The IL-17 pathway intertwines with neurotrophin and TLR/IL-1R pathways since its domain shuffling origin.

The IL-17 pathway displays remarkably diverse functional modes between different subphyla, classes, and even orders, yet its driving factors remains elusive. Here, we demonstrate that the IL-17 pathway originated through domain shuffling between a Toll-like receptor (TLR)/IL-1R pathway and a neurotrophin-RTK (receptor-tyrosine-kinase) pathway (a Trunk-Torso pathway). Unlike other new pathways that evolve independently, the IL-17 pathway remains intertwined with its donor pathways throughout later evolution. This intertwining not only influenced the gains and losses of domains and components in the pathway but also drove the diversification of the pathway's functional modes among animal lineages. For instance, we reveal that the crustacean female sex hormone, a neurotrophin inducing sex differentiation, could interact with IL-17Rs and thus be classified as true IL-17s. Additionally, the insect prothoracicotropic hormone, a neurotrophin initiating ecdysis in Drosophila by binding to Torso, could bind to IL-17Rs in other insects. Furthermore, IL-17R and TLR/IL-1R pathways maintain crosstalk in amphioxus and zebrafish. Moreover, the loss of the Death domain in the pathway adaptor connection to IκB kinase and stress-activated protein kinase (CIKSs) dramatically reduced their abilities to activate nuclear factor-kappaB (NF-κB) and activator protein 1 (AP-1) in amphioxus and zebrafish. Reinstating this Death domain not only enhanced NF-κB/AP-1 activation but also strengthened anti-bacterial immunity in zebrafish larvae. This could explain why the mammalian IL-17 pathway, whose CIKS also lacks Death, is considered a weak signaling activator, relying on synergies with other pathways. Our findings provide insights into the functional diversity of the IL-17 pathway and unveil evolutionary principles that could govern the pathway and be used to redesign and manipulate it.

Differential roles of the fish chitinous membrane in gut barrier immunity and digestive compartments.

The chitin-based peritrophic matrix (PM) is a structure critical for both gut immunity and digestion in invertebrates. PM was traditionally considered lost in all vertebrates, but a PM-like chitinous membrane (CM) has recently been discovered in fishes, which may increase the knowledge on vertebrate gut physiology and structural evolution. Here, we show that in zebrafish, the CM affects ingestion behavior, microbial homeostasis, epithelial renewal, digestion, growth, and longevity. Young mutant fish without CM appear healthy and are able to complete their life cycle normally, but with increasing age they develop gut inflammation, resulting in gut atrophy. Unlike mammals, zebrafish have no visible gel-forming mucin layers to protect their gut epithelia, but at least in young fish, the CM is not a prerequisite for the antibacterial gut immunity. These findings provide new insights into the role of the CM in fish prosperity and its eventual loss in tetrapods. These findings may also help to improve fish health and conservation, as well as to advance the understanding of vertebrate gut physiology and human intestinal diseases.

Safety evaluation of single-sperm cryopreservation technique applied in intracytoplasmic sperm injection.

Intracytoplasmic sperm injection (ICSI) is a technique that directly injects a single sperm into the cytoplasm of mature oocytes. Here, we explored the safety of single-sperm cryopreservation applied in ICSI. This retrospective study enrolled 186 couples undergoing ICSI-assisted pregnancy. Subjects were allocated to the fresh sperm (group A)/single-sperm cryopreservation (group B) groups based on sperm type, with their clinical baseline/pathological data documented. We used ICSI-compliant sperm for subsequent in vitro fertilization and followed up on all subjects. The recovery rate/cryosurvival rate/sperm motility of both groups, the pregnancy/outcome of women receiving embryo transfer, and the delivery mode/neonatal-related information of women with successful deliveries were recorded. The clinical pregnancy rate, cumulative clinical pregnancy rate, abortion rate, ectopic pregnancy rate, premature delivery rate, live birth delivery rate, neonatal birth defect rate, and average birth weight were analyzed. The two groups showed no significant differences in age, body mass index, ovulation induction regimen, sex hormone [anti-Müllerian hormone (AMH)/follicle-stimulating hormone (FSH)/luteinizing hormone (LH)] levels, or oocyte retrieval cycles. The sperm recovery rate (51.72%-100.00%) and resuscitation rate (62.09% ± 16.67%) in group B were higher; the sperm motility in the two groups demonstrated no significant difference and met the ICSI requirements. Group B exhibited an increased fertilization rate, decreased abortion rate, and increased safety versus group A. Compared with fresh sperm, the application of single-sperm cryopreservation in ICSI sensibly improved the fertilization rate and reduced the abortion rate, showing higher safety.

SUMO and PIAS repress NF-κB activation in a basal chordate.

Small ubiquitin-like modifier (SUMO) regulates various biological processes, including the MyD88/TICAMs-IRAKs-TRAF6-NF-κB pathway, one of the core immune pathways. However, its functions are inconsistent between invertebrates and vertebrates and have rarely been investigated in lower chordates, including amphioxus and fishes. Here, we investigated the SUMOylation gene system in the amphioxus, a living basal chordate. We found that amphioxus has a SUMOylation system that has a complete set of genes and preserves several ancestral traits. We proceeded to study their molecular functions using the mammal cell lines. Both amphioxus SUMO1 and SUMO2 were shown to be able to attach to NF-κB Rel and to inhibit NF-κB activation by 50-75% in a dose-dependent fashion. The inhibition by SUMO2 could be further enhanced by the addition of the SUMO E2 ligase UBC9. In comparison, while human SUMO2 inhibited RelA, human SUMO1 slightly activated RelA. We also showed that, similar to human PIAS1-4, amphioxus PIAS could serve as a SUMO E3 ligase and promote its self-SUMOylation. This suggests that amphioxus PIAS is functionally compatible in human cells. Moreover, we showed that amphioxus PIAS is not only able to inhibit NF-κB activation induced by MyD88, TICAM-like, TRAF6 and IRAK4 but also able to suppress NF-κB Rel completely in the presence of SUMO1/2 in a dose-insensitive manner. This suggests that PIAS could effectively block Rel by promoting Rel SUMOylation. In comparison, in humans, only PIAS3, but not PIAS1/2/4, has been reported to promote NF-κB SUMOylation. Taken together, the findings from amphioxus, together with those from mammals and other species, not only offer insights into the functional volatility of the animal SUMO system, but also shed light on its evolutionary transitions from amphioxus to fish, and ultimately to humans.

The impact of non-adiabatic effects on reaction dynamics: a study based on the adiabatic and non-adiabatic potential energy surfaces of CaH2.

The two-state non-adiabatic potential energy matrices of the CaH2+ system are calculated via a diabatization approach by using a neural network model. Subsequently, the adiabatic and non-adiabatic potential energy surfaces (PESs) are constructed based on these non-adiabatic potential energy matrices. Furthermore, based on the adiabatic and non-adiabatic PESs, the Ca+(4s2S) + H2(X1Σ+g) → H(2S) + CaH+(X1Σ+) reaction is studied using the time-dependent wave packet method. Comparative analysis of the experimental and theoretical integral reaction cross-sections (ICSs) indicates that the maximum deviation between the results obtained from the adiabatic PES and the corresponding experimental value is 12.7 bohr2; in contrast, the maximum discrepancy between the theoretical result derived from the non-adiabatic PES and the experimental value is merely 0.42 bohr2. The potential well along the reaction path acts as a 'filter', selectively guiding intermediates with longer lifetimes in the potential well back to the reactant channel. This phenomenon indicates that the non-adiabatic effects significantly influence the reaