An orchestrated ethylene-gibberellin signaling cascade contributes to mesocotyl elongation and emergence of rice direct seeding.

A mechanized direct seeding of rice with less labor and water usage, has been widely adopted. However, this approach requires varieties that exhibit uniform seedling emergence. Mesocotyl elongation (ME) offers the main drive of fast emergence of rice seedlings from soils; nevertheless, its genetic basis remains unknown. Here, we identify a major rice quantitative trait locus Mesocotyl Elongation1 (qME1), an allele of the Green Revolution gene Semi-Dwarf1 (SD1), encoding GA20-oxidase for gibberellin (GA) biosynthesis. ME1 expression is strongly induced by soil depth and ethylene. When rice grains are direct-seeded in soils, the ethylene core signaling factor OsEIL1 directly promotes ME1 transcription, accelerating bioactive GA biosynthesis. The GAs further degrade the DELLA protein SLENDER RICE 1 (SLR1), alleviating its inhibition of rice PHYTOCHROME-INTERACTING FACTOR-LIKE13 (OsPIL13) to activate the downstream expansion gene OsEXPA4 and ultimately promote rice seedling ME and emergence. The ancient traits of long mesocotyl and strong emergence ability in wild rice and landrace were gradually lost in company with the Green Revolution dwarf breeding process, and an elite ME1-R allele (D349H) is found in some modern Geng varieties (long mesocotyl lengths) in northern China, which can be used in the direct seeding and dwarf breeding of Geng varieties. Furthermore, the ectopic and high expression of ME1 driven by mesocotyl-specific promoters resulted in rice plants that could be direct-seeded without obvious plant architecture or yield penalties. Collectively, we reveal the molecular mechanism of rice ME, and provide useful information for breeding new Green Revolution varieties with long mesocotyl suitable for direct-seeding practice.

OsLESV and OsESV1 promote transitory and storage starch biosynthesis to determine rice grain quality and yield.

Transitory starch is an important carbon source in leaves, and its biosynthesis and metabolism are closely related to grain quality and yield. The molecular mechanisms controlling leaf transitory starch biosynthesis and degradation and their effects on rice (Oryza sativa) quality and yield remain unclear. Here, we show that OsLESV and OsESV1, the rice orthologs of AtLESV and AtESV1, are associated with transitory starch biosynthesis in rice. The total starch and amylose contents in leaves and endosperms are significantly reduced, and the final grain quality and yield are compromised in oslesv and osesv1 single and oslesv esv1 double mutants. Furthermore, we found that OsLESV and OsESV1 bind to starch, and this binding depends on a highly conserved C-terminal tryptophan-rich region that acts as a starch-binding domain. Importantly, OsLESV and OsESV1 also interact with the key enzymes of starch biosynthesis, granule-bound starch synthase I (GBSSI), GBSSII, and pyruvate orthophosphote dikiase (PPDKB), to maintain their protein stability and activity. OsLESV and OsESV1 also facilitate the targeting of GBSSI and GBSSII from plastid stroma to starch granules. Overexpression of GBSSI, GBSSII, and PPDKB can partly rescue the phenotypic defects of the oslesv and osesv1 mutants. Thus, we demonstrate that OsLESV and OsESV1 play a key role in regulating the biosynthesis of both leaf transitory starch and endosperm storage starch in rice. These findings deepen our understanding of the molecular mechanisms underlying transitory starch biosynthesis in rice leaves and reveal how the transitory starch metabolism affects rice grain quality and yield, providing useful information for the genetic improvement of rice grain quality and yield.

