Scutellarin alleviates renal ischemia-reperfusion injury by inhibiting the MAPK pathway and pro-inflammatory macrophage polarization.

Renal ischemia-reperfusion injury (IRI) is an integral process in renal transplantation, which results in compromised graft survival. Macrophages play an important role in both the early inflammatory period and late fibrotic period in response to IRI. In this study, we investigated whether scutellarin (SCU) could protect against renal IRI by regulating macrophage polarization. Mice were given SCU (5-50 mg/kg) by gavage 1 h earlier, followed by a unilateral renal IRI. Renal function and pathological injury were assessed 24 h after reperfusion. The results showed that administration of 50 mg/kg SCU significantly improved renal function and renal pathology in IRI mice. In addition, SCU alleviated IRI-induced apoptosis. Meanwhile, it reduced macrophage infiltration and inhibited pro-inflammatory macrophage polarization. Moreover, in RAW 264.7 cells and primary bone marrow-derived macrophages (BMDMs) exposed to SCU, we found that 150 µM SCU inhibited these cells to polarize to an inflammatory phenotype induced by lipopolysaccharide (LPS) and interferon-γ (IFN-γ). However, SCU has no influence on anti-inflammatory macrophage polarization in vivo and in vitro induced by in interleukin-4 (IL-4). Finally, we explored the effect of SCU on the activation of the mitogen-activated protein kinase (MAPK) pathway both in vivo and in vitro. We found that SCU suppressed the activation of the MAPK pathway, including the extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK), and p38. Our results demonstrated that SCU protects the kidney against IRI by inhibiting macrophage infiltration and polarization toward pro-inflammatory phenotype via the MAPK pathway, suggesting that SCU may be therapeutically important in treatment of IRI.

Multi-gene phylogenetic analyses revealed two novel species and one new record of Trichobotrys (Pleosporales, Dictyosporiaceae) from China.

The rotting wood in freshwater is a unique eco-environment favoring various fungi. During our investigation of freshwater fungi on decaying wood, three hyphomycetes were collected from Jiangxi and Guangxi Provinces, China. Based on the morphological observations and phylogenetic analysis of a combined DNA data containing ITS, LSU, SSU and tef1-α sequences, two new Trichobotrys species, T.meilingensis and T.yunjushanensis, as well as a new record of T.effusa, were introduced. Additionally, a comprehensive description of the genus with both morphological and molecular data was first provided.

Giant nonlinear Hall and wireless rectification effects at room temperature in the elemental semiconductor tellurium.

The second-order nonlinear Hall effect (NLHE) in non-centrosymmetric materials has recently drawn intense interest, since its inherent rectification could enable various device applications such as energy harvesting and wireless charging. However, previously reported NLHE systems normally suffer from relatively small Hall voltage outputs and/or low working temperatures. In this study, we report the observation of a pronounced NLHE in tellurium (Te) thin flakes at room temperature. Benefiting from the semiconductor nature of Te, the obtained nonlinear response can be readily enhanced through electrostatic gating, leading to a second-harmonic output at 300 K up to 2.8 mV. By utilizing such a giant NLHE, we further demonstrate the potential of Te as a wireless Hall rectifier within the radiofrequency range, which is manifested by the remarkable and tunable rectification effect also at room temperature. Extrinsic scattering is then revealed to be the dominant mechanism for the NLHE in Te, with symmetry breaking on the surface playing a key role. As a simple elemental semiconductor, Te provides an appealing platform to advance our understanding of nonlinear transport in solids and to develop NLHE-based electronic devices.

Assessment of Coronary Involvement with MDCT and Long-term Outcomes in Patients with Takayasu's Arteritis.

