Summary
In rice (Oryza sativa L.), later flowering inferior spikelets (IS), which are located on proximal secondary branches, fill slowly and produce smaller and lighter grains than earlier flowering ...superior spikelets (SS). Many genes have been reported to be involved in poor grain filling of IS, however the underlying molecular mechanisms remain unclear. The present study determined that GF14f, a member of the 14‐3‐3 protein family, showed temporal and spatial differences in expression patterns between SS and IS. Using GF14f–RNAi plants, we observed that a reduction in GF14f expression in the endosperm resulted in a significant increase in both grain length and weight, which in turn improved grain yield. Furthermore, pull‐down assays indicated that GF14f interacts with enzymes that are involved in sucrose breakdown, starch synthesis, tricarboxylic acid (TCA) cycle and glycolysis. At the same time, an increase in the activity of sucrose synthase (SuSase), adenosine diphosphate‐glucose pyrophosphorylase (AGPase), and starch synthase (StSase) was observed in the GF14f–RNAi grains. Comprehensive analysis of the proteome and metabolite profiling revealed that the abundance of proteins related to the TCA cycle, and glycolysis increased in the GF14f–RNAi grains together with several carbohydrate intermediates. These results suggested that GF14f negatively affected grain development and filling, and the observed higher abundance of the GF14f protein in IS compared with SS may be responsible for poor IS grain filling. The study provides insights into the molecular mechanisms underlying poor grain filling of IS and suggests that GF14f could serve as a potential tool for improving rice grain filling.
Significance Statement
The 14‐3‐3 protein GF14f negatively affects grain filling of inferior spikelets and therefore may be useful in improving rice grain filling.
Summary
In rice (
Oryza sativa
L.), later flowering inferior spikelets (
IS
), which are located on proximal secondary branches, fill slowly and produce smaller and lighter grains than earlier ...flowering superior spikelets (
SS
). Many genes have been reported to be involved in poor grain filling of
IS
, however the underlying molecular mechanisms remain unclear. The present study determined that
GF
14f, a member of the 14‐3‐3 protein family, showed temporal and spatial differences in expression patterns between
SS
and
IS
. Using
GF
14f
–
RNA
i plants, we observed that a reduction in
GF
14f expression in the endosperm resulted in a significant increase in both grain length and weight, which in turn improved grain yield. Furthermore, pull‐down assays indicated that
GF
14f interacts with enzymes that are involved in sucrose breakdown, starch synthesis, tricarboxylic acid (
TCA
) cycle and glycolysis. At the same time, an increase in the activity of sucrose synthase (SuSase), adenosine diphosphate‐glucose pyrophosphorylase (
AGP
ase), and starch synthase (StSase) was observed in the
GF
14f
–
RNA
i grains. Comprehensive analysis of the proteome and metabolite profiling revealed that the abundance of proteins related to the
TCA
cycle, and glycolysis increased in the
GF
14f
–
RNA
i grains together with several carbohydrate intermediates. These results suggested that
GF
14f negatively affected grain development and filling, and the observed higher abundance of the
GF
14f protein in
IS
compared with
SS
may be responsible for poor
IS
grain filling. The study provides insights into the molecular mechanisms underlying poor grain filling of
IS
and suggests that
GF
14f could serve as a potential tool for improving rice grain filling.
Significance Statement
The 14‐3‐3 protein
GF
14f negatively affects grain filling of inferior spikelets and therefore may be useful in improving rice grain filling.
Post-translational modification by SUMO (small ubiquitin-like modifier) proteins has been shown to regulate a variety of functions of proteins, including protein stability, chromatin organization, ...transcription, DNA repair, subcellular localization, protein–protein interactions, and protein homeostasis. SENP (sentrin/SUMO-specific protease) regulates precursor processing and deconjugation of SUMO to control cellular mechanisms. SENP3, which is one of the SENP family members, deconjugates target proteins to alter protein modification. The effect of modification via SUMO and SENP3 is crucial to maintain the balance of SUMOylation and guarantee normal protein function and cellular activities. SENP3 acts as an oxidative stress-responsive molecule under physiological conditions. Under pathological conditions, if the SUMOylation process of proteins is affected by variations in SENP3 levels, it will cause a cellular reaction and ultimately lead to abnormal cellular activities and the occurrence and development of human diseases, including cardiovascular diseases, neurological diseases, and various cancers. In this review, we summarized the most recent advances concerning the critical roles of SENP3 in normal physiological and pathological conditions as well as the potential clinical implications in various diseases. Targeting SENP3 alone or in combination with current therapies might provide powerful targeted therapeutic strategies for the treatment of these diseases.
This article reports the time-dependent dielectric breakdown (TDDB) reliability of zirconia (ZrO2)-based MIM capacitors with sub-0.7-nm equivalent oxide thicknesses (EOT). Results indicate that ...substituting the top part of the ZrO2 with an Al2O3/ZrO2/Al2O3 (AZA) stack dramatically improves the reliability of the ultra-thin capacitors. The origin is attributed to Al-doping forming an amorphous crystalline phase; such phase lowers the average defect generation rate in the dielectric, which is crucial for slowing the formation of breakdown paths. As a result, the highest <inline-formula> <tex-math notation="LaTeX">{E} _{\mathbf {\textit {TDDB}}} </tex-math></inline-formula> of 4.18 MV/cm (0.01% failure rate @ 10 years) has been achieved in 5.0 nm ZrO2-AZA (ZAZA) devices (EOT = 0.63 nm). This work provides an effective approach to mitigate the reliability issues in ultra-thin dielectrics using fabrication technologies compatible with industrial applications.
Objective. The purpose of this study was to investigate the effect of targeted psychological intervention combined with standardized pain care on postoperative pain, depression, and anxiety in ...patients with intestinal obstruction. Methods. 84 patients with intestinal obstruction hospitalized at our hospital from October 2019 to February 2021 were randomly divided into study and control groups. The patients in the control group were treated with routine nursing, and the patients in the study group were treated with focused psychological intervention combined with standardized pain nursing. The pain degree (VAS), depression and anxiety (SDS, SAS) score, sleep quality (PSQI) score, and nursing satisfaction of the two groups before and after intervention were calculated. Results. Before intervention, no significant differences in VAS score between the study and control groups were observed. The VAS score of 6 h, 12 h, 24 h, and 48 h dry prognosis in the study group was lower than that in the control group. There was no significant difference in the scores of SDS and SAS between two groups. After intervention, the scores of SDS and SAS in the study group were lower than those in the control group. After intervention, the scores of daytime dysfunction, hypnotic drugs, sleep disorders, sleep efficiency, sleep time, and sleep quality in the study group were significantly lower than those in the control group. The scores of nursing state, nursing technique, nurse-patient communication, and inspection observation in the study group were higher than those in the control. Conclusion. The intervention of focused psychological intervention combined with standardized pain nursing on patients with intestinal obstruction can effectively relieve their negative emotion and reduce the degree of postoperative pain. In addition, it can improve patients’ sleep quality and enhance patients’ satisfaction with all kinds of nursing work.
The accurate prediction of the outcome of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is impeded by population heterogeneity. The study aimed to assess the impact of ...underlying cirrhosis on the performance of clinical prediction models (CPMs).
Using data from two multicenter, prospective cohorts of patients with HBV-ACLF, the discrimination, calibration, and clinical benefit were assessed for CPMs predicting 28-day and 90-day outcomes in patients with cirrhosis and those without, respectively.
A total of 919 patients with HBV-ACLF were identified by Chinese Group on the Study of Severe Hepatitis B (COSSH) criteria, including 675 with cirrhosis and 244 without. COSSH-ACLF IIs, COSSH-ACLFs, Chronic Liver Failure-Consortium Acute-on-Chronic Liver Failure score (CLIF-C ACLFs), Tongji Prognostic Predictor Model score (TPPMs), Model for End-Stage Liver Disease score (MELDs), and MELD-Sodium score (MELD-Nas) were all strong predictors of short-term mortality in patients with HBV-ACLF. In contrast to a high model discriminative capacity in ACLF without cirrhosis, each prognostic model represents a marked decline of C-index, net reclassification index (NRI), and integrated discrimination improvement (IDI) in predicting either 28-day or 90-day prognosis of patients with cirrhosis. The hazard analysis identified largely overlapping risk factors of poor outcomes in both subgroups, while serum bilirubin was specifically associated with short-term mortality in patients with cirrhosis and blood urea nitrogen in patients without cirrhosis. A subgroup analysis in patients with cirrhosis showed a decline of discrimination of CPMS in those with ascites or infections compared to that in those without.