G6PD maintains the VSMC synthetic phenotype and accelerates vascular neointimal hyperplasia by inhibiting the VDAC1-Bax-mediated mitochondrial apoptosis pathway.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) plays an important role in vascular smooth muscle cell (VSMC) phenotypic switching, which is an early pathogenic event in various vascular remodeling diseases (VRDs). However, the underlying mechanism is not fully understood. METHODS: An IP‒LC‒MS/MS assay was conducted to identify new binding partners of G6PD involved in the regulation of VSMC phenotypic switching under platelet-derived growth factor-BB (PDGF-BB) stimulation. Co-IP, GST pull-down, and immunofluorescence colocalization were employed to clarify the interaction between G6PD and voltage-dependent anion-selective channel protein 1 (VDAC1). The molecular mechanisms involved were elucidated by examining the interaction between VDAC1 and apoptosis-related biomarkers, as well as the oligomerization state of VDAC1. RESULTS: The G6PD level was significantly elevated and positively correlated with the synthetic characteristics of VSMCs induced by PDGF-BB. We identified VDAC1 as a novel G6PD-interacting molecule essential for apoptosis. Specifically, the G6PD-NTD region was found to predominantly contribute to this interaction. G6PD promotes VSMC survival and accelerates vascular neointimal hyperplasia by inhibiting VSMC apoptosis. Mechanistically, G6PD interacts with VDAC1 upon stimulation with PDGF-BB. By competing with Bax for VDAC1 binding, G6PD reduces VDAC1 oligomerization and counteracts VDAC1-Bax-mediated apoptosis, thereby accelerating neointimal hyperplasia. CONCLUSION: Our study showed that the G6PD-VDAC1-Bax axis is a vital switch in VSMC apoptosis and is essential for VSMC phenotypic switching and neointimal hyperplasia, providing mechanistic insight into early VRDs.

Alpha-fetoprotein predicts the treatment efficacy of immune checkpoint inhibitors for gastric cancer patients.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are commonly used in conjunction with chemotherapy to improve treatment outcomes for patients with gastric cancer. Since AFP could influence immunity by both inhibiting natural killer (NK) cells and regulating negatively the function of dendritic cells, we evaluated the influence of baseline serum alpha-fetoprotein (AFP) levels on the curative effect of ICIs in advanced gastric cancer (AGC) patients. METHODS: A retrospective analysis was conducted on 158 AGC patients who underwent ICI treatment. The patients were divided into high and low groups based on the AFP threshold of 20 ng/ml. The efficacy of ICI treatment was assessed using objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). RESULTS: The higher levels of baseline AFP were found to be associated with a decrease in the effectiveness of ICIs, as evidenced by a DCR of 50.0% in the group with high AFP levels compared to 87.7% in the group with low AFP levels (P < 0.001). Further analysis using Kaplan-Meier survival techniques indicated that a high AFP level was linked to shorter progression-free survival (PFS) (P < 0.001) and overall survival (OS) (P = 0.001) in AGC individuals receiving ICIs. After propensity score matching, a log rank test revealed that the high AFP group had a decrease in median PFS (P = 0.011) and median OS (P = 0.036) compared to the low AFP group. The high AFP levels also showed its association with shorter PFS and OS in the subgroup analysis of ICI plus chemotherapy patients. CONCLUSIONS: Baseline AFP levels may predict immune checkpoint inhibitor treatment efficacy in AGC patients.

OsLEA1b Modulates Starch Biosynthesis at High Temperatures in Rice.

High temperatures accelerate the accumulation of storage material in seeds, often leading to defects in grain filling. However, the mechanisms regulating grain filling at high temperatures remain unknown. Here, we want to explore the quality factors influenced by the environment and have identified a LATE EMBROYGENESIS ABUNDANT gene, OsLEA1b, a heat-stress-responsive gene in rice grain filling. OsLEA1b is highly expressed in the endosperm, and its coding protein localizes to the nucleus and cytoplasm. Knock-out mutants of OsLEA1b had abnormal compound starch granules in endosperm cells and chalky endosperm with significantly decreased grain weight and grain number per panicle. The oslea1b mutants exhibited a lower proportion of short starch chains with degrees of polymerization values from 6 to 13 and a higher proportion of chains with degrees from 14 to 48, as well as significantly lower contents of starch, protein, and lipid compared to the wild type. The difference was exacerbated under high temperature conditions. Moreover, OsLEA1b was induced by drought stress. The survival rate of oslea1b mutants decreased significantly under drought stress treatment, with significant increase in ROS levels. These results indicate that OsLEA1b regulates starch biosynthesis and influences rice grain quality, especially under high temperatures. This provides a valuable resource for genetic improvement in rice grain quality.