RATIONALE AND OBJECTIVES: Takayasu's arteritis (TA) mainly affects the aorta and its branches involving the coronary arteries. Coronary CT angiography can be used to detect coronary artery lesions. Outcome of TA patients with coronary involvement has not been well established. Our study aimed to systematically analyze coronary lesions in patients with TA and to access long-term outcome in TA patients with coronary involvement. MATERIALS AND METHODS: A retrospective cohort study of TA patients with coronary CT angiography was conducted between January 2009 and October 2021. Baseline clinical characteristics, laboratory parameters, imaging features and therapeutic features were collected and analyzed. Follow-up was scheduled since the onset of TA. Overall survival and major adverse cardiovascular events (MACE) were analyzed in patients with coronary lesions. RESULTS: 48 (59.3%) TA patients had coronary involvement. Coronary ostial stenosis was detected in 31 (64.6%) patients by MDCT. Prevalence of disease activity (p = 0.007) was higher in patients with ostial stenosis. The median follow-up was 10.0 years. Death was observed in nine patients including seven died from myocardial infarction. TA patients with ostial stenosis had higher rate of MACE (p = 0.013). Baseline activity(HR: 5.250, 95%CI 2.004-8.639), ostial involvement(HR:8.954, 95%CI 3.875-56.038), stenosis≥ 70% (HR: 10.822, 95%CI 2.764-61.230) and activity recurrence (HR:11.913, 95%CI 2.321-85.747) were independently associated with increased major cardiovascular events. CONCLUSION: MDCT should be performed in patients suspected with coronary involvement to make early diagnosis. Myocardial ischemia is the major cause of longterm death in TA patients with coronary lesions. Baseline disease activity, coronary ostial stenosis, stenosis ≥ 70% and activity recurrence were independent risk factors of cardiovascular events in TA patients.

Clinical features and prognostic factors of patients with inoperable hepatocellular carcinoma treated with chemotherapy: a population-based study.

Background: In inoperable hepatocellular carcinoma (HCC), chemotherapy is a common treatment strategy. However, there is a lack of reliable methods to predict the prognosis of patients with inoperable HCC after chemotherapy. Therefore, the aim of this study was to identify the clinical characteristics of patients with inoperable HCC and to establish and validate nomogram models for predicting the survival outcomes in this patient group following chemotherapy. Methods: The data of patients diagnosed with HCC from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively collected. Logistic regression analyses were used to identify potential factors for inoperability in patients with HCC. Kaplan-Meier analyses were applied to evaluate the impact of chemotherapy on prognosis. Additionally, Cox regression analyses were performed to identify the potential risk factors associated with overall survival (OS) and cancer-specific survival (CSS) in patients with inoperable HCC treated with chemotherapy. Finally, we constructed prognostic nomograms for predicting the 1- and 3-year survival probabilities. Results: A total of 3,519 operable patients with HCC and 4,656 patients with inoperable HCC were ultimately included in this study. Logistic regression analyses revealed a significant association between patient age, gender, race, tumor, node, metastasis (TNM) stage, tumor size, pretreatment alpha fetoprotein (AFP) levels, and marital status with inoperability. Moreover, Kaplan-Meier analyses revealed a significant improvement in both OS and CSS with the administration of chemotherapy. Moreover, 1,456 patients with inoperable HCC were enrolled in the training group and 631 patients with inoperable HCC were enrolled in the validation group to develop and validate the prognostic models. Cox regression models indicated that TNM stage, tumor size, and pretreatment AFP were independent risk factors for predicting OS and CSS in patients with inoperable HCC receiving chemotherapy. These factors were subsequently integrated into the predictive nomograms. Conclusions: We preliminarily developed survival models with strong predictive capabilities for estimating survival probabilities in patients with HCC following chemotherapy. These models hold potential for clinical application and warrant further exploration through additional studies.

Ancestral origins and admixture history of Kazakhs.

Kazakh people, like many other populations that settled in Central Asia, demonstrate an array of mixed anthropological features of East Eurasian (EEA) and West Eurasian (WEA) populations, indicating a possible scenario of biological admixture between already differentiated EEA and WEA populations. However, their complex biological origin and genomic makeup, as well as their genetic interaction with surrounding populations, are not well understood. In an attempt to decipher their genetic structure and population history, we conducted, to our knowledge, the first whole-genome sequencing study of Kazakhs residing in Xinjiang (KZK). We demonstrated that KZK derived their ancestries from four ancestral source populations: East Asian (∼39.7%), West Asian (∼28.6%), Siberian (∼23.6%), and South Asian (∼8.1%). The recognizable interactions of EEA and WEA ancestries in Kazakhs were dated back to the 15th century BCE. Kazakhs were genetically distinctive from Uyghurs in terms of their overall genomic makeup, although the two populations were closely related in genetics, and both showed a substantial admixture of EEA and WEA ancestries. Notably, we identified a considerable sex-biased admixture, with an excess of western males and eastern females contributing to the KZK gene pool. We further identified a set of genes that showed remarkable differentiation in KZK from the surrounding populations, including those associated with skin color (SLC24A5, OCA2), essential hypertension (HLA-DQB1), hypertension (MTHFR, SLC35F3), and neuron development (CNTNAP2). These results advance our understanding of the complex history of contacts between Western and Eastern Eurasians, especially those situated along the old Silk Road.

