Direct radical functionalization of native sugars.

Naturally occurring (native) sugars and carbohydrates contain numerous hydroxyl groups of similar reactivity1,2. Chemists, therefore, rely typically on laborious, multi-step protecting-group strategies3 to convert these renewable feedstocks into reagents (glycosyl donors) to make glycans. The direct transformation of native sugars to complex saccharides remains a notable challenge. Here we describe a photoinduced approach to achieve site- and stereoselective chemical glycosylation from widely available native sugar building blocks, which through homolytic (one-electron) chemistry bypasses unnecessary hydroxyl group masking and manipulation. This process is reminiscent of nature in its regiocontrolled generation of a transient glycosyl donor, followed by radical-based cross-coupling with electrophiles on activation with light. Through selective anomeric functionalization of mono- and oligosaccharides, this protecting-group-free 'cap and glycosylate' approach offers straightforward access to a wide array of metabolically robust glycosyl compounds. Owing to its biocompatibility, the method was extended to the direct post-translational glycosylation of proteins.

Matrix viscoelasticity promotes liver cancer progression in the pre-cirrhotic liver.

Type 2 diabetes mellitus is a major risk factor for hepatocellular carcinoma (HCC). Changes in extracellular matrix (ECM) mechanics contribute to cancer development1,2, and increased stiffness is known to promote HCC progression in cirrhotic conditions3,4. Type 2 diabetes mellitus is characterized by an accumulation of advanced glycation end-products (AGEs) in the ECM; however, how this affects HCC in non-cirrhotic conditions is unclear. Here we find that, in patients and animal models, AGEs promote changes in collagen architecture and enhance ECM viscoelasticity, with greater viscous dissipation and faster stress relaxation, but not changes in stiffness. High AGEs and viscoelasticity combined with oncogenic ß-catenin signalling promote HCC induction, whereas inhibiting AGE production, reconstituting the AGE clearance receptor AGER1 or breaking AGE-mediated collagen cross-links reduces viscoelasticity and HCC growth. Matrix analysis and computational modelling demonstrate that lower interconnectivity of AGE-bundled collagen matrix, marked by shorter fibre length and greater heterogeneity, enhances viscoelasticity. Mechanistically, animal studies and 3D cell cultures show that enhanced viscoelasticity promotes HCC cell proliferation and invasion through an integrin-ß1-tensin-1-YAP mechanotransductive pathway. These results reveal that AGE-mediated structural changes enhance ECM viscoelasticity, and that viscoelasticity can promote cancer progression in vivo, independent of stiffness.

Milestones in understanding transport, sensing, and signaling of the plant nutrient phosphorus.

As an essential nutrient element, phosphorus (P) is primarily acquired and translocated as inorganic phosphate (Pi) by plant roots. Pi is often sequestered in the soil and becomes limited for plant growth. Plants have developed a sophisticated array of adaptive responses, termed P starvation responses, to cope with P deficiency by improving its external acquisition and internal utilization. Over the past 2 to 3 decades, remarkable progress has been made toward understanding how plants sense and respond to changing environmental P. This review provides an overview of the molecular mechanisms that regulate or coordinate P starvation responses, emphasizing P transport, sensing, and signaling. We present the major players and regulators responsible for Pi uptake and translocation. We then introduce how P is perceived at the root tip, how systemic P signaling is operated, and the mechanisms by which the intracellular P status is sensed and conveyed. Additionally, the recent exciting findings about the influence of P on plant-microbe interactions are highlighted. Finally, the challenges and prospects concerning the interplay between P and other nutrients and strategies to enhance P utilization efficiency are discussed. Insights obtained from this knowledge may guide future research endeavors in sustainable agriculture.

Heterozygous variants in USP25 cause genetic generalized epilepsy.

