Uncommon presentation of acute type A aortic dissection: sleeve-severed and everted proximal right coronary artery intima without myocardial ischaemia.

BACKGROUND: Type A aortic dissection (TAAD) with coronary involvement is rare but potentially fatal. Proper myocardial protection during surgery is essential. CASE PRESENTATION: Here, we describe a 52-year-old woman who presented with sudden chest pain. CT angiography revealed TAAD with right coronary artery involvement. During surgery, the proximal intima of the right coronary artery was found to be completely severed and everted. Conventional myocardial perfusion methods were inadequate. A patented perfusion tip for coronary artery orifice perfusion was used, resulting in favourable surgical outcomes. The patient was discharged without complications. CONCLUSIONS: This case emphasizes the need for careful preoperative assessment of coronary involvement in TAAD patients. The myocardial protection method used here is very helpful and can be applied effectively in similar cases encountered by surgeons.

Natural Linoleic Acid from Marine Fungus Eutypella sp. F0219 Blocks KEAP1/NRF2 Interaction and Ameliorates MASLD by Targeting FABP4.

Ectopic lipid accumulation induced lipotoxicity plays a crucial role in exacerbating the development of metabolic dysfunction-associated steatotic liver disease (MASLD), which affects over 30% of the worldwide population and 85% of the obese population. The growing demand for effective therapeutic agents highlights the need for high-efficacy lipotoxicity ameliorators and relevant therapeutic targets in the fight against MASLD. This study aimed to discover natural anti-lipotoxic and anti-MASLD candidates and elucidate the underlying mechanism and therapeutic targets. Utilizing palmitic acid (PA)-induced HepG-2 and primary mouse hepatocyte models, we identified linoleic acid (HN-002), a ligand of fatty acid binding protein 4 (FABP4), from the marine fungus Eutypella sp. F0219. HN-002 dose-dependently prevented lipid overload-induced hepatocyte damage and lipid accumulation, inhibited fatty acid esterification, and ameliorated oxidative stress. These beneficial effects were associated with improvements in mitochondrial adaptive oxidation. HN-002 treatment enhanced lipid transport into mitochondria and oxidation, inhibited mitochondrial depolarization, and reduced mitochondrial ROS (mtROS) level in PA-treated hepatocytes. Mechanistically, HN-002 treatment disrupted the interaction between KEAP1 and NRF2, leading to NRF2 deubiquitylation and nuclear translocation, which activated beneficial metabolic regulation. In vivo, HN-002 treatment (20 mg/kg/per 2 days, i. p.) for 25 days effectively reversed hepatic steatosis and liver injury in the fast/refeeding plus high-fat/high-cholesterol diet induced MASLD mice. These therapeutic effects were associated with enhanced mitochondrial adaptive oxidation and activation of NRF2 signaling in the liver. These data suggest that HN-002 would be an interesting candidate for MASLD by improving mitochondrial oxidation via the FABP4/KEAP1/NRF2 axis. The discovery offers new insights into developing novel anti- MASLD agents derived from marine sources.

Effect of single blastocyst-stage versus single cleavage-stage embryo transfer on cumulative live births in women with good prognosis undergoing in vitro fertilization: Multicenter Randomized Controlled Trial.

In this multicenter, non-inferiority, randomized trial, we randomly assigned 992 women undergoing in-vitro fertilization (IVF) with a good prognosis (aged 20-40, ≥3 transferrable cleavage-stage embryos) to strategies of blastocyst-stage (n = 497) or cleavage-stage (n = 495) single embryo transfer. Primary outcome was cumulative live-birth rate after up to three transfers. Secondary outcomes were cumulative live-births after all embryo transfers within 1 year of randomization, pregnancy outcomes, obstetric-perinatal complications, and livebirths outcomes. Live-birth rates were 74.8% in blastocyst-stage group versus 66.3% in cleavage-stage group (relative risk 1.13, 95%CI:1.04-1.22; Pnon-inferiority < 0.001, Psuperiority = 0.003) (1-year cumulative live birth rates of 75.7% versus 68.9%). Blastocyst transfer increased the risk of spontaneous preterm birth (4.6% vs 2.0%; P = 0.02) and neonatal hospitalization >3 days. Among good prognosis women, a strategy of single blastocyst transfer increases cumulative live-birth rates over single cleavage-stage transfer. Blastocyst transfer resulted in higher preterm birth rates. This information should be used to counsel patients on their choice between cleavage-stage and blastocyst-stage transfer (NCT03152643, https://clinicaltrials.gov/study/NCT03152643 ).

Modulation of Melanocyte in Melasma Patients After Picosecond Laser Treatment.

BACKGROUND: Melasma is a therapeutically challenging hyperpigmented skin condition. Currently, there is a lack of in vivo observation regarding changes in melanin and dendritic melanocytes after laser treatment. OBJECTIVE: To investigate alterations in melanin and melanocytes in melasma before and after laser treatment using optical coherence tomography (OCT). METHODS: Eight female melasma patients were enrolled in Taiwan. Based on the baseline OCT scans, the patients were categorized into either epidermal-type or mixed-type melasma and were assigned different treatment protocols accordingly. Sequential OCT images were collected from melasma lesions and normal skin at baseline, Week 4 and Week 8. RESULTS: After 8 weeks of laser treatment, the mean Melasma Area Severity Index (MASI) score improved from 10.92 to 6.30. Results from OCT showed no significant changes in the normalized density, area, or intensity of melanin in both lesional and normal skin. At baseline, the mean length of dendritic melanocytes in the affected skin was 15% longer than those in normal skin; at Week 8, the mean length of lesional dendritic melanocytes became the same as those in normal skin. Additionally, the mean width of dendritic melanocytes decreased from being 4% wider to only 2% wider than those in normal skin. CONCLUSION: After 8 weeks of treatment, an improvement of MASI score was noted, mainly attributable to a reduction in lesional area. OCT showed no notable change regarding melanin, but a decrease in length and width of dendritic melanocytes was noted in the lesional skin of melasma patients.

GATA factor TRPS1, a new DNA repair protein, cooperates with reversible PARylation to promote chemoresistance in breast cancer patients.

Resistance to DNA-damaging agents is a major unsolved challenge for breast cancer patients undergoing chemotherapy. Here, we show that elevated expression of transcriptional repressor GATA binding 1 (TRPS1) is associated with lower drug sensitivity, reduced response rate, and poor prognosis in chemotherapy-treated breast cancer patients. Mechanistically, elevated TRPS1 expression promotes hyperactivity of DNA damage repair (DDR) in breast cancer cells. We provide evidence that TRPS1 dynamically localizes to DNA breaks in a Ku70- and Ku80-dependent manner, and that TRPS1 is a new member of the DDR protein family. We also discover that the dynamics of TRPS1 assembly at DNA breaks is regulated by its reversible PARylation in the DDR, and that mutations of the PARylation sites on TRPS1 lead to increased sensitivity to chemotherapeutic drugs. Taken together, our findings provide new mechanistic insights into the DDR and chemoresistance in breast cancer patients and identify TRPS1 as a critical DDR protein. TRPS1 may also be considered as a target to improve chemo-sensitization strategies and, consequently, clinical outcomes for breast cancer patients.

Application of Ward Noise Management in Perioperative Hepatobiliary Surgery: A Retrospective Study.

OBJECTIVE: To explore the application effect of ward noise management during the perioperative period of hepatobiliary surgery. METHODS: The clinical data of 295 patients undergoing hepatobiliary surgery admitted to People's Hospital of Zunyi City Bo Zhou District from March 2020 to March 2023 were retrospectively analyzed. In accordance with different perioperative management programs, patients were divided into the control (implementation of perioperative routine management) and observation (implementation of perioperative routine management + ward noise management) groups. Patients' general data were matched through propensity score matching, and 55 cases were allocated to each group. After matching, the clinical indicators of the two groups were compared to evaluate the effect of ward noise management on patients undergoing hepatobiliary surgery. RESULTS: No significant difference in general data was found between the two groups (P > 0.05). After management, the postoperative recovery indicators, such as feeding time, exhaust time, defecation time, first time to get out of bed, and incidence of postoperative complications, did not significantly differ between the observation and control groups (P > 0.05). The Hamilton Anxiety Scale, Hamilton Depression Scale and Pittsburgh Sleep Quality Index scores of the observation group were lower than those of the control group (P < 0.05). The average noise decibel values during the day, night, and over 24 hours of the observation group were lower than those of the control group (P < 0.05). CONCLUSIONS: Ward noise management can improve the negative emotions of patients undergoing hepatobiliary surgery, enhance sleep quality, and promote recovery. Therefore, it has a certain clinical promotion value.

