The effects of a mixture of small peptide chelating minerals and inorganic minerals on the production performance and tissue deposition of broiler chickens.

Due to the limited bioavailability of inorganic trace minerals, their utilization in poultry production has led to problems such as environmental contamination and inefficient resource utilization. It was investigated whether replacing inorganic trace minerals (ITM) with a blend of organic small peptide-chelated trace minerals (MIX) would improve production performance, selected biochemical parameters, antioxidant capacity, mineral deposition in liver, heart, and tibia, as well as mineral content in feces of broilers. A total of 432 healthy 21-day-old 817 broilers were randomly divided into 4 groups with 6 replicates per group and 18 chickens per replicate. The control group received a basal diet supplemented with 1,000 mg/kg of inorganic trace minerals as sulfate. The experimental groups received basal diets supplemented with 200, 400, and 600 mg/kg of mixed trace mineral elements (50% sulfate +50% small peptide-chelate) for a trial period of 30 days, divided into two stages: 21-35 days and 36-50 days. The results indicate that on the 50th day, compared with the 1,000 mg/kg ITM group, the levels of serum cholesterol, urea nitrogen, and malondialdehyde in the 200, 400, and 600 mg/kg MIX groups decreased (p < 0.01), while the levels of serum glutathione peroxidase in the 200, 400, and 600 mg/kg MIX groups increased (p < 0.05). Compared to the ITM group, the addition of organic small peptide chelated trace minerals mixed with inorganic trace minerals can reduce the levels of zinc and manganese in feces (p < 0.01). Furthermore, the iron content in the heart and tibia of the 600 mg/kg MIX group also significantly decreased (p < 0.05). There were no differences in growth performance and slaughter performance among the groups (p > 0.05). This study shows that replacing inorganic minerals with low-dose MIX (200, 400, and 600 mg/kg) can reduce the levels of zinc and manganese in feces, with no negative impact on growth and slaughter performance.

Efficacy and safety of antibiotics for treatment of leptospirosis: a systematic review and network meta-analysis.

BACKGROUND: Leptospirosis, an important zoonotic bacterial disease, commonly affects resource-poor populations and results in significant morbidity and mortality worldwide. The value of antibiotics in leptospirosis remains unclear, as evidenced by the conflicting opinions published. METHODS: We conducted a search in the PubMed, Web of Science, and Cochrane Library databases for studies. These studies included clinical trials and retrospective studies that evaluated the efficacy or safety of antibiotics for leptospirosis treatment. The primary outcomes assessed were defervescence time, mortality rate, and hospital stays. Subgroup analyses were performed based on whether there were cases involving children and whether there were cases of severe jaundice. Safety was defined as the prevalence of adverse events associated with the use of antibiotics. p scores were utilized to rank the efficacy of the antibiotics. RESULTS: There are included 9 randomized controlled trials (RCTs), 1 control trial (CT), and 3 retrospective studies (RS) involving 920 patients and 8 antibiotics. Six antibiotics resulted in significantly shorter defervescence times compared to the control, namely cefotaxime (MD, - 1.88; 95% CI = - 2.60 to - 1.15), azithromycin (MD, - 1.74; 95% CI = - 2.52 to - 0.95), doxycycline (MD, - 1.53; 95% CI = - 2.05 to - 1.00), ceftriaxone (MD, - 1.22; 95% CI = - 1.89 to - 0.55), penicillin (MD, - 1.22; 95% CI = - 1.80 to - 0.64), and penicillin or ampicillin (MD, - 0.08; 95% CI = - 1.01 to - 0.59). The antibiotics were not effective in reducing the mortality and hospital stays. Common adverse reactions to antibiotics included Jarisch-Herxheimer reaction, rash, headache, and digestive reactions (nausea, vomiting, diarrhea, abdominal pain, and others). CONCLUSIONS: Findings recommend that leptospirosis patients be treated with antibiotics, which significantly reduced the leptospirosis defervescence time. Cephalosporins, doxycycline, and penicillin are suggested, and azithromycin may be a suitable alternative for drug-resistant cases. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022354938.

Graphene-integrated mesh electronics with converged multifunctionality for tracking multimodal excitation-contraction dynamics in cardiac microtissues.

Cardiac microtissues provide a promising platform for disease modeling and developmental studies, which require the close monitoring of the multimodal excitation-contraction dynamics. However, no existing assessing tool can track these multimodal dynamics across the live tissue. We develop a tissue-like mesh bioelectronic system to track these multimodal dynamics. The mesh system has tissue-level softness and cell-level dimensions to enable stable embedment in the tissue. It is integrated with an array of graphene sensors, which uniquely converges both bioelectrical and biomechanical sensing functionalities in one device. The system achieves stable tracking of the excitation-contraction dynamics across the tissue and throughout the developmental process, offering comprehensive assessments for tissue maturation, drug effects, and disease modeling. It holds the promise to provide more accurate quantification of the functional, developmental, and pathophysiological states in cardiac tissues, creating an instrumental tool for improving tissue engineering and studies.

New sesquiterpenoids from Biscogniauxia sp.

Five new sesquiterpenoids, including a campherenane-type (1), a bergamotane-type (2), a drimane-type (3), and two bisabolane-type (5-6) sesquiterpenoids have been isolated from Biscogniauxia sp. 71-10-1-1. Their structures were determined by spectroscopic analyses, quantum chemical ECD calculations,13C chemical shifts calculations, and X-ray crystallography. This is the first report of campherenane-type and drimane-type sesquiterpenoids from Biscogniauxia. Furthermore, the anti-inflammatory assays of all compounds are evaluated, and the results showed that compounds 3 and 7 exhibited the effects against the production of the pro-inflammatory cytokine TNF-α.

Heterozygous CAPZA2 mutations cause global developmental delay, hypotonia with epilepsy: a case report and the literature review.

CAPZA2 encodes the α2 subunit of CAPZA, which is vital for actin polymerization and depolymerization in humans. However, understanding of diseases associated with CAPZA2 remains limited. To date, only three cases have been documented with neurodevelopmental abnormalities such as delayed motor development, speech delay, intellectual disability, hypotonia, and a history of seizures. In this study, we document a patient who exhibited seizures, mild intellectual disability, and impaired motor development yet did not demonstrate speech delay or hypotonia. The patient also suffered from recurrent instances of respiratory infections, gastrointestinal and allergic diseases. A novel de novo splicing variant c.219+1 G > A was detected in the CAPZA2 gene through whole-exome sequencing. This variant led to exon 4 skipping in mRNA splicing, confirmed by RT-PCR and Sanger sequencing. To our knowledge, this is the third study on human CAPZA2 defects, documenting the fourth unambiguously diagnosed case. Furthermore, this splicing mutation type is reported here for the first time. Our research offers additional support for the existence of a CAPZA2-related non-syndromic neurodevelopmental disorder. Our findings augment our understanding of the phenotypic range associated with CAPZA2 deficiency and enrich the knowledge of the mutational spectrum of the CAPZA2 gene.

Cav-1 regulates the bile salt export pump on the canalicular membrane of hepatocytes by PKCα-associated signalling under cholesterol stimulation.

BACKGROUND AND AIMS: The secretion of bile salts transported by the bile salt export pump (BSEP) is the primary driving force for the generation of bile flow; thus, it is closely related to the formation of cholesterol stones. Caveolin-1 (Cav-1), an essential player in cell signalling and endocytosis, is known to co-localize with cholesterol-rich membrane domains. This study illustrates the role of Cav-1 and BSEP in cholesterol stone formation. METHODS: Adult male C57BL/6 mice were used as an animal model. HepG2 cells were cultured under different cholesterol concentrations and BSEP, Cav-1, p-PKCα and Hax-1 expression levels were determined via Western blotting. Expression levels of BSEP and Cav-1 mRNA were detected using real-time PCR. Immunofluorescence and immunoprecipitation assays were performed to study BSEP and Hax-1 distribution. Finally, an ATPase activity assay was performed to detect BSEP transport activity under different cholesterol concentrations in cells. RESULTS: Under low-concentration stimulation with cholesterol, Cav-1 and BSEP protein and mRNA expression levels significantly increased, PKCα phosphorylation significantly decreased, BSEP binding capacity to Hax-1 weakened, and BSEP function increased. Under high-concentration stimulation with cholesterol, Cav-1 and BSEP protein and mRNA expression levels decreased, PKCα phosphorylation increased, BSEP binding capacity to Hax-1 rose, and BSEP function decreased. CONCLUSION: Cav-1 regulates the bile salt export pump on the canalicular membrane of hepatocytes via PKCα-associated signalling under cholesterol stimulation.

Clinical and Animal Studies of Waist and Knee Scraping Therapy for Knee Osteoarthritis.

BACKGROUND: Knee osteoarthritis (KOA) is a degenerative condition with knee pain as the main clinical manifestation. Scraping is one of the commonly used traditional Chinese medicine treatment methods, which activates blood circulation, removes blood stasis, reduces inflammation, and so on. Although scholars have proposed that the synergistic treatment of the waist and knee for KOA is superior to simple knee treatment, there is no relevant reference literature on the application of scraping therapy. Therefore, this study aims to explore the effectiveness and potential mechanisms of waist and knee scraping therapy for treating KOA through clinical and animal studies in order to promote its clinical application. OBJECTIVE: To explore the clinical efficacy of waist and knee scraping therapy in the treatment of KOA from clinical study and increase animal study on this basis to preliminarily explore its mechanism, providing an objective basis for better treatment of KOA. METHOD: The clinical study recruited 90 KOA patients and divided them into a control group, a knee scraping group, and a waist and knee scraping group using a random number table method. All patients were evaluated for clinical efficacy, the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), and Traditional Chinese Medicine Syndrome Score. The KOA rat model was established using the Hulth method. The rats were randomly divided into a control group, KOA group, waist scraping group, knee scraping group, and waist and knee scraping group. During the intervention process of rats, the pain sensitivity threshold was measured, and HE staining was performed on the synovium and cartilage. The protein and mRNA expression levels of TNF-α, IL- 1ß, IL-6, PGP9.5, SP and TRPA1, TRPV4, SP, and NGF were measured by Western blot and real-time PCR. RESULTS: In the clinical study, the clinical efficacy of the 2 scraping groups was significantly higher than that of the control group. The clinical efficacy of the waist and knee scraping group on the 60th day of treatment was significantly higher than that of the knee scraping group. In terms of improving WOMAC scores, all 3 groups had significance; The function and total score of the waist and knee scraping group on the 28th day of treatment, as well as the pain, function, and total score on the 60th day, were lower than those of the knee scraping group. In terms of improving pain while standing, pain when walking on flat ground, and total score, the scraping group had significant differences. The score of heavy limbs in the waist and knee scraping group was lower than that in the knee scraping group. In an animal study, during the 4th week after modeling, there were differences in the pain sensitivity threshold between the KOA group and the waist scraping group compared to the control group, while there were differences in the pain sensitivity threshold between the knee scraping group and the waist and knee scraping group compared to the KOA group. The expression levels of various proteins and genes in the KOA group and waist scraping group increased compared to the control group; The knee scraping group and the waist and knee scraping group were lower than those in the KOA group. CONCLUSION: Scraping therapy can significantly alleviate knee joint pain and stiffness, improve joint function, and improve clinical efficacy, and the short-term and long-term effects of waist and knee scraping therapy are more significant. The scraping therapy has a definite therapeutic effect on KOA rats, which can improve the threshold of cold hyperalgesia and mechanical hyperalgesia, and the waist and knee scraping therapy is more obvious. This may be related to reducing inflammatory reactions in synovial and ganglion tissues. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR230070623.

Resistance to Cholesterol Gallstone Disease: Hepatic Cholesterol Metabolism.

Cholesterol gallstone disease (CGD) is one of the most common digestive diseases, and it is closely associated with hepatic cholesterol metabolism. Cholesterol gallstones may be caused by abnormal hepatic cholesterol metabolism, such as excessive cholesterol biosynthesis within the liver, interfering with the uptake or export of cholesterol in the liver, and abnormal hepatic cholesterol esterification. In this review, we begin with a brief overview of the clinical diagnosis and treatment of gallstone disease (GSD). Then, we briefly describe the major processes of hepatic cholesterol metabolism and summarize the key molecular expression changes of hepatic cholesterol metabolism in patients with gallstones. We review and analyze the recent advances in elucidating the relationships between these key molecules and CGD, and some targets significantly impacting on CGD via hepatic cholesterol metabolism are also listed. We also provide a significant discussion on the relationship between CGD and nonalcoholic fatty liver disease (NAFLD). Finally, the new discoveries of some therapeutic strategies associated with hepatic cholesterol metabolism to prevent and treat CGD are summarized.

CHMP3 promotes the progression of hepatocellular carcinoma by inhibiting caspase­1­dependent pyroptosis.