SEC61 translocon gamma subunit is correlated with glycolytic activity, epithelial mesenchymal transition and the immune suppressive phenotype of lung adenocarcinoma.

Lung adenocarcinoma (LUAD) remains a predominant cause of cancer-related mortality globally, underscoring the urgency for targeted therapeutic strategies. The specific role and impact of the SEC61 translocon gamma subunit (SEC61G) in LUAD progression and metastasis remain largely unexplored. In this study, we use a multifaceted approach, combining bioinformatics analysis with experimental validation, to elucidate the pivotal role of SEC61G and its associated molecular mechanisms in LUAD. Our integrated analyses reveal a significant positive correlation between SEC61G expression and the glycolytic activity of LUAD, as evidenced by increased fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/CT scans. Further investigations show the potential influence of SEC61G on metabolic reprogramming, which contributes to the immunosuppressive tumor microenvironment (TME). Remarkably, we identify a negative association between SEC61G expression levels and the infiltration of critical immune cell populations within the TME, along with correlations with immune checkpoint gene expression and tumor heterogeneity scores in LUAD. Functional studies demonstrate that SEC61G knockdown markedly inhibits the migration of A549 and H2030 LUAD cells. This inhibitory effect is accompanied by a significant downregulation of key regulators of tumor progression, including hypoxia-inducible factor-1 alpha (HIF-1α), lactate dehydrogenase A, and genes involved in the epithelial-mesenchymal transition pathway. In conclusion, our comprehensive analyses position SEC61G as a potential prognostic biomarker intricately linked to glycolytic metabolism, the EMT pathway, and the establishment of an immune-suppressive phenotype in LUAD. These findings underscore the potential of SEC61G as a therapeutic target and predictive marker for immunotherapeutic responses in LUAD patients.

Deficiency of m 6 A RNA methylation promotes ZBP1-mediated cell death.

m 6 A RNA methylation suppresses the immunostimulatory potential of endogenous RNA. Deficiency of m 6 A provokes inflammatory responses and cell death, but the underlying mechanisms remain elusive. Here we showed that the noncoding RNA 7SK gains immunostimulatory potential upon m 6 A depletion and subsequently activates the RIG-I/MAVS axis to spark interferon (IFN) signaling cascades. Concomitant excess of IFN and m 6 A deficiency synergistically facilitate the formation of RNA G-quadruplexes (rG4) to promote ZBP1-mediated necroptotic cell death. Collectively, our findings delineate a hitherto uncharacterized mechanism that links m 6 A dysregulation with ZBP1 activity in triggering inflammatory cell death.

Discovery of N'-benzyl-3-chloro-N-((1S,3R,4R)-3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)cyclohexyl)benzenesulfonamide as a novel selective KOR ligand.

The effective management of moderate to severe pain often relies on the use of analgesic agents. However, the widespread utility of these medications is hindered by the occurrence of several undesirable side effects. In light of this challenge, there is growing interest in the development of κ opioid receptor (KOR) agonists, which have shown promise in mitigating these adverse effects. In this study, leveraging the structural scaffold of compound D (our previous study), we embarked on the design, synthesis, and evaluation of a series of N'-benzyl-3-chloro-N- ((1S,3R,4R)-3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)cyclohexyl)benzenesulfonamide derivatives. These compounds were subjected to comprehensive in vitro and in vivo test. Through systematic structure-activity relationship (SAR) exploration, we successfully identified compound 23p (Ki(KOR):1.9 nM) as a highly selective KOR ligand of new chemotype. 23p showed high clearance in vitro PK test, and abdominal contraction test showed potent antinociceptive effect. 23p and its O-demethyl metabolite 25 were both found in the plasma of mouse, 25 also showed potent affinity toward KOR (Ki(KOR): 3.1 nM), both they contribute to the analgesic effect. Moreover, 23p exhibited potent antinociceptive activity in abdominal constriction test, which was effectively abolished by pre-treatment of nor-BNI, a selective KOR antagonist.

