subsequently explored. The results indicated that despite the overall N flow system resilience remaining low and exhibiting spatiotemporal disparities from 1998 to 2018, over 90 % of the counties experienced improvements. High resilience areas (>0.15) were mainly concentrated in some counties in Sichuan Province, where N losses were positively correlated with system resilience. The level of resilience depended on agricultural and livestock development, and the CCD of subsystems was also high (>0.5) in this region, with the most balanced environmental and socioeconomic development. The low system resilience areas were concentrated in the eastern part of the QTP, where human activities caused substantial disturbances. The fragmentation of the agro-pastoral system coupled with the low system resilience of the food production and driving pressure subsystems led to low CCD between subsystems. In contrast, the western regions, characterized by a stable food production system, high food self-sufficiency, and weak dependence on external systems, showed a higher degree of system resilience and resistance. Our findings provide a reference for N resource management and policy formulation for food production and consumption in the agricultural and pastoral areas of the QTP.