USP25 encodes ubiquitin-specific proteases 25, a key member of deubiquitinating enzyme family and is involved in neural fate determination. Although abnormal expression in Down's syndrome was reported previously, the specific role of USP25 in human diseases has not been defined. In this study, we performed trio-based whole exome sequencing in a cohort of 319 cases (families) with generalized epilepsy of unknown etiology. Five heterozygous USP25 variants including two de novo and three co-segregated variants were determined in eight individuals affected by generalized seizures and/or febrile seizures from five unrelated families. The frequency of USP25 variants showed a significantly high aggregation in this cohort compared to the East Asian population and all populations in the gnomAD database. The mean onset ages of febrile and afebrile seizures were 10 months (infancy) and 11.8 years (juvenile), respectively. The patients achieved seizure freedom except one had occasional nocturnal seizures at the last follow-up. Two patients exhibited intellectual disability. Usp25 was ubiquitously expressed in mouse brain with two peaks on embryonic days (E14‒E16) and postnatal day 21, respectively. Similarly, USP25 expressed in fetus/early childhood stage with a second peak at approximately 12‒20 years old in human brain, consistent with the seizure onset age at infancy and juvenile in the patients. To investigate the functional impact of USP25 deficiency in vivo, we established Usp25 knock-out mice, which showed increased seizure susceptibility compared to wild-type mice in pentylenetetrazol-induced seizure test. To explore the impact of USP25 variants, we employed multiple functional detections. In HEK293T cells, the severe phenotype associated variant (p.Gln889Ter) led to a significant reduction of mRNA and protein expressions but formed a stable truncated dimers with increment of deubiquitinating enzyme activities and abnormal cellular aggregations, indicating a gain-of-function effect. The p.Gln889Ter and p.Leu1045del increased neuronal excitability in mice brain, with a higher firing ability in p.Gln889Ter. These functional impairments align with the severity of the observed phenotypes, suggesting a genotype-phenotype correlation. Hence, a moderate association between USP25 and epilepsy was noted, indicating USP25 is potentially a predisposing gene for epilepsy. Our results from Usp25 null mice and the patient-derived variants indicated that USP25 would play epileptogenic role via loss-of-function or gain-of-function effects. The truncated variant p.Gln889Ter would have profoundly different effect on epilepsy. Together, our results underscore the significance of USP25 heterozygous variants in epilepsy, thereby highlighting the critical role of USP25 in the brain.

Human angiotensin-converting enzyme 2-specific antisense oligonucleotides reduce infection with SARS-CoV-2 variants.

BACKGROUND: The Spike protein mutation severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to decreased protective effect of various vaccines and mAbs, suggesting that blocking SARS-CoV-2 infection by targeting host factors would make the therapy more resilient against virus mutations. Angiotensin-converting enzyme 2 (ACE2) is the host receptor of SARS-CoV-2 and its variants, as well as many other coronaviruses. Downregulation of ACE2 expression in the respiratory tract may prevent viral infection. Antisense oligonucleotides (ASOs) can be rationally designed on the basis of sequence data, require no delivery system, and can be administered locally. OBJECTIVE: We sought to design ASOs that can block SARS-CoV-2 by downregulating ACE2 in human airway. METHODS: ACE2-targeting ASOs were designed using a bioinformatic method and screened in cell lines. Human primary nasal epithelial cells cultured at the air-liquid interface and humanized ACE2 mice were used to detect the ACE2 reduction levels and the safety of ASOs. ASO-pretreated nasal epithelial cells and mice were infected and then used to detect the viral infection levels. RESULTS: ASOs reduced ACE2 expression on mRNA and protein level in cell lines and in human nasal epithelial cells. Furthermore, they efficiently suppressed virus replication of 3 different SARS-CoV-2 variants in human nasal epithelial cells. In vivo, ASOs also downregulated human ACE2 in humanized ACE2 mice and thereby reduced viral load, histopathologic changes in lungs, and increased survival of mice. CONCLUSIONS: ACE2-targeting ASOs can effectively block SARS-CoV-2 infection. Our study provides a new approach for blocking SARS-CoV-2 and other ACE2-targeting virus in high-risk populations.

Wireless Photoactivated Targeted Nanosystem for Oncotherapy Via Synergistic Effects of Hyperthermia/Redox Stress Amplification/GSK-3ß Activity Inhibition.

Highly soluble salts and gas mediated therapies are emerging antitumor strategies. However, the therapeutic efficacy remains restricted by difficulty in delivering them to the tumor site and poorly controlled release in deep tissues. Here, an intelligent wireless photoactivated targeted nanosystem is designed for delivering LiCl and H2 to tumors for therapy. LiCl causes cell death by inhibiting the activity of GSK-3ß. H2 selectively interacts with reactive oxygen species in the tumor, leading to redox stress, which induces apoptosis. The significant heat generated by the nanosystem not only kills tumor cells but also accelerates the dissolution of LiCl and the release of H2. The rapid dissolution of LiCl leads to a surge in intracellular osmotic pressure, which further intensifies the redox stress response and enhances the efficiency of therapy. The nanosystem shows efficient tumor therapeutic capability via synergistic effects of hyperthermia/redox stress amplification/GSK-3ß activity inhibition.

Complement system is overactivated in patients with IgA nephropathy after COVID-19.

IgA nephropathy (IgAN), which has been confirmed as a complement mediated autoimmune disease, is also one form of glomerulonephritis associated with COVID-19. Here, we aim to investigate the clinical and immunological characteristics of patients with IgAN after COVID-19. The level of plasma level of C5a (p < 0.001), soluble C5b-9 (p = 0.018), FHR5 (p < 0.001) were all significantly higher in Group CoV (33 patients with renal biopsy-proven IgAN experienced COVID-19) compared with Group non-CoV (44 patients with IgAN without COVID-19), respectively. Compared with Group non-CoV, the intensity of glomerular C4d (p = 0.017) and MAC deposition (p < 0.001) and Gd-IgA1 deposition (p = 0.005) were much stronger in Group CoV. Our finding revealed that for IgAN after COVID-19, mucosal immune responses to SARS-CoV-2 infection may result in the overactivation of systemic and renal local complement system, and increased glomerular deposition of Gd-IgA1, which may lead to renal dysfunction and promote renal progression in IgAN patients.

Atomic Layer Deposition of TiO2 on Si Window Enables In Situ ATR-SEIRAS Measurements in Strong Alkaline Electrolytes.

The Si window is the most widely used internal reflection element (IRE) for electrochemical attenuated total reflection surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS), yet local chemical etching on Si by concentrated OH- anions bottlenecks the reliable application of this method in strong alkaline electrolytes. In this report, atomic layer deposition of a 25 nm nonconductive TiO2 barrier layer on the reflecting plane of a Si prism is demonstrated to address this challenge. In situ ATR-SEIRAS measurement on a Au film electrode with the Si/TiO2 composite IRE in 1 M NaOH reveals reversible global spectral features without spectral distortion at 1000-1300 cm-1, in stark contrast to those obtained with a bare Si window. By applying this structured ATR-SEIRAS, ethanol electrooxidation on a Pt/C catalyst in 1 and 5 M NaOH is explored, manifesting that such high pH values prevent the adsorption of as-formed acetate in the C2 pathway but not that of CO intermediate in the C1 pathway.

ABO and Rhesus blood groups and multiple health outcomes: an umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Numerous studies have been conducted to investigate the relationship between ABO and Rhesus (Rh) blood groups and various health outcomes. However, a comprehensive evaluation of the robustness of these associations is still lacking. METHODS: We searched PubMed, Web of Science, Embase, Scopus, Cochrane, and several regional databases from their inception until Feb 16, 2024, with the aim of identifying systematic reviews with meta-analyses of observational studies exploring associations between ABO and Rh blood groups and diverse health outcomes. For each association, we calculated the summary effect sizes, corresponding 95% confidence intervals, 95% prediction interval, heterogeneity, small-study effect, and evaluation of excess significance bias. The evidence was evaluated on a grading scale that ranged from convincing (Class I) to weak (Class IV). We assessed the certainty of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation criteria (GRADE). We also evaluated the methodological quality of included studies using the A Measurement Tool to Assess Systematic Reviews (AMSTAR). AMSTAR contains 11 items, which were scored as high (8-11), moderate (4-7), and low (0-3) quality. We have gotten the registration for protocol on the PROSPERO database (CRD42023409547). RESULTS: The current umbrella review included 51 systematic reviews with meta-analysis articles with 270 associations. We re-calculated each association and found only one convincing evidence (Class I) for an association between blood group B and type 2 diabetes mellitus risk compared with the non-B blood group. It had a summary odds ratio of 1.28 (95% confidence interval: 1.17, 1.40), was supported by 6870 cases with small heterogeneity (I2 = 13%) and 95% prediction intervals excluding the null value, and without hints of small-study effects (P for Egger's test > 0.10, but the largest study effect was not more conservative than the summary effect size) or excess of significance (P < 0.10, but the value of observed less than expected). And the article was demonstrated with high methodological quality using AMSTAR (score = 9). According to AMSTAR, 18, 32, and 11 studies were categorized as high, moderate, and low quality, respectively. Nine statistically significant associations reached moderate quality based on GRADE. CONCLUSIONS: Our findings suggest a potential relationship between ABO and Rh blood groups and adverse health outcomes. Particularly the association between blood group B and type 2 diabetes mellitus risk.

Encapsulating Bi Nanoparticles in Reduced Graphene Oxide with Strong Interfacial Bonding toward Advanced Potassium Storage.

Bismuth (Bi) is regarded as a promising anode material for potassium ion batteries (PIBs) due to its high theoretical capacity, but the huge volume expansion during potassiation and intrinsic low conductivity cause poor cycle stability and rate capability. Herein, a unique Bi nanoparticles/reduced graphene oxide (rGO) composite is fabricated by anchoring the Bi nanoparticles over the rGO substrate through a ball-milling and thermal reduction process. As depicted by the in-depth XPS analysis, strong interfacial Bi-C bonding can be formed between Bi and rGO, which is beneficial for alleviating the huge volume expansion of Bi during potassiation, restraining the aggregation of Bi nanoparticles and promoting the interfacial charge transfer. Theoretical calculation reveals the positive effect of rGO to enhance the potassium adsorption capability and interfacial electron transfer as well as reduce the diffusion energy barrier in the Bi/rGO composite. Thereby, the Bi/rGO composite exhibits excellent potassium storage performances in terms of high capacity (384.8 mAh g-1 at 50 mA g-1), excellent cycling stability (197.7 mAh g-1 after 1000 cycles at 500 mA g-1 with no capacity decay) and superior rate capability (55.6 mAh g-1 at 2 A g-1), demonstrating its great potential as an anode material for PIBs.

Manipulating Chiroptical Activities in 0D Chiral Hybrid Manganese Bromides by Solvent Molecular Engineering.

0D hybrid metal halides (0D HMHs) with fully isolated inorganic units provide an ideal platform for studying the correlations between chiroptical activities and crystal structures at atomic levels. Here, through the incorporation of different solvent molecules, a series of 0D chiral manganese bromides (RR/SS-C20H28N2)3MnBr8·2X (X = C2H5OH, CH3OH, or H2O) are synthesized to elucidate their chiroptical properties. They show negligible circular dichroism signals of Mn absorptions due to C2v-symmetric [MnBr4]2- tetrahedra. However, they display distinct circularly polarized luminescence (CPL) signals with continuously increased luminescence asymmetry factors (glum) from 10-4 (X = C2H5OH) to 10-3 (X = H2O). The increased glum value is structurally revealed to originate from the enhancement of [MnBr4]2- tetrahedral bond-angle distortions, due to the presence of different solvent molecules. Furthermore, (RR/SS-C20H28N2)MnBr4·H2O enantiomers with larger bond-angle distortions of [MnBr4]2- tetrahedra are synthesized based on hydrobromic acid-induced structural transformation of (RR/SS-C20H28N2)3MnBr8·2H2O enantiomers. Therefore, such (RR/SS-C20H28N2)MnBr4·H2O enantiomers exhibit enhanced CPL signals with |glum| up to 1.23 × 10-2. This work provides unique insight into enhancing chiroptical activities in 0D HMH systems.

Directed Self-Assembly of Polystyrene-Block-Polyhedral Oligomeric Silsesquioxane Monolayer by Nano-Trench for Nanopatterning.

This work pioneers to combine fast self-assembly of polyhedral oligomeric silsesquioxanes (POSS) nanocage-based giant surfactants with high etching contrast and directed self-assembly for reliable long-range lateral order to create well-aligned sub-10 nm line nanopatterns via reactive ion etching (RIE). Polystyrene-block-oligo(dimethylsiloxane) substituted POSS (PS-b-oDMS7POSS) with seven oligo(dimethylsiloxane) at the corners of the POSS nanocage and one polystyrene (PS) tail is designed and synthesized as a giant surfactant with self-assembly behaviors like block copolymer (BCP). In contrast to BCP, oDMS7POSS gives a volume-persistent "nanoatom" particle with higher mobility for fast self-assembly and higher segregation strength with PS for smaller feature size. By taking advantage of directed self-assembly using nano-trench fabricated by electron beam lithography, well-ordered nanostructured monolayer with well-aligned parallel oDMS7POSS cylinders can be formed by confined self-assembly within the nano-trench. With the optimization of the RIE treatment using O2 as an etchant, the high etching contrast from the oDMS7POSS and PS gives the formation of well-defined line nanopatterns with sub-10 nm critical dimension that can serve as a mask for pattern transfer in lithography. These results demonstrate a cost-effective approach for nanopatterning by utilizing a creatively designed giant surfactant with sub-10 nm feature size and excellent etching contrast for modern lithographic applications.

AZGP1 deficiency promotes angiogenesis in prostate cancer.

BACKGROUND: Loss of AZGP1 expression is a biomarker associated with progression to castration resistance, development of metastasis, and poor disease-specific survival in prostate cancer. However, high expression of AZGP1 cells in prostate cancer has been reported to increase proliferation and invasion. The exact role of AZGP1 in prostate cancer progression remains elusive. METHOD: AZGP1 knockout and overexpressing prostate cancer cells were generated using a lentiviral system. The effects of AZGP1 under- or over-expression in prostate cancer cells were evaluated by in vitro cell proliferation, migration, and invasion assays. Heterozygous AZGP1± mice were obtained from European Mouse Mutant Archive (EMMA), and prostate tissues from homozygous knockout male mice were collected at 2, 6 and 10 months for histological analysis. In vivo xenografts generated from AZGP1 under- or over-expressing prostate cancer cells were used to determine the role of AZGP1 in prostate cancer tumor growth, and subsequent proteomics analysis was conducted to elucidate the mechanisms of AZGP1 action in prostate cancer progression. AZGP1 expression and microvessel density were measured in human prostate cancer samples on a tissue microarray of 215 independent patient samples. RESULT: Neither the knockout nor overexpression of AZGP1 exhibited significant effects on prostate cancer cell proliferation, clonal growth, migration, or invasion in vitro. The prostates of AZGP1-/- mice initially appeared to have grossly normal morphology; however, we observed fibrosis in the periglandular stroma and higher blood vessel density in the mouse prostate by 6 months. In PC3 and DU145 mouse xenografts, over-expression of AZGP1 did not affect tumor growth. Instead, these tumors displayed decreased microvessel density compared to xenografts derived from PC3 and DU145 control cells, suggesting that AZGP1 functions to inhibit angiogenesis in prostate cancer. Proteomics profiling further indicated that, compared to control xenografts, AZGP1 overexpressing PC3 xenografts are enriched with angiogenesis pathway proteins, including YWHAZ, EPHA2, SERPINE1, and PDCD6, MMP9, GPX1, HSPB1, COL18A1, RNH1, and ANXA1. In vitro functional studies show that AZGP1 inhibits human umbilical vein endothelial cell proliferation, migration, tubular formation and branching. Additionally, tumor microarray analysis shows that AZGP1 expression is negatively correlated with blood vessel density in human prostate cancer tissues. CONCLUSION: AZGP1 is a negative regulator of angiogenesis, such that loss of AZGP1 promotes angiogenesis in prostate cancer. AZGP1 likely exerts heterotypical effects on cells in the tumor microenvironment, such as stromal and endothelial cells. This study sheds light on the anti-angiogenic characteristics of AZGP1 in the prostate and provides a rationale to target AZGP1 to inhibit prostate cancer progression.

Topological phases and non-Hermitian topology in tunable nonreciprocal cyclic three-mode optical systems.

We propose a method for simulating a 1D non-Hermitian Su-Schrieffer-Heeger model with modulated nonreciprocal hopping using a cyclic three-mode optical system. The current system exhibits different localization of topologically nontrivial phases, which can be characterized by the winding number. We find that the eigenenergies of such a system undergo a real-complex transition as the nonreciprocal hopping changes, accompanied by a non-Bloch parity-time symmetry breaking. We explain this phase transition by considering the evolution of saddle points on the complex energy plan and the ratio of complex eigenenergies. Additionally, we demonstrate that the skin states resulting from the non-Hermitian skin effect possess higher-order exceptional points under the critical point of the non-Bloch parity-time phase transition. Furthermore, we investigate the non-Hermitian skin phase transition by the directional mean inverse participation ratio and the generalized Brillouin zone. This work provides an alternative way to investigate the novel topological and non-Hermitian effects in nonreciprocal optical systems.