Coronary Atherosclerosis Progression Provides Incremental Prognostic Value and Optimizes Risk Reclassification by Computed Tomography Angiography.

PURPOSE: This study investigated the prognostic value and risk reclassification ability of coronary atherosclerosis progression through serial coronary computed tomography angiography (CCTA). MATERIALS AND METHODS: This study enrolled patients with suspected or confirmed coronary artery disease who underwent serial CCTA. Coronary atherosclerosis progression was represented by coronary artery calcium score (CACS) and segment stenosis score (SSS) progression. The baseline and follow-up CCTA characteristics and coronary atherosclerosis progression were compared. Furthermore, the incremental prognostic value and reclassification ability of three models (model 1, baseline risk factors; model 2, model 1 + SSS; and model 3, model 2 + SSS progression) for major adverse cardiovascular events (MACEs) were compared. RESULTS: In total, 516 patients (aged 56.40 ± 9.56 y, 67.4% men) were enrolled. During a mean follow-up of 65.29 months, 114 MACE occurred. The MACE group exhibited higher CACS and SSS than the non-MACE group at baseline and follow-up CCTA (P < 0.001), and demonstrated higher coronary atherosclerosis progression than the non-MACE group (ΔSSS: 2.63 ± 2.50 vs 1.06 ± 1.78, P < 0.001; ΔCACS: 115.15 ± 186.66 vs 89.91 ± 173.08, P = 0.019). SSS progression provided additional prognostic information (C-index = 0.757 vs 0.715, P < 0.001; integrated discrimination index = 0.066, P < 0.001) and improved the reclassification ability of risk (categorical-net reclassification index = 0.149, P = 0.015) compared with model 2. CONCLUSIONS: Coronary atherosclerosis progression through CCTA significantly increased the prognostic value and risk stratification for MACE compared with baseline risk factor evaluation and CCTA only.

Introducing carbon assimilation in yeasts using photosynthetic directed endosymbiosis.

Conversion of heterotrophic organisms into partially or completely autotrophic organisms is primarily accomplished by extensive metabolic engineering and laboratory evolution efforts that channel CO2 into central carbon metabolism. Here, we develop a directed endosymbiosis approach to introduce carbon assimilation in budding yeasts. Particularly, we engineer carbon assimilating and sugar-secreting photosynthetic cyanobacterial endosymbionts within the yeast cells, which results in the generation of yeast/cyanobacteria chimeras that propagate under photosynthetic conditions in the presence of CO2 and in the absence of feedstock carbon sources like glucose or glycerol. We demonstrate that the yeast/cyanobacteria chimera can be engineered to biosynthesize natural products under the photosynthetic conditions. Additionally, we expand our directed endosymbiosis approach to standard laboratory strains of yeasts, which transforms them into photosynthetic yeast/cyanobacteria chimeras. We anticipate that our studies will have significant implications for sustainable biotechnology, synthetic biology, and experimentally studying the evolutionary adaptation of an additional organelle in yeast.

Comparison of femoral tunnel position and knee function in anterior cruciate ligament reconstruction: a retrospective cohort study using measuring-fluoroscopy method versus bony marker method.