Geranylgeranylacetone Ameliorates Skin Inflammation by Regulating and Inducing Thioredoxin via the Thioredoxin Redox System.

Geranylgeranylacetone (GGA) exerts cytoprotective activity against various toxic stressors via the thioredoxin (TRX) redox system; however, its effect on skin inflammation and molecular mechanism on inducing the TRX of GGA is still unknown. We investigated the effects of GGA in a murine irritant contact dermatitis (ICD) model induced by croton oil. Both a topical application and oral administration of GGA induced TRX production and Nrf2 activation. GGA ameliorated ear swelling, neutrophil infiltration, and inhibited the expression of TNF-α, IL-1ß, GM-CSF, and 8-OHdG. GGA's cytoprotective effect was stronger orally than topically in mice. In vitro studies also showed that GGA suppressed the expression of NLRP3, TNF-α, IL-1ß, and GM-CSF and scavenged ROS in PAM212 cells after phorbol myristate acetate stimulation. Moreover, GGA induced endogenous TRX production and Nrf2 nuclear translocation in PAM212 cells (dependent on the presence of ROS) and activated the PI3K-Akt signaling pathway. GGA significantly downregulated thioredoxin-interacting protein (TXNIP) levels in PAM212 cells treated with or without Nrf2 siRNA. After knocking down Nrf2 in PAM212 cells, the effect of GGA on TRX induction was significantly inhibited. This suggests that GGA suppress ICD by inducing endogenous TRX, which may be regulated by PI3K/Akt/Nrf2 mediation of the TRX redox system.

The performance of the 2022 ACR/EULAR classification criteria for Takayasu's arteritis as compared to the 1990 ACR classification criteria in a Chinese population.

In this study, we studied the performance of the 2022 American College of Rheumatology (ACR)/ European Alliance of Associations for Rheumatology (EULAR) classification criteria for Takayasu's arteritis (TAK) as compared to the 1990 ACR classification criteria in a Chinese population. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and the area under the receiver operating characteristics curve (AUC) of the above two criteria were compared. The sensitivity (92.6%), positive predictive value (95.6%), negative predictive value (94.6%), accuracy (95.0%) and AUC (0.981) of the 2022 criteria were superior to those of the 1990 criteria (45.7%, 91.5%, 70.5%, 75.0% and 0.874, respectively), and the difference of AUC was statistically significant (Z = 5.362, P < 0.001). In addition, we included new imaging modalities in the 1990 criteria, whose sensitivity, positive predictive value, negative predictive value, accuracy and AUC were significantly improved, but still lower than those of the 2022 criteria, the difference in AUC was also statistically significant (Z = 2.023, P = 0.043). The 2022 criteria for TAK exhibited superior performance compared with the 1990 criteria and may be more appropriate for the Chinese population. Incorporating additional imaging modalities could enhance the classification performance of the 1990 criteria even further.

Superresolution structured illumination microscopy reconstruction algorithms: a review.

Structured illumination microscopy (SIM) has become the standard for next-generation wide-field microscopy, offering ultrahigh imaging speed, superresolution, a large field-of-view, and long-term imaging. Over the past decade, SIM hardware and software have flourished, leading to successful applications in various biological questions. However, unlocking the full potential of SIM system hardware requires the development of advanced reconstruction algorithms. Here, we introduce the basic theory of two SIM algorithms, namely, optical sectioning SIM (OS-SIM) and superresolution SIM (SR-SIM), and summarize their implementation modalities. We then provide a brief overview of existing OS-SIM processing algorithms and review the development of SR-SIM reconstruction algorithms, focusing primarily on 2D-SIM, 3D-SIM, and blind-SIM. To showcase the state-of-the-art development of SIM systems and assist users in selecting a commercial SIM system for a specific application, we compare the features of representative off-the-shelf SIM systems. Finally, we provide perspectives on the potential future developments of SIM.