A developmental validation of the Quick TargSeq 1.0 integrated system for automated DNA genotyping in forensic science for reference samples.

Analysis of short tandem repeats (STRs) is a global standard method for human identification. Insertion/Deletion polymorphisms (DIPs) can be used for biogeographical ancestry inference. Current DNA typing involves a trained forensic worker operating several specialized instruments in a controlled laboratory environment, which takes 6-8 h. We developed the Quick TargSeq 1.0 integrated system (hereinafter abbreviated to Quick TargSeq) for automated generation of STR and DIP profiles from buccal swab samples and blood stains. The system fully integrates the processes of DNA extraction, polymerase chain reaction (PCR) amplification, and electrophoresis separation using microfluidic biochip technology. Internal validation studies were performed using RTyper 21 or DIP 38 chip cartridges with single-source reference samples according to the Scientific Working Group for DNA Analysis Methods guidelines. These results indicated that the Quick TargSeq system can process reference samples and generate STR or DIP profiles in approximately 2 h, and the profiles were concordant with those determined using traditional STR or DIP analysis methods. Thus, reproducible and concordant DNA profiles were obtained from reference samples. Throughout the study, no lane-to-lane or run-to-run contamination was observed. The Quick TargSeq system produced full profiles from buccal swabs with at least eight swipes, dried blood spot cards with two 2-mm disks, or 10 ng of purified DNA. Potential PCR inhibitors (i.e., coffee, smoking tobacco, and chewing tobacco) did not appear to affect the amplification reactions of the instrument. The overall success rate and concordance rate of 153 samples were 94.12% and 93.44%, respectively, which is comparable to other commercially available rapid DNA instruments. A blind test initiated by a DNA expert group showed that the system can correctly produce DNA profiles with 97.29% genotype concordance with standard bench-processing methods, and the profiles can be uploaded into the national DNA database. These results demonstrated that the Quick TargSeq system can rapidly generate reliable DNA profiles in an automated manner and has the potential for use in the field and forensic laboratories.

Triglyceride-glucose index and health outcomes: an umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Numerous meta-analyses have explored the association between the triglyceride-glucose (TyG) index and diverse health outcomes, yet the comprehensive assessment of the scope, validity, and quality of this evidence remains incomplete. Our aim was to systematically review and synthesise existing meta-analyses of TyG index and health outcomes and to assess the quality of the evidence. METHODS: A thorough search of PubMed, EMBASE, and Web of Science databases was conducted from their inception through to 8 April 2024. We assessed the quality of reviews using A Measurement Tool to Assess Systematic Reviews (AMSTAR) and the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. This study was registered with PROSPERO (CRD: 42024518587). RESULTS: Overall, a total of 95 associations from 29 meta-analyses were included, investigating associations between TyG index and 30 health outcomes. Of these, 83 (87.4%) associations were statistically significant (P < 0.05) according to the random effects model. Based on the AMSTAR tool, 16 (55.2%) meta-analyses were high quality and none was low quality. The certainty of the evidence, assessed by the GRADE framework, showed that 6 (6.3%) associations were supported by moderate-quality evidence. When compared with the lowest category of the TyG index, the risk of contrast-induced nephropathy (CIN) [relative risk (RR) = 2.25, 95%CI 1.82, 2.77], the risk of stroke in patients with diabetes mellitus (RR = 1.26, 95%CI 1.18, 1.33) or with acute coronary syndrome disease (RR = 1.56, 95%CI 1.06, 2.28), the prognosis of coronary artery disease (CAD)-non-fatal MI (RR = 2.02, 95%CI 1.32, 3.10), and the severity of CAD including coronary artery stenosis (RR = 3.49, 95%CI 1.71, 7.12) and multi-vessel CAD (RR = 2.33, 95%CI 1.59, 3.42) increased with high TyG index. CONCLUSION: We found that the TyG index was positively associated with many diseases including the risk of CIN and stroke, the prognosis of CAD, and the severity of CAD which were supported by moderate-quality evidence. TyG index might be useful to identify people at high-risk for developing these diseases.

Delta-sigma modulation supporting the 4194304QAM dual polarization signal at the W-band transmission over a 4.6†km wireless distance.