BACKGROUND: Previous studies have shown that surgical technique errors especially the wrong bone tunnel position are the primary reason for the failure of anterior cruciate ligament (ACL) reconstruction. In this study, we aimed to compare the femoral tunnel position and impact on knee function during the ACL reconstruction using measuring combined with fluoroscopy method and bony marker method for femoral tunnel localization. METHODS: A retrospective cohort study of patients undergoing ACL reconstruction using the bony marker method or measuring combined with fluoroscopy for femoral tunnel localization was conducted between January 2015 and January 2020. A second arthroscopic exploration was performed more than 1 year after surgery. Data regarding patient demographics, the femoral tunnel position, results of the Lysholm score, the International Knee Documentation Committee (IKDC) score, KT-1000 side-to-side difference, pivot shift grade, and Lachman grade of the knee were collected. RESULTS: A total of 119 patients were included in the final cohort. Of these, 42 cases were in the traditional method group, and 77 cases were in the measuring method group. The good tunnel position rate was 26.2% in the traditional method group and 81.8% in the measuring method group (p < 0.001). At the final follow-up, the Lysholm and IKDC scores were significantly greater in the measuring method group than the traditional method group (IKDC: 84.9 ± 8.4 vs. 79.6 ± 6.4, p = 0.0005; Lysholm: 88.8 ± 6.4 vs. 81.6 ± 6.4, p < 0.001). Lachman and pivot shift grades were significantly greater in the measuring method group (p = 0.01, p = 0008). The results of KT-1000 side-to-side differences were significantly better in the measuring method group compared with those in the traditional method group (p < 0.001). CONCLUSIONS: The combination of the measuring method and intraoperative fluoroscopy resulted in a concentrated tunnel position on the femoral side, a high rate of functional success, improved knee stability, and a low risk of tunnel deviation. This approach is particularly suitable for surgeons new to ACL reconstructive surgery.

[Establishment of a humanized mouse model of HIV-1 infection and quantification of integrated HIV proviral DNA in vivo].

In recent years, virological, pathological, and immunological studies need to be carried out for the emerging anti-human immunodeficiency virus (HIV) therapies such as gene therapy, broadly neutralizing antibodies, and the derived chimeric antigen receptor (CAR)-T immunotherapy, which necessitates suitable, simple, and inexpensive small-animal models and methods for accurate quantification of the viral genome in the HIV-1 infected. In our research, the HIV-∆ENV-Jurkat-EGFP-mCherry cell line was engineered through the infection with a dual-labelled HIV pseudovirus. A nested quantitative PCR (nested-qPCR) method with the cellular genome as the integrated standard was established for the quantification of HIV proviral copies. We administered intravenous injections of healthy human peripheral blood mononuclear cell (PBMC) into NOD/Prkdcscid/IL2rgnull (NPG) mice. To verify engraftment kinetics, we analyzed the percentages of hCD45+, hCD3+, hCD4+, and hCD8+ cells in the peripheral blood of hu-PBMC-NPG mice. To evaluate HIV-1 infection in hu-PBMC-NPG mice, we inoculated these mice with HIV NL4-3-NanoLuc by intraperitoneal (IP) injection. We then monitored the luciferase expression by the small animal imaging system and measured the viral load in the spleen by qPCR. The infiltration of human PBMCs in mice was detected 3-5 weeks after intravenous injection, and the percentage of hCD45 in humanized mouse PBMCs were more than 25% five weeks after IP inoculation. The expression of the virus-associated luciferase protein was detected by luciferase imaging 27 days post infection. Moreover, the viral total DNA, RNA, and proviral DNA copies reached 18 000 copies/106 cells, 15 000 copies/µg RNA, and 15 000 copies/106 cells, respectively, in the mouse spleen. Taken together, we reported a convenient method for building a simple humanized mouse model of HuPBMC-NPG/severe combined immunodeficiency (SCID) by intravenous injection with hu-PBMCs without advanced surgical skills and irradiation. Furthermore, we established a convenient method for the efficient determination of proviral DNA to assess HIV replication in vivo, viral reservoir sizes, and efficacy of novel anti-HIV therapies including CAR-T immunotherapy and gene therapy.

Fracture behavior of additively manufactured corrax maraging stainless steel.

Additively manufactured a low carbon Fe-Cr-Ni-Al Corrax stainless steel has ultra-high strength, but the mechanism at work when the steel cracks is still unclear. In this study, Corrax stainless steel was tensile tested to fracture and cracks in the vicinity of the fracture surface were analyzed by scanning electron microscope and electron-backscattered diffraction. The results show that the cracks propagated at angles of 45-60° to the tensile axis. Some cracks were transgranular, and high-angle grain boundaries had little effect on crack propagation. Crack propagation was inhibited in regions with lower Taylor factors. Kernel average misorientation value analysis established that the crack propagation process is accompanied by significant plastic deformation. The influence of particles and unfused pores on crack propagation is also discussed.

[Mechanism of astragaloside â £ modulation of Nrf2/HO-1/GPX4 pathway to inhibit ferroptosis and ameliorate atherosclerosis in ApoE~(-/-) mice].