Predicting the short-term outcome of HBV-ACLF by CPMs is optimal in patients without cirrhosis but limited in those with cirrhosis, at least partially due to the complicated ascites or infections.
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The 25Mg(p, γ)26Al reaction plays an important role in the study of cosmic 1.809 MeV γ-ray as a signature of ongoing nucleosynthesis in the Galaxy. At astrophysical temperature around ...0.1 GK, the 25Mg(p, γ)26Al reaction rates are dominated by the 92 keV resonance capture process. We report a precise measurement of the 92 keV 25Mg(p, γ)26Al resonance in the day-one experiment at Jinping Underground Nuclear Astrophysics experiment (JUNA) facility in the China Jinping Underground Laboratory (CJPL). The resonance strength and ground state feeding factor are determined to be 3.8±0.3 ×10−10 eV and 0.66±0.04, respectively. The results are in agreement with those reported in the previous direct underground measurement within uncertainty, but with significantly reduced uncertainties. Consequently, we recommend new 25Mg(p, γ)26Al reaction rates which are by a factor of 2.4 larger than those adopted in REACLIB database at the temperature around 0.1 GK. The new results indicate higher production rates of 26gAl and the cosmic 1.809 MeV γ-ray. The implication of the new rates for the understanding of other astrophysical situations is also discussed.
Electro-optic (EO) materials play a unique and crucial role in modern optical communication and laser science. However, EO materials with large EO coefficient are usually accompanied by serious ...piezoelectric ringing, which plays an important role in limiting their applications in high frequency and high voltage devices. It is difficult to find a balance between EO coefficient and piezoelectric coefficient. In this paper, we report a new EO crystal, K
3
Nb
3
B
2
O
12
(KNBO), acquired from a non-centrosymmetric antiferroelectric (AFE) material. Its EO coefficient is determined to be 3.3 pm V
−1
, which is comparable with the performance of the commercial EO crystals BBO (2.5 pm V
−1
) and LGS (2.3 pm V
−1
). The KNBO crystal exhibits high transmittance (nearly 80%) and a wide optical transparency range (from 327 nm to 4.67
μ
m). Moreover, the KNBO crystal could effectively avoid piezoelectric ringing, due to a negligible piezoelectric coefficient. These balanced properties of the KNBO crystal favor potential EO applications. More importantly, this is the first demonstration of linear EO modulation in an AFE crystal. This work opens the door for the exploration of AFEs as potential EO materials, which simultaneously possess large EO coefficients and overcome piezoelectric ringing.
A new EO crystal, K
3
Nb
3
B
2
O
12
, acquired from a non-centrosymmetric antiferroelectric material. Its EO effect mainly originates from atomic displacements (ionic contribution) under an external electric field.
Summary
Background
To date, 14 single‐nucleotide polymorphisms (SNPs) have been identified as susceptibility loci for chronic hepatitis B (CHB).
Aim
To investigate if these SNPs are associated with ...treatment response of hepatitis B e antigen (HBeAg)‐positive CHB patients.
Methods
We performed a retrospective analysis of 1623 Han Chinese HBeAg‐positive CHB patients (782 patients treated with pegylated interferon alpha PegIFNα for 48 weeks plus 24 weeks follow‐up, and 841 patients treated with nucleos(t)ide analogues NUCs for 104 weeks) included in four phase‐IV multicentre randomised controlled trials. All 14 SNPs were genotyped for each CHB patient. A polygenic score (PGS) was used to evaluate the cumulative effect of multiple SNPs. The associations of SNPs or PGS with combined response (CR) and hepatitis B s antigen (HBsAg) loss were assessed.
Results
We found that rs12614, a missense variant of complement factor B (CFB), was significantly associated with CR in PegIFNα‐treated patients, and the CR rate in patients with the rs12614 TT/CT genotype was less than one‐third of that in patients with the CC genotype (7.4% vs 22.6%, P = 0.009). Moreover, a PGS integrating CFB rs12614 and STAT4 rs7574865 (previously reported to be associated with response to PegIFNα) was significantly associated with both CR (P‐trend = 4.000 × 10−4) and HBsAg loss (P‐trend = 0.010) in PegIFNα‐treated patients. However, none of the SNPs were associated with treatment response in NUCs‐treated patients.
Conclusions
CFB rs12614 is an independent predictor of response to PegIFNα therapy in Chinese HBeAg‐positive CHB patients. A PGS integrating CFB rs12614 with STAT4 rs7574865 can effectively discriminate responders to PegIFNα from nonresponders.
Abstract
Except breast cancer and gastric cancer, HER2 gene amplification or overexpression is also expressed in other solid tumors, including but not limited to colorectal cancer (CRC), non-small ...cell lung cancer (NSCLC), gallbladder cancer, renal pelvis cancer and pancreatic cancer. The reports of immunotherapy combined with HER2-targeted therapy are limited. KN046 is a novel bispecific antibody that blocks both PD-L1 interaction with PD-1 and CTLA4 interaction with CD80/CD86. KN026 is a novel bispecific antibody that simultaneously binds to two distinct HER2 epitopes. Here the preliminary safety and efficacy results of KN046 in combination KN026 were reported in patients with locally advanced unresectable or metastatic other solid tumors who received ≥ 1 line prior systemic therapy.
Methods: HER2-positive locally advanced unresectable or metastatic other solid tumors with progression after ≥ 1 line of prior systemic therapy were recruited, including 14 CRC patients, 4 NSCLC patients, 4 gallbladder cancer patients, 1 renal pelvis cancer patient and 1 pancreatic cancer patient. These patients were by KN046 (iv. 5 mg/kg Q3W) plus KN026 (iv. 30 mg/kg Q3W, loading on C1D1, D8) until progression, unacceptable toxicity, or patient withdrawal. Efficacy was assessed according to RECIST 1.1 Q6W. The primary endpoint was objective response rate (ORR).
Results: As of the August 10th, 2021, 24 non-breast or non-gastric cancer patients with the median age of 56 years (range: 37-66) were enrolled. 20 and 24 patients were evaluable for overall response and safety, respectively. The ORR was 55.0% (11 of 20, 95% CI: 31.5-76.9). And the disease control rate (DCR) was 85.0% (17 of 20, 95% CI 62.1-96.8). The 6-month progression-free survival (PFS) rate was 84.1%. 11 CRC patients were evaluable for overall response. The ORR and DCR in CRC was 45.5% (5 of 11, 95% CI: 16.7-76.6) and 90.9% (10 of 11, 95% CI 58.7-99.8), respectively. Twenty of total 24(87.9%) patients suffered from treatment-related adverse events (TRAEs) of any grade. Total 4 of 24 (16.7%) patients had experienced ≥grade 3 TRAEs, including 4 cases related to KN046 and 3 cases related to KN026. The most common (≥10%) TRAEs were infusion related reaction (29.2%), diarrhea (19.4%), alanine aminotransferase increased (16.7%), aspartate aminotransferase increased (16.7%), vomiting(12.5%) and decreased appetite (12.5%). No treatment-related deaths were observed.
Conclusion: This chemotherapy-free regimen of KN046 in combination with KN026 has shown promising clinical efficacy and manageable toxicity in HER2-positive non-breast and non-gastric solid tumors with ≥ 1 line prior systemic therapy.
The trial is currently ongoing. ClinicalTrials.gov Number, NCT04521179
Citation Format: Jifang Gong, Lei Chen, Meili Sun, Yanming Zhang, Jieer Ying, Xiangcai Wang, Mingli Ni, Zhixiang Zhuang, Baohong Guo, Long Xiao, Summer Xia, Lin Shen. Preliminary safety and efficacy results of KN046 in combination with KN026 in patients with locally advanced unresectable or metastatic HER2-positive solid cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT542.
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