Open-3DSIM: an open-source three-dimensional structured illumination microscopy reconstruction platform.

Open-3DSIM is an open-source reconstruction platform for three-dimensional structured illumination microscopy. We demonstrate its superior performance for artifact suppression and high-fidelity reconstruction relative to other algorithms on various specimens and over a range of signal-to-noise levels. Open-3DSIM also offers the capacity to extract dipole orientation, paving a new avenue for interpreting subcellular structures in six dimensions (xyzθλt). The platform is available as MATLAB code, a Fiji plugin and an Exe application to maximize user-friendliness.

Correlation between immune-related adverse events and treatment efficacy of anti-PD1 immunotherapy in patients with esophageal squamous cell carcinoma.

Immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) are associated with improved treatment efficacy in certain types of cancer. In the present study, we assessed the association between irAEs and ICI efficacy. Patients with esophageal squamous cell carcinoma (ESCC) who received ICI treatment were stratified into irAEs and non-irAE groups. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were used to evaluate the therapeutic efficacy of ICIs. Of the 78 ICI-treated ESCC patients, 39 developed irAEs. The median OS and PFS for all patients were 600 and 300 days, respectively. Median OS (P<0.001) and PFS (P<0.001) times of the patients with irAEs were longer than those in the non-irAE group. In addition, the DCR of the irAE group was higher than that of the non-irAE group (P=0.006). Univariate analysis indicated that the non-irAE group was associated with a relatively shorter OS [hazard ratio (HR)=3.687, 95% CI, 1.974-6.888, P<0.001] and PFS (HR=2.967, 95% CI, 1.691-5.204, P<0.001). The multifactorial analysis demonstrated that irAE status was an independent predictor of PFS (HR=3.564, 95% CI, 1.786-7.114, P<0.001) and OS (HR=3.288, 95% CI, 1.636-6.606, P=0.001). In conclusion, the present study demonstrated that irAEs could be used to predict improved treatment efficacy in patients with ESCC who received ICI therapy.

Phase-Dislocation-Mediated High-Dimensional Fractional Acoustic-Vortex Communication.

With unlimited topological modes in mathematics, the fractional orbital angular momentum (FOAM) demonstrates the potential to infinitely increase the channel capacity in acoustic-vortex (AV) communications. However, the accuracy and stability of FOAM recognition are still limited by the nonorthogonality and poor anti-interference of fractional AV beams. The popular machine learning, widely used in optics based on large datasets of images, does not work in acoustics because of the huge engineering of the 2-dimensional point-by-point measurement. Here, we report a strategy of phase-dislocation-mediated high-dimensional fractional AV communication based on pair-FOAM multiplexing, circular sparse sampling, and machine learning. The unique phase dislocation corresponding to the topological charge provides important physical guidance to recognize FOAMs and reduce sampling points from theory to practice. A straightforward convolutional neural network considering turbulence and misalignment is further constructed to achieve the stable and accurate communication without involving experimental data. We experimentally present that the 32-point dual-ring sampling can realize the 10-bit information transmission in a limited topological charge scope from ±0.6 to ±2.4 with the FOAM resolution of 0.2, which greatly reduce the divergence in AV communications. The infinitely expanded channel capacity is further verified by the improved FOAM resolution of 0.025. Compared with other milestone works, our strategy reaches 3-fold OAM utilization, 4-fold information level, and 5-fold OAM resolution. Because of the extra advantages of high dimension, high speed, and low divergence, this technology may shed light on the next-generation AV communication.