Restoration of ARA metabolic disorders in vascular smooth muscle cells alleviates intimal hyperplasia.

Intimal hyperplasia (IH) is an innegligible issue for patients undergoing interventional therapy. The proliferation and migration of vascular smooth muscle cells (VSMCs) induced by platelet-derived growth factor-BB (PDGF-BB) are critical events in the development of IH. While the exact mechanism and effective target for IH needs further investigation. Metabolic disorders of arachidonic acid (ARA) are involved in the occurrence and progression of various diseases. In this study, we found that the expressions of soluble epoxide hydrolase (sEH) and cyclooxygenase-2 (COX-2) were significantly increased in the VSMCs during balloon injury-induced IH. Then, we employed a COX-2/sEH dual inhibitor PTUPB to increase the concentration of epoxyeicosatrienoic acids (EETs) while prevent the release of pro-inflammatory prostaglandins. Results showed that PTUPB treatment significantly reduced neointimal thickening induced by balloon injury in rats in vivo and inhibited PDGF-BB-induced proliferation and migration of VSMCs in vitro. Our results showed that PTUPB may reverse the phenotypic transition of VSMCs by inhibiting Pttg1 expression. In conclusion, we found that the dysfunction of ARA metabolism in VSMCs contributes to IH, and the COX-2/sEH dual inhibitor PTUPB attenuates IH progression by reversing the phenotypic switch in VSMC through the Sirt1/Pttg1 pathway.

Gut microbiota mediate early life stress-induced social dysfunction and anxiety-like behaviors by impairing amino acid transport at the gut.

Early life stress alters gut microbiota and increases the risk of neuropsychiatric disorders, including social deficits and anxiety, in the host. However, the role of gut commensal bacteria in early life stress-induced neurobehavioral abnormalities remains unclear. Using the maternally separated (MS) mice, our research has unveiled a novel aspect of this complex relationship. We discovered that the reduced levels of amino acid transporters in the intestine of MS mice led to low glutamine (Gln) levels in the blood and synaptic dysfunction in the medial prefrontal cortex (mPFC). Abnormally low blood Gln levels limit the brain's availability of Gln, which is required for presynaptic glutamate (Glu) and γ-aminobutyric acid (GABA) replenishment. Furthermore, MS resulted in gut microbiota dysbiosis characterized by a reduction in the relative abundance of Lactobacillus reuteri (L. reuteri). Notably, supplementation with L. reuteri ameliorates neurobehavioral abnormalities in MS mice by increasing intestinal amino acid transport and restoring synaptic transmission in the mPFC. In conclusion, our findings on the role of L. reuteri in regulating intestinal amino acid transport and buffering early life stress-induced behavioral abnormalities provide a novel insight into the microbiota-gut-brain signaling basis for emotional behaviors.

Design, Synthesis, and Antifeedant Activity Evaluation of 13/14-Arylthioether Matrine Derivatives.

Introducing a sulfur atom into active agricultural molecules is an important strategy for pesticide development. Matrine, an environmentally friendly botanical pesticide, has the advantage of being easily degraded and has drawn attention in the agricultural field. To explore the novel matrine-type pesticides, in this study, we designed and synthesized 13/14-arylthioether matrine derivatives by introducing various aryl sulfide motifs into bioactive matrine. Most of the synthesized arylthioether matrines exhibited good antifeedant activity against Spodoptera exigua. Among them, compound 2q showed the best antifeedant effect with an EC50 value of 0.038 mg/mL, which is approximately 125-fold more activity than matrine and reached the activity level of commercial standard azadirachtin A. Furthermore, compound 2q exhibited an inhibitory effect on antifeedant-related enzyme carboxylesterase (CarE) from S. exigua. In short, the high activity of arylthioether matrines offers new insights into developing new antifeedants.

Pseudo-continuous and territorial arterial spin labeling MRI for assessment of cerebral perfusion in moyamoya disease after revascularization: A comparative study with digital subtraction angiography.