Charged multivesicular body protein 3 (CHMP3) is an elemental constituent of the endosomal sorting complex required for transport (ESCRT) III, whose function as a tumor susceptibility gene in the development of liver cancer remains unclear. CHMP3 was found to be associated with pyroptosis by bioinformatics analysis of data from patients with hepatocellular carcinoma (HCC) in The Cancer Genome Atlas database. It was aimed to explore the role and potential mechanisms of CHMP3 in the development of liver cancer. The expression of CHMP3 at the tissue level was examined using immunohistochemistry and western blot analysis. Subsequently, HepG2 and Huh­7 cells were transfected with small interfering RNA and overexpression plasmids to change CHMP3 expression. The proliferative capacity of cells was examined using colony formation and Cell Counting Kit­8 assays. Wound healing and Transwell assays were used to examine the migratory and invasive abilities of the cells. Transmission electron microscopy was used to observe changes in cell morphology. Western blotting was used to examine the expression of caspase­1 signaling pathway related proteins, a classic pathway of pyroptosis. In addition, a xenograft tumor model was used to examine the tumorigenic ability of CHMP3 in vivo. The results demonstrated that CHMP3 expression was upregulated in HCC and was associated with poor prognosis. Knockdown or overexpression of CHMP3 inhibited or promoted the proliferation, migration and invasion of liver cancer cells. Knockdown of Huh­7 showed changes in cell membrane integrity as well as cytoplasmic leakage. Furthermore, knockdown of CHMP3 may activate the caspase­1 pyroptosis signaling pathway which in turn inhibits the progression of liver cancer, and this effect can be reversed by the caspase­1 inhibitor AYC. In conclusion, CHMP3 may affect the development of liver cancer through the caspase­1­mediated pyroptosis pathway.

Low-Temperature Vapor-Phase Growth of 2D Metal Chalcogenides.

2D metal chalcogenides (MCs) have garnered significant attention from both scientific and industrial communities due to their potential in developing next-generation functional devices. Vapor-phase deposition methods have proven highly effective in fabricating high-quality 2D MCs. Nevertheless, the conventionally high thermal budgets required for synthesizing 2D MCs pose limitations, particularly in the integration of multiple components and in specialized applications (such as flexible electronics). To overcome these challenges, it is desirable to reduce the thermal energy requirements, thus facilitating the growth of various 2D MCs at lower temperatures. Numerous endeavors have been undertaken to develop low-temperature vapor-phase growth techniques for 2D MCs, and this review aims to provide an overview of the latest advances in low-temperature vapor-phase growth of 2D MCs. Initially, the review highlights the latest progress in achieving high-quality 2D MCs through various low-temperature vapor-phase techniques, including chemical vapor deposition (CVD), metal-organic CVD, plasma-enhanced CVD, atomic layer deposition (ALD), etc. The strengths and current limitations of these methods are also evaluated. Subsequently, the review consolidates the diverse applications of 2D MCs grown at low temperatures, covering fields such as electronics, optoelectronics, flexible devices, and catalysis. Finally, current challenges and future research directions are briefly discussed, considering the most recent progress in the field.

A key protein from Borrelia burgdorferi could stimulate cytokines in human microglial cells and inhibitory effects of Cucurbitacin IIa.

Lyme neuroborreliosis (LNB) is an infectious disease of the nervous system caused by Borrelia burgdorferi (Bb) infection. However, its pathogenesis is not fully understood. We used recombinant BmpA (rBmpA) to stimulate human microglia cell HMC3, then collected the culture supernatant and extracted total RNA from cells, and used the supernatant for cytokine chip, then ELISA and qPCR technology were used to validate the results from cytokine chip. After rBmpA stimulation of microglia, 24 inflammation-related cytokines showed elevated expression. Among them, six cytokines (IL-6, IL-8, CCL2, CCL5, CXCL1, and CXCL10) increased significantly in mRNA transcription, three cytokines (IL-6, IL-8, and CXCL10) concentrations in the cell supernatant increased significantly after the rBmpA stimulation, and CuIIa could inhibit expression of these cytokines. The BmpA can stimulate human microglia to produce large amounts of cytokines, leading to the occurrence of inflammation, which may be closely related to the development of LNB. CuIIa can inhibit BmpA-induced cytokine production in microglia, which may have potential therapeutic effects on LNB.

High-Performance Complementary Circuits from Two-Dimensional MoTe2.