OPAQUE3, encoding a transmembrane bZIP transcription factor, regulates endosperm storage protein and starch biosynthesis in rice.

Starch and storage proteins are the main components of rice (Oryza sativa L.) grains. Despite their importance, the molecular regulatory mechanisms of storage protein and starch biosynthesis remain largely elusive. Here, we identified a rice opaque endosperm mutant, opaque3 (o3), that overaccumulates 57-kDa proglutelins and has significantly lower protein and starch contents than the wild type. The o3 mutant also has abnormal protein body structures and compound starch grains in its endosperm cells. OPAQUE3 (O3) encodes a transmembrane basic leucine zipper (bZIP) transcription factor (OsbZIP60) and is localized in the endoplasmic reticulum (ER) and the nucleus, but it is localized mostly in the nucleus under ER stress. We demonstrated that O3 could activate the expression of several starch synthesis-related genes (GBSSI, AGPL2, SBEI, and ISA2) and storage protein synthesis-related genes (OsGluA2, Prol14, and Glb1). O3 also plays an important role in protein processing and export in the ER by directly binding to the promoters and activating the expression of OsBIP1 and PDIL1-1, two major chaperones that assist with folding of immature secretory proteins in the ER of rice endosperm cells. High-temperature conditions aggravate ER stress and result in more abnormal grain development in o3 mutants. We also revealed that OsbZIP50 can assist O3 in response to ER stress, especially under high-temperature conditions. We thus demonstrate that O3 plays a central role in rice grain development by participating simultaneously in the regulation of storage protein and starch biosynthesis and the maintenance of ER homeostasis in endosperm cells.

Variations of nitrogen-metabolizing enzyme activity and microbial community under typical loading conditions in full-scale leachate anoxic/aerobic system.

Influent loading determines the performance of leachate treatment plant (LTP) facing the dynamic conditions, but enzyme expression in microbial community is unclear. Here, six nitrogen-metabolizing enzymes were detected during nitrification failures (NF), high loading (HL), low loading (LL), and low carbon/nitrogen (LCN) in a 500 m3/d LTP. Nitrogen removal in LL was 15 ± 5% higher than that in HL. The activity of hydroxylamine oxidoreductase decreased by 90% as the influent total nitrogen increased from 2450 mg/L to 3100 mg/L, which might be a critical enzyme causing the nitrification failure. Denitrifying enzyme abated by 1.3% as the carbon/nitrogen dropped by 1% in LCN. With the influent chemical oxygen demand decreased from 22000 mg/L to 12000 mg/L, the relative abundance of norank_f_Saprospiraceae dropped from 33.66% to 11.94%, and finally disappeared, which seems to be an indicator of the high load operation. These findings provide the basis for improving the efficiency of LTPs.

Molecular transformation and composition flow of dissolved organic matter in four typical concentrated leachates from the multi-stage membrane system.

Concentrated leachate (CL), characterized with high content salts and compositional complexity of dissolved organic matter (DOM), is difficult to degrade. Understanding the CL from molecular insight level is the requirement for further disposal based on their components. Here, typical CL samples were collected from the multi-stage membrane separation process in a large-scale leachate plant, including nanofiltration (NF), primary ultrafiltration (PUF), secondary nanofiltration (SNF), and reverse osmosis (RO). More than 95% of DOM was removed from raw CL, of which about 3/4 flowed into PUFCL and 1/5 flowed into SNFCL. DOM with macro-molecular weight (>500 Da, 30.46%) and highly unsaturated compounds (double-bond equivalents >15) were detected in PUFCL. Nearly half of DOM was CHO-only compounds (42.04%) in SNFCL. PUFCL was abundant in heteroatom species with higher-order oxygen (O ≥ 10), which was coincident with the trend of humic substance distribution (humic substance >1/2). Based on these properties results, advanced oxidation processes, such as ozonation, might be the right process for SNFCL rich in heteroatom species with low-order oxygen (O < 10). Abundant disulfides (S2O2-6 classes, 20.19%) and monovalent salts existed in ROCL, which should be removed from the system. These findings might provide basic information for the treatment of CLs from different membranes.

Decomposing the decoupling of plastics consumption and economic growth in G7 and China: Evidence from 2001 to 2020 based on China's import ban.

Plastic recycling is critical for dematerializing of plastics. It has a profound implication on decoupling economic growth from environmental pressure and advancing waste plastic governance domestically and internationally while identifying drivers that might improve decoupling. In this study, plastic consumption and recycling patterns are presented, and the factors influencing the acceleration of dematerialization subsequent to the ban were investigated in the G7 countries and China. The results show that plastic consumption increases from 7.60 million metric tons (mt) to 12.60 mt between 2017 and 2019, and subsequently rapidly decreases to 6.84 mt in 2020. The plastic recycling rate drastically decreased by 21.3% in 2017, and decreased slightly from 2017 to 2020, at an annual rate of 2.9% on average. China's ban shocked the decoupling trends, which showed resilience and motivated the development of robust plastic recycling, and the global recycling transformation pattern accelerated the dematerialization of plastics. Decoupling performances of the G7 and China gradually stabilized in 2019, and all the countries were strongly decoupled in 2020, although decoupling index (DI) fluctuates from 2017 to 2020. Among the recycling-trading drivers, the improvement of waste plastic quality in recycling contributes more to decoupling, the recycling rate shows a more negative decoupling effect on China before the ban, and the population effect is weak relative to other influencing factors. The factors revealed the mechanism of decoupling of plastic consumption in the recycling-trading process, and the recyclability improvement in terms of plastic quality is important for dematerialization.

CDE4 encodes a pentatricopeptide repeat protein involved in chloroplast RNA splicing and affects chloroplast development under low-temperature conditions in rice.

Pentatricopeptide repeat (PPR) proteins play important roles in the post-transcriptional modification of organellar RNAs in plants. However, the function of most PPR proteins remains unknown. Here, we characterized the rice (Oryza sativa L.) chlorophyll deficient 4 (cde4) mutant which exhibits an albino phenotype during early leaf development, with decreased chlorophyll contents and abnormal chloroplasts at low-temperature (20°C). Positional cloning revealed that CDE4 encodes a P-type PPR protein localized in chloroplasts. In the cde4 mutant, plastid-encoded polymerase (PEP)-dependent transcript levels were significantly reduced, but transcript levels of nuclear-encoded genes were increased compared to wild-type plants at 20°C. CDE4 directly binds to the transcripts of the chloroplast genes rpl2, ndhA, and ndhB. Intron splicing of these transcripts was defective in the cde4 mutant at 20°C, but was normal at 32°C. Moreover, CDE4 interacts with the guanylate kinase VIRESCENT 2 (V2); overexpression of V2 enhanced CDE4 protein stability, thereby rescuing the cde4 phenotype at 20°C. Our results suggest that CDE4 participates in plastid RNA splicing and plays an important role in rice chloroplast development under low-temperature conditions.

Investigation on the fast co-pyrolysis of sewage sludge with biomass and the combustion reactivity of residual char.

Gaining the valuable fuels from sewage sludge is a promising method. In this work, the fast pyrolysis characteristics of sewage sludge (SS), wheat straw (WS) and their mixtures in different proportions were carried out in a drop-tube reactor. The combustion reactivity of the residual char obtained was investigated in a thermogravimetric analyzer (TGA). Results indicate that SS and WS at different pyrolysis temperatures yielded different characteristic gas compositions and product distributions. The co-pyrolysis of SS with WS showed that there existed a synergistic effect in terms of higher gas and bio-oil yields and lower char yield, especially at the WS adding percentage of 80wt%. The addition of WS to SS increased the carbon content in the SS char and improved char porous structures, resulting in an improvement in the combustion reactivity of the SS char. The research results can be used to promote co-utilization of sewage sludge and biomass.