The intervention effect of astragaloside Ⅳ(AS-Ⅳ) on atherosclerosis in apolipoprotein E gene knockout(ApoE)~(-/-) mice was observed based on the nuclear factor erythroid-2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4) signaling pathway to explore the potential mechanism of AS-Ⅳ in improving ferroptosis in atherosclerotic mice. This study established an atherosclerosis mouse model by feeding them a high-fat diet. After modeling for 8 weeks, ApoE~(-/-) mice were randomly divided into the model group, AS-Ⅳ group, AS-Ⅳ+Nrf2 inhibitor(ML385) group, and ferrostatin-1(Fer-1) group. Additionally, a blank control group was also established. Corresponding drugs were administered via intraperitoneal injection, with the control group receiving an equivalent amount of normal saline injection as the model group. After the experiment, serum biochemical levels were measured using an automatic blood lipid analyzer, hematoxylin-eosin(HE) staining was used to observe morphological changes in aortic sinus tissues, colorimetric methods were used to detect levels of ferrous ion(Fe~(2+)), malondialdehyde(MDA), glutathione(GSH), and superoxide dismutase(SOD) in mouse serum, immunofluorescence was used to observe the expressions of ferritin heavy chain 1(FTH1) and ferritin light chain(FTL) proteins in the aortic sinus of mice, Western blot was used to detect the protein levels of Nrf2, HO-1, and GPX4 in mouse aortic tissues, and transmission electron microscopy was used to observe ultrastructural changes in aortic tissues. RESULTS:: showed that compared to the control group, the model group of mice had significantly increased calcification and plaque deposition areas in the aortic sinus, increased mitochondrial membrane density, decreased or disappeared mitochondrial cristae, elevated levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), Fe~(2+), and MDA, decreased levels of high-density lipoprotein cholesterol(HDL-C), SOD, and GSH, and significant inhibition of Nrf2, HO-1, GPX4 proteins, as well as iron storage proteins FTH1 and FTL expressions in the aorta. Compared to the model group, AS-Ⅳ treatment resulted in decreased serum TC, TG, LDL-C, Fe~(2+), and MDA levels, increased HDL-C, SOD, and GSH levels, increased expressions of Nrf2, HO-1, and GPX4 proteins, and iron storage proteins FTH1 and FTL, and significant improvement in aortic tissue morphology. Compared to the AS-Ⅳ group, the Nrf2 inhibitor ML385 could reverse the therapeutic effect of AS-Ⅳ on atherosclerosis mice. These findings suggest that AS-Ⅳ can inhibit ferroptosis and improve atherosclerosis in ApoE~(-/-) mice, and its mechanism of action may be related to the regulation of the Nrf2/HO-1/GPX4 signaling pathway.

Genome-wide analysis of the SWEET gene family in Hemerocallis citrina and functional characterization of HcSWEET4a in response to salt stress.

Sugars will be eventually effluxed transporters (SWEETs) have been confirmed to play diverse physiological roles in plant growth, development and stress response. However, the characteristics and functions of the SWEET genes in Hemerocallis citrina remain unclear and poorly elucidated. In this study, the whole genome of Hemerocallis citrina was utilized to conduct bioinformatics analysis and a total of 19 HcSWEET genes were successfully identified. Analysis of the physicochemical properties indicated dominant differences among these HcSWEETs. A phylogenetic analysis revealed that HcSWEET proteins can be divided into 4 clades ranging from Clade I to IV, where proteins within the same clade exhibited shared conserved motifs and gene structures. Five to six exons were contained in the majority of HcSWEET genes, which were unevenly distributed across 11 chromosomes. The gene duplication analysis showed the presence of 4 gene pairs. Comparative syntenic maps revealed that the HcSWEET gene family might present more closed homology in monocotyledons than dicotyledons. Cis-acting element analysis of HcSWEET genes indicated key responsiveness to various hormones, light, and stresses. Additionally, transcriptome sequencing analysis suggested that most HcSWEET genes had a relatively higher expression in roots, and HcSWEET4a was significantly up-regulated under salt stress. Overexpression further verified the possibility that HcSWEET4a was involved in response to salt stress, which provides novel insights and facilitates in-depth studies of the functional analysis of HcSWEETs in resistance to abiotic stress.