Purpose: To evaluate if pseudo-continuous arterial spin labeling (pcASL) and territorial ASL (tASL) can assess cerebral perfusion post-revascularization in Moyamoya disease and compare with digital subtraction angiography (DSA) outcomes. Materials and methods: Patients diagnosed with Moyamoya disease who underwent pcASL using two post-labeling delays (short ASL, 1,525 ms; delayed ASL, 2,525 ms), tASL, and DSA 3 months after surgery at a single institution were retrospectively evaluated. Manual delineation on pcASL cerebral blood flow (CBF) maps covered middle cerebral artery (MCA) territory on both sides, and cerebellum. Normalized CBF (nCBF) was calculated. Revascularization in the MCA territory was evaluated with external carotid angiography and tASL, graded on a three-point scale. Intermodality agreement was analyzed with weighted κ statistics. Correlation between pcASL-derived nCBF and tASL-measured revascularization, and revascularization grade from direct angiography, was determined. Diagnostic performance of pcASL and tASL was evaluated using DSA as a reference via receiver operating characteristic (ROC) curve analysis. Results: A total of 32 hemispheres from 31 patients were assessed. On the operated side, sASL and dASL had nCBF values of 1.00 ± 0.30 and 1.31 ± 0.31, respectively. Revascularization area grading showed substantial intermodality agreement (weighted κ = 0.68; 95 % CI: 0.49, 0.87). DSA revascularization moderately correlated with sASL and dASL nCBF values (r = 0.56 and 0.47) and strongly correlated with tASL revascularization area (r = 0.73). ROC analysis revealed that sASL and dASL nCBF values reflected revascularization (area under the curve (AUC) = 0.86 and 0.77) and tASL revascularization area (AUC = 0.91). Combined pcASL and tASL had an AUC of 0.93, comparable to tASL alone, improving diagnostic performance. The diagnostic accuracy of nCBF for sASL was 87.5 %, superior to 75 % for dASL. The diagnostic accuracy of tASL external carotid artery revascularization area was 87.5 %, with sensitivity and specificity of 88 % and 85.7 %, respectively. Conclusion: The combination of pcASL and tASL outperformed pcASL alone in assessing cerebral perfusion post-Moyamoya disease revascularization.

π-Extension of Multiple Resonance Core: Double Helical and Heptagon Embedded Nanographenes.

Multiple resonance (MR) boron-nitrogen doped polycyclic aromatic hydrocarbons (BN-PAHs) showed compelling thermally activated delayed fluorescence (TADF), surpassing those of their hydrocarbon analogs. However, the structural variety of π-extended BN-PAHs remains narrow. In this study, we synthesized three double helical BN-doped nanographenes (BN-NGs), 2a-2c, via the π-extension of the MR core. During the formation of 2a, a nanographene with one heptagon (1a) was obtained, whereas subsequent dehydrocyclization of the [6]helicene units within 2b-2c led to heptagon structures, yielding other two BN-NGs containing double heptagons (1b-1c). These BN-NGs (2a-2c and 1a-1c) showed pronounced redshifts of 100-190 nm compared to the parent MR core while preserving the TADF characteristics and prolonging the delayed fluorescence lifetime to the millisecond level. Furthermore, the integration of heptagon ring into 1a-1c expanded the conjugation, reduced the oxidation potentials, and yielded a more flexible framework compared to those of 2a-2c. The enantiomers of 2a-2c, 1a, and 1c were resolved and their chiroptical properties were studied. Notably, 1a and 1c exhibited the increased chiroptical dissymmetry factors.

lncRNA H19 facilitates vascular neointima formation by targeting miR-125a-3p/FLT1 axis.

The aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to the development of neointima formation in vascular restenosis. This study aims to explore the function of the long noncoding RNA H19 in neointima formation. A mouse carotid ligation model was established, and human vascular smooth muscle cells (VSMCs) were used as a cell model. lncRNA H19 overexpression promoted VSMC proliferation and migration. Moreover, miR-125a-3p potentially bound to lncRNA H19, and Fms-like tyrosine kinase-1 (FLT1) might be a direct target of miR-125a-3p in VSMCs. Upregulation of miR-125a-3p alleviated lncRNA H19-enhanced VSMC proliferation and migration. Furthermore, rescue experiments showed that enhanced expression of miR-125a-3p attenuated lncRNA H19-induced FLT1 expression in VSMCs. In addition, the overexpression of lncRNA H19 significantly exacerbated neointima formation in a mouse carotid ligation model. In summary, lncRNA H19 stimulates VSMC proliferation and migration by acting as a competing endogenous RNA (ceRNA) of miR-125a-3p. lncRNA H19 may be a therapeutic target for restenosis.