Two-dimensional (2D) materials hold great promise for future complementary metal-oxide semiconductor (CMOS) technology. However, the lack of effective methods to tune the Schottky barrier poses a challenge in constructing high-performance complementary circuits from the same material. Here, we reveal that the polarity of pristine MoTe2 field-effect transistors (FETs) with minimized air exposure is n-type, irrespective of the metal contact type. The fabricated n-FETs with palladium contact can reach electron currents up to 275 µA/µm at VDS = 2 V. For p-FETs, we introduce a novel nitric oxide doping strategy, allowing a controlled transition of MoTe2 FETs from n-type to unipolar p-type. By doping only in the contact region, we demonstrate hole currents up to 170 µA/µm at VDS= -2 V with preserved Ion/Ioff ratios of 105. Finally, we present a complementary inverter circuit comprising the high-performance n- and p-type FETs based on MoTe2, promoting the application of 2D materials in future electronic systems.

Cascaded compression of size distribution of nanopores in monolayer graphene.

Monolayer graphene with nanometre-scale pores, atomically thin thickness and remarkable mechanical properties provides wide-ranging opportunities for applications in ion and molecular separations1, energy storage2 and electronics3. Because the performance of these applications relies heavily on the size of the nanopores, it is desirable to design and engineer with precision a suitable nanopore size with narrow size distributions. However, conventional top-down processes often yield log-normal distributions with long tails, particularly at the sub-nanometre scale4. Moreover, the size distribution and density of the nanopores are often intrinsically intercorrelated, leading to a trade-off between the two that substantially limits their applications5-9. Here we report a cascaded compression approach to narrowing the size distribution of nanopores with left skewness and ultrasmall tail deviation, while keeping the density of nanopores increasing at each compression cycle. The formation of nanopores is split into many small steps, in each of which the size distribution of all the existing nanopores is compressed by a combination of shrinkage and expansion and, at the same time as expansion, a new batch of nanopores is created, leading to increased nanopore density by each cycle. As a result, high-density nanopores in monolayer graphene with a left-skewed, short-tail size distribution are obtained that show ultrafast and ångström-size-tunable selective transport of ions and molecules, breaking the limitation of the conventional log-normal size distribution9,10. This method allows for independent control of several metrics of the generated nanopores, including the density, mean diameter, standard deviation and skewness of the size distribution, which will lead to the next leap in nanotechnology.

Domain-dependent strain and stacking in two-dimensional van der Waals ferroelectrics.

Van der Waals (vdW) ferroelectrics have attracted significant attention for their potential in next-generation nano-electronics. Two-dimensional (2D) group-IV monochalcogenides have emerged as a promising candidate due to their strong room temperature in-plane polarization down to a monolayer limit. However, their polarization is strongly coupled with the lattice strain and stacking orders, which impact their electronic properties. Here, we utilize four-dimensional scanning transmission electron microscopy (4D-STEM) to simultaneously probe the in-plane strain and out-of-plane stacking in vdW SnSe. Specifically, we observe large lattice strain up to 4% with a gradient across ~50 nm to compensate lattice mismatch at domain walls, mitigating defects initiation. Additionally, we discover the unusual ferroelectric-to-antiferroelectric domain walls stabilized by vdW force and may lead to anisotropic nonlinear optical responses. Our findings provide a comprehensive understanding of in-plane and out-of-plane structures affecting domain properties in vdW SnSe, laying the foundation for domain wall engineering in vdW ferroelectrics.

Angiotensin-I-Converting Enzyme (ACE)-Inhibitory Peptides from the Collagens of Monkfish (Lophius litulon) Swim Bladders: Isolation, Characterization, Molecular Docking Analysis and Activity Evaluation.

The objective of this study was to isolate and characterize collagen and angiotensin-I-converting enzyme (ACE)-inhibitory (ACEi) peptides from the swim bladders of monkfish (Lophius litulon). Therefore, acid-soluble collagen (ASC-M) and pepsin-soluble collagen (PSC-M) with yields of 4.27 ± 0.22% and 9.54 ± 0.51%, respectively, were extracted from monkfish swim bladders using acid and enzyme methods. The ASC-M and PSC-M contained Gly (325.2 and 314.9 residues/1000 residues, respectively) as the major amino acid, but they had low imino acid content (192.5 and 188.6 residues/1000 residues, respectively) in comparison with collagen from calf skins (CSC) (216.6 residues/1000 residues). The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) patterns and ultraviolet (UV) absorption spectrums of ASC-M and PSC-M illustrated that they were mainly composed of type I collagen. Subsequently, three ACEi peptides were isolated from a PSC-M hydrolysate prepared via a double-enzyme system (alcalase + neutrase) and identified as SEGPK (MHP6), FDGPY (MHP7) and SPGPW (MHP9), with molecular weights of 516.5, 597.6 and 542.6 Da, respectively. SEGPK, FDGPY and SPGPW displayed remarkable anti-ACE activity, with IC50 values of 0.63, 0.94 and 0.71 mg/mL, respectively. Additionally, a molecular docking assay demonstrated that the affinities of SEGPK, FDGPY and SPGPW with ACE were -7.3, -10.9 and -9.4 kcal/mol, respectively. The remarkable ACEi activity of SEGPK, FDGPY and SPGPW was due to their connection with the active pockets and/or sites of ACE via hydrogen bonding, hydrophobic interaction and electrostatic force. Moreover, SEGPK, FDGPY and SPGPW could protect HUVECs by controlling levels of nitric oxide (NO) and endothelin-1 (ET-1). Therefore, this work provides an effective means for the preparation of collagens and novel ACEi peptides from monkfish swim bladders, and the prepared ACEi peptides, including SEGPK, FDGPY and SPGPW, could serve as natural functional components in the development of health care products to control hypertension.

The intricate role of CCL5/CCR5 axis in Alzheimer disease.

The morbidity and mortality associated with Alzheimer disease (AD), one of the most common neurodegenerative diseases, are increasing each year. Although both amyloid ß and tau proteins are known to be involved in AD pathology, their detailed functions in the pathogenesis of the disease are not fully understood. There is increasing evidence that neuroinflammation contributes to the development and progression of AD, with astrocytes, microglia, and the cytokines and chemokines they secrete acting coordinately in these processes. Signaling involving chemokine (C-C motif) ligand 5 (CCL5) and its main receptor C-C chemokine receptor 5 (CCR5) plays an important role in normal physiologic processes as well as pathologic conditions such as neurodegeneration. In recent years, many studies have shown that the CCL5/CCR5 axis plays a major effect in the pathogenesis of AD, but there are also a few studies that contradict this. In short, the role of CCL5/CCR5 axis in the pathogenesis of AD is still intricate. This review summarizes the structure, distribution, physiologic functions of the CCL5/CCR5 axis, and the progress in understanding its involvement in the pathogenesis of AD.

NKRF in Cardiac Fibroblasts Protects against Cardiac Remodeling Post-Myocardial Infarction via Human Antigen R.

Myocardial infarction (MI) remains the leading cause of death worldwide. Cardiac fibroblasts (CFs) are abundant in the heart and are responsible for cardiac repair post-MI. NF-κB-repressing factor (NKRF) plays a significant role in the transcriptional inhibition of various specific genes. However, the NKRF action mechanism in CFs remains unclear in cardiac repair post-MI. This study investigates the NKRF mechanism in cardiac remodeling and dysfunction post-MI by establishing a CF-specific NKRF-knockout (NKRF-CKO) mouse model. NKRF expression is downregulated in CFs in response to pathological cardiac remodeling in vivo and TNF-α in vitro. NKRF-CKO mice demonstrate worse cardiac function and survival and increased infarct size, heart weight, and MMP2 and MMP9 expression post-MI compared with littermates. NKRF inhibits CF migration and invasion in vitro by downregulating MMP2 and MMP9 expression. Mechanistically, NKRF inhibits human antigen R (HuR) transcription by binding to the classical negative regulatory element within the HuR promoter via an NF-κB-dependent mechanism. This decreases HuR-targeted Mmp2 and Mmp9 mRNA stability. This study suggests that NKRF is a therapeutic target for pathological cardiac remodeling.

Giant room-temperature nonlinearities in a monolayer Janus topological semiconductor.

Nonlinear optical materials possess wide applications, ranging from terahertz and mid-infrared detection to energy harvesting. Recently, the correlations between nonlinear optical responses and certain topological properties, such as the Berry curvature and the quantum metric tensor, have attracted considerable interest. Here, we report giant room-temperature nonlinearities in non-centrosymmetric two-dimensional topological materials-the Janus transition metal dichalcogenides in the 1 T' phase, synthesized by an advanced atomic-layer substitution method. High harmonic generation, terahertz emission spectroscopy, and second harmonic generation measurements consistently show orders-of-the-magnitude enhancement in terahertz-frequency nonlinearities in 1 T' MoSSe (e.g., > 50 times higher than 2H MoS2 for 18th order harmonic generation; > 20 times higher than 2H MoS2 for terahertz emission). We link this giant nonlinear optical response to topological band mixing and strong inversion symmetry breaking due to the Janus structure. Our work defines general protocols for designing materials with large nonlinearities and heralds the applications of topological materials in optoelectronics down to the monolayer limit.