Surface photogalvanic effect in Ag2Te.

The bulk photovoltaic effect (BPVE) in non-centrosymmetric materials has attracted significant attention in recent years due to its potential to surpass the Shockley-Queisser limit. Although these materials are strictly constrained by symmetry, progress has been made in artificially reducing symmetry to stimulate BPVE in wider systems. However, the complexity of these techniques has hindered their practical implementation. In this study, we demonstrate a large intrinsic photocurrent response in centrosymmetric topological insulator Ag2Te, attributed to the surface photogalvanic effect (SPGE), which is induced by symmetry reduction of the surface. Through diverse spatially-resolved measurements on specially designed devices, we directly observe that SPGE in Ag2Te arises from the difference between two opposite photocurrent flows generated from the top and bottom surfaces. Acting as an efficient SPGE material, Ag2Te demonstrates robust performance across a wide spectral range from visible to mid-infrared, making it promising for applications in solar cells and mid-infrared detectors. More importantly, SPGE generated on low-symmetric surfaces can potentially be found in various systems, thereby inspiring a broader range of choices for photovoltaic materials.

Discovery of a peptide proteolysis-targeting chimera (PROTAC) drug of p300 for prostate cancer therapy.

BACKGROUND: The E1A-associated protein p300 (p300) has emerged as a promising target for cancer therapy due to its crucial role in promoting oncogenic signaling pathways in various cancers, including prostate cancer. This need is particularly significant in prostate cancer. While androgen deprivation therapy (ADT) has demonstrated promising efficacy in prostate cancer, its long-term use can eventually lead to the development of castration-resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC). Notably, p300 has been identified as an important co-activator of the androgen receptor (AR), highlighting its significance in prostate cancer progression. Moreover, recent studies have revealed the involvement of p300 in AR-independent oncogenes associated with NEPC. Therefore, the blockade of p300 may emerge as an effective therapeutic strategy to address the challenges posed by both CRPC and NEPC. METHODS: We employed AI-assisted design to develop a peptide-based PROTAC (proteolysis-targeting chimera) drug that targets p300, effectively degrading p300 in vitro and in vivo utilizing nano-selenium as a peptide drug delivery system. FINDINGS: Our p300-targeting peptide PROTAC drug demonstrated effective p300 degradation and cancer cell-killing capabilities in both CRPC, AR-negative, and NEPC cells. This study demonstrated the efficacy of a p300-targeting drug in NEPC cells. In both AR-positive and AR-negative mouse models, the p300 PROTAC drug showed potent p300 degradation and tumor suppression. INTERPRETATION: The design of peptide PROTAC drug targeting p300 is feasible and represents an efficient therapeutic strategy for CRPC, AR-negative prostate cancer, and NEPC. FUNDING: The funding details can be found in the Acknowledgements section.

Observing the Role of Electron Delocalization in Electronic Transport by Incorporating Actinides into Ligated Metal-Chalcogenide Superatoms.

Since delocalization of electronic states is a prerequisite for exerting unique electron transport properties, early actinides (An) with highly delocalized 5f/6d orbitals are natural candidates. However, given the experimental difficulties of such radioactive compounds and the complex relativistic effects in theoretical studies, understanding the electronic structure and bonding of actinides is underdeveloped on the periodic table. A further challenge is the very complicated electronic structures encountered in the confinement of actinides, as vividly illustrated by the weakly radioactive Th(Thorium)-encapsulated metal chalcogenide clusters, Th@Co6Te8L6 (L = PH3, PMe3, PEt3). Here we report the electronic structure and the electron transport properties of the Th@Co6Te8L6 clusters and compare them with those of the hollow Co6Te8L6 clusters using the nonequilibrium Green's function combined with relativistic density functional theory (NEGF-DFT). We found that the equilibrium conductance in Th@Co6Te8(PH3)6 (0.76 G0) has been greatly improved over that in Co6Te8(PH3)6 (0.03 G0), which has also been verified under an applied different bias voltage. The covalent bonding character between 6d (Th) and 3d (Co) atomic orbitals resulting from steric confinement is the source of the performance enhancement and a most important factor governing the accessibility of such 5f/6d orbitals. The results are of significance to the rapidly developing field of molecular nanoelectronics.