Knowledge-reinforced explainable next basket recommendation.

The next basket recommendation task aims to predict the items in the user's next basket by modeling the user's basket sequence. Existing next basket recommendations focus on improving recommendation performance, and most of these methods are black-box models, ignoring the importance of providing explanations to improve user satisfaction. Furthermore, most next basket recommendation methods are designed for consumer users, and few methods are proposed for business user characteristics. To address the above problems, we propose a Knowledge Reinforced Explainable Next Basket Recommendation (KRE-NBR). Specifically, we construct a basket-based knowledge graph and obtain pretrained embeddings of entities that contain rich information of the knowledge graph. To obtain high-quality user predictive vectors, we fuse user pretrained embeddings, user basket sequence level embeddings, and user repurchase embeddings. One highlight of the user repurchase embeddings is that they are able to model business user repurchase behavior. To make the results of next basket recommendations explainable, we use reinforcement learning for path reasoning to find the items recommended in the next basket and generate recommendation explanations at the same time. To the best of our knowledge, this is the first work to provide recommendation explanations for next basket recommendations. Extensive experiments on real datasets show that the recommendation performance of our proposed approach outperforms several state-of-the-art baselines.

A 12-year comparison of patients with Alzheimer's dementia with their informants in eight Asian countries.

BACKGROUND: The number of patients with Alzheimer's disease (AD) has increased dramatically in Asia. OBJECTIVE: To update the demographic characteristics of patients with AD and their informants in eight Asian countries and compare them from 12 years prior. METHODS: The A1-A3 components of the Uniform Dataset (UDS), version 3.0, were administered in Taiwan, Beijing, Hong Kong, Korea, Japan, Philippines, Thailand, and Indonesia. Data were compared with patients with AD in the first registration using the UDS version 1.0 from 2010-2014 in the same regions. RESULTS: A total of 1885 patients with AD and their informants were recruited from 2022 to 2024 and were compared with 2042 patients recruited a decade prior. Each country had its own unique characteristics that changed between both eras. The mean age of the patients and informants was 79.8±8.2 years and 56.5±12.1 years, respectively. Compared with the first registration, the patients were older (79.8 vs 79.0, p=0.002) and had worse global function (mean CDR-SB scores 6.1 vs 5.8, p<0.001); more informants were children (56 % vs. 48 %, p<0.001), and their frequency of in-person visits increased significantly if not living together. A total of 11 %, 4.5 %, 11 %, and 0.4 % of the patients had a reported history of cognitive impairment in their mothers, fathers, siblings, and children, respectively; all percentages, except children, increased significantly over the past decade. CONCLUSION: The present study reports the heterogeneous characteristics of patients with AD and their informants in Asian countries, and the distinct changes in the past decade. The differences in dementia evaluation and care between developing and developed countries warrant further investigation.

Precisely Tunable Instantaneous Carbon Rearrangement Enables Low-Working-Potential Hard Carbon Toward Sodium-Ion Batteries with Enhanced Energy Density.

As the preferred anode material for sodium-ion batteries, hard carbon (HC) confronts significant obstacles in providing a long and dominant low-voltage plateau to boost the output energy density of full batteries. The critical challenge lies in precisely enhancing the local graphitization degree to minimize Na+ ad-/chemisorption, while effectively controlling the growth of internal closed nanopores to maximize Na+ filling. Unfortunately, traditional high-temperature preparation methods struggle to achieve both objectives simultaneously. Herein, a transient sintering-involved kinetically-controlled synthesis strategy is proposed that enables the creation of metastable HCs with precisely tunable carbon phases and low discharge/charge voltage plateaus. By optimizing the temperature and width of thermal pulses, the high-throughput screened HCs are characterized by short-range ordered graphitic micro-domains that possess accurate crystallite width and height, as well as appropriately-sized closed nanopores. This advancement realizes HC anodes with significantly prolonged low-voltage plateaus below 0.1 V, with the best sample exhibiting a high plateau capacity of up to 325 mAh g-1. The energy density of the HC||Na3V2(PO4)3 full battery can therefore be increased by 20.7%. Machine learning study explicitly unveils the "carbon phase evolution-electrochemistry" relationship. This work promises disruptive changes to the synthesis, optimization, and commercialization of HC anodes for high-energy-density sodium-ion batteries.

Study of condensable particulate matter from stationary combustion sources: Source profiles, emissions, and impact on ambient fine particulate matter.

Although significant progress has been made in controlling emissions from stationary combustion sources in China over the past decade, understanding of condensable particulate matter (CPM) emissions from these sources and their impact on ambient PM2.5 remains limited. In this study, we established the source profiles and emission inventories of CPM from coal-fired industrial boilers (CFIBs), coal-fired power plants (CFPPs), and iron and steel industry (ISIs) for the Yangtze River Delta (YRD) region of China; furthermore, the air quality model (Community Multiscale Air Quality, CMAQ) was used to evaluate the impact of CPM emissions from these three types of stationary combustion sources on ambient PM2.5 during Feb. 2018, a month characterized by elevated PM2.5 concentrations. The results indicated that CPM emissions from these three sources in the YRD region before and after the implementation of the ultra-low emissions (ULE) policy amounted to 109,839 and 43,338 tons, respectively, with particularly high emission intensity along the Yangtze River. The implementation of CFPPs ULE policy was shown to reduce the impact of CPM emissions from these three stationary sources on monthly PM2.5 concentrations from 0.92 µg/m3 to 0.41 µg/m3 (with a maximum of 5.35 µg/m3). This reduction exceeded the 0.31 µg/m3 decrease in PM2.5 concentrations resulting from the emission reductions of conventional pollutants (FPM, SO2 and NOx). CPM emissions from these three stationary sources were found to increase the PM2.5 by 0.68 µg/m3 during pollution periods. The largest components of PM2.5 contributed by CPM emissions from stationary combustion sources were sulfate, organic carbon, and nitrate, accounting for 21.4 %, 21.1 %, and 18.2 %, respectively. Particularly, contributions from CPM emissions to PM2.5 varied by altitude, with a relatively large impact at altitudes between 220 and 460 m. Attention should be given to CPM emission control, with particular priority placed on implementing ULE measures for ISIs and CFIBs.

ADP-glucose pyrophosphorylase gene family in soybean and implications in drought stress tolerance.

BACKGROUND: ADP-glucose pyrophosphorylase (AGPase) is the key rate-limiting enzyme in starch biosynthesis pathway, and has been identified as a potential target for manipulation strategies aimed at improving crop yield and quality. OBJECTIVE: To identify the AGPase gene family members in soybean, and explore the potential implications of GmAGPS2 in drought stress tolerance. METHODS: The genome-wide identification and sequence analysis of soybean AGPase gene family was carried out by bioinformatics methods. The GmAGP gene expression was analyzed using transcriptome data and quantitative real-time PCR (qRT-PCR). Furthermore, transgenic yeast strains overexpressing GmAGPS2 were generated, and their growth was observed under drought stress. RESULTS: In this study, we searched for AGPase genes (GmAGP) in the soybean genome and identified a total of 14 GmAGP genes. The GmAGP proteins had a unique conserved NTP_transferase domain and were mainly located in the chloroplast and cytosol. Evolutionarily, the GmAGP proteins can be clustered into two distinct subgroups; within the same subgroup, they displayed a similar distribution pattern of conserved motifs. The GmAGP genes exhibited an uneven distribution on 10 chromosomes, and segmental duplication contributed to AGPase gene family expansion in soybean. The GmAGP genes presented different tissue expression pattern, in which GmAGPL6, GmAGPL9, and GmAGPL10 mainly exhibited tissue-specific expression pattern. The promoter of GmAGP genes had multiple cis-acting elements related to phytohormones and stress responses, and 8 GmAGP genes contained drought-responsive cis-acting elements. qRT‒PCR analysis demonstrated a significant upregulation expression of GmAGPL6, GmAGPL10, and GmAGPS2 in response to drought stress. Further functional analysis indicated that GmAGPS2 gene could improve yeast growth under drought stress conditions and enhance the drought tolerance of yeast. CONCLUSION: These results will contribute to further elucidation of the function of GmAGP genes, and offer important candidate genes for the genetic improvement of starch and yield-related traits and the breeding of high drought stress tolerance varieties in soybean.