In this Letter, we propose a dual-polarized coherent millimeter-wave system based on differential delta-sigma modulation (D-DSM) intended for long-distance wireless transmission in the W-band. The proposed system can transmit polarization-division-multiplexed (PDM) D-DSM signals with modulation orders up to 4194304QAM over a wireless channel for 4.6 km at a signal baud rate of 20 G. After 4.6 km of wireless transmission, we successfully achieve a bit error rate (BER) lower than the hard-decision forward error correction (HD-FEC) of 3.8 × 10-3 for 34.51 Gbit/s PDM-524288QAM and a BER lower than the soft-decision forward error correction (SD-FEC) of 4.2 × 10-2 for 32.23 Gbit/s PDM-4194304QAM.

Digital mobile fronthaul scheme based on diff-delta-sigma modulation and OCT precoding.

In this Letter, we experimentally demonstrate digital mobile fronthaul (MFH) for 65536 quadrature amplitude modulation (65536-QAM) signals based on a diff-delta-sigma modulation (D-DSM) scheme with orthogonal circulant matrix transform (OCT) precoding. By combining the D-DSM scheme with OCT precoding, we successfully solved the problem of uneven distribution of in-band quantization noise (IBN) while bringing about a quantization SNR gain of about 1.5 dB. In addition, we compare two signal combination schemes, Gray coding and power superposition, in the D-DSM scheme. The results show that the power superposition scheme can achieve similar performance to Gray coding with lower computational complexity. At the same time, the power superposition scheme is less affected by the saturation effect. Therefore, the D-DSM solution combined with OCT precoding and power superposition provides an effective solution for future 6 G digital mobile fronthaul.

Giant strong coupling in a Q-BICs' tetramer metasurface.

Due to their ultrahigh Q-factor and small mode volume, bound states in the continuum (BICs) are intriguing for the fundamental study of the strong coupling regime. However, the strong coupling generated by BICs in one metasurface is not always strong enough, which highly limits its efficiency in applications. In this work, we realize a giant strong coupling of at most 60 meV in a quasi-BICs' (Q-BICs) tetramer metasurface composed of four Si cylinders with two different sets of diagonal lengths. The Q-BICs are induced from two types of electric quadrupole (EQ), for which detuning can be flexibly controlled by manipulating the C4v symmetry breaking Δd. The giant Rabi splitting in our proposed metasurface performs more than 15 times of the previous works, which provides more possibilities for important nonlinear and quantum applications, such as nanolaser and quantum optics.

Remimazolam Attenuates LPS-Derived Cognitive Dysfunction via Subdiaphragmatic Vagus Nerve Target α7nAChR-Mediated Nrf2/HO-1 Signal Pathway.

Sepsis-induced neuroinflammation is significantly associated with sepsis-related brain dysfunction. Remimazolam is a novel ultra-short-acting benzodiazepine anesthetic with multiple organ protective effects. However, it is unknown whether remimazolam can ameliorate LPS-induced brain impairment. In this study, Lipopolysaccharide (5 mg/kg, LPS) severely impaired Sprague-Dawley rats spatial learning ability, memory, and cognitive function. However, remimazolam treatment showed a protective effect on LPS-induced cognitive dysfunction. Remimazolam partly reversed LPS-induced splenomegaly, decreased serum cytokine expression, suppressed hippocampal M1 microglial activation, and mitigated oxidative stress injury and neuroinflammation. Electroacupuncture (EA) or PNU282987 treatment improved LPS-induced cognitive dysfunction and also significantly inhibited neuroinflammation and systemic inflammation. However, MLA, ML385, or subdiaphragmatic vagus nerve (SDV) treatment abolished the protective effects of remimazolam. Further mechanistic studies showed that remimazolam induces protective effects by activating subdiaphragmatic vagus nerve target α7nAChR-mediated Nrf2/HO-1 signaling pathway. These results demonstrate that remimazolam can up-regulate α7nAChR, Cyto-Nrf2, HO-1, and cognitive-related (CREB, BDNF, PSD95) protein expressions, suppress M1 microglia, ameliorate neuroinflammation or systemic inflammation, and reverse cognitive dysfunction. Therefore, this study provides insight into a new therapeutic target for the treatment of sepsis-induced cerebral dysfunction.