NDRG1 enhances the sensitivity to Cetuximab by promoting Stat1 ubiquitylation in colorectal cancer.

INTRODUCTION: Cetuximab (CTX) is an effective targeted drug for the treatment of metastatic colorectal cancer, but it is effective only in patients with wild-type KRAS genes. Even in this subset of patients, the sensitivity of CTX in patients with right hemi-colon cancer is much lower than that in patients with left hemi-colon cancer. This significantly limits its clinical application. Therefore, further elucidation of the underlying molecular mechanisms is needed. N-myc downstream-regulated gene 1 (NDRG1) plays an important role in solid tumor invasion and metastasis, but whether it can influence CTX sensitivity has not been thoroughly investigated. OBJECTIVE: Our study aimed to identify a novel mechanism by which NDRG1 affects CTX sensitivity. METHODS: Through mass spectrometry analysis of our previously constructed CTX-resistant RKO and HCT116 cells, we found that the signal transducer and activator of transcription-1 (Stat1) might be a potential target of NDRG1. By knocking out NDRG1 or/and Stat1 genes, we then applied the loss-of-function experiments to explore the regulatory relationship between NDRG1 and Stat1 and their roles in the cell cycle, epithelial-mesenchymal transition (EMT), and the sensitivity to CTX in these two colorectal cancer (CRC) cells. Finally, we used the nude-mouse transplanted tumor model and human CRC samples to verify the expression of NDRG1 and Stat1 and their impact on CTX sensitivity in vivo. RESULTS: Stat1 was upregulated in CTX-resistant cells, whereas NDRG1 was downregulated. Mechanically, NDRG1 was inversely correlated with Stat1 expression. It suppressed CRC cell proliferation, migration, and invasion, and promoted apoptosis and epithelial-mesenchymal transition (EMT) by inhibiting Stat1. In addition, NDRG1 directly interacted with Stat1 and promoted Smurf1-induced Stat1 ubiquitination. Importantly, this novel NDRG1-dependent regulatory loop also enhanced CTX sensitivity both in vitro and in vivo. CONCLUSION: Our study revealed that NDRG1 enhanced the sensitivity to Cetuximab by inhibiting Stat1 expression and promoting its ubiquitination in colorectal cancer, elucidating NDRG1 might be a potential therapeutic target for refractory CTX-resistant CRC tumors. But its clinical value still needs to be validated in a larger sample size as well as a different genetic background.

l-Homoproline-Directed Synthesis of Organic-Inorganic Metal Iodides for Second Harmonic Generation.

Three organic-inorganic metal iodides, namely, (NH4)(l-hp)ZnI3 (1), [Cd(l-hp)4]Cd3I8 (2), and (l-Hhp)(l-hp)PbI3 (3), have been synthesized using l-homoproline (l-hp) as the structure-directing agent. These compounds feature different noncentrosymmetric structures and optical properties. In particular, compound 3 shows a large second-harmonic-generation response of 3.4 times that of KH2PO4. Density functional theory calculations were performed to gain insight into its structure-property relationship.

Long wavelength near-infrared and red light-driven consecutive photo-induced electron transfer for highly effective photoredox catalysis.

Consecutive photoinduced electron transfer (conPET) processes accumulate the energies of two photons to overcome the thermodynamic limit of traditional photoredox catalysis. However, the excitation wavelength of conPET systems mainly focused on short wavelength visible light, leading to photodamage and incompatibility with large-scale reactions. Herein, we report on conPET systems triggered by near-infrared (NIR) and red light. Specifically, a blue-absorbing conPET photocatalyst, perylene diimide (PDI) is sensitized by a palladium-based photosensitizer to triplet excited state (3PDI*), which generates PDI radical anion (PDI•-) over 100-fold faster than that in the conventional conPET. Accordingly, photoreduction with superior reaction rate and penetration depth, as well as reduced photodamage is detected. More importantly, our work offers comprehensive design rules for the triplet-mediated conPET strategy, whose versatility is confirmed by metal-free dye pairs and NIR-active PtTNP/PDI. Notably, our work achieves NIR-driven atom transfer radical polymerization using an inert aromatic halide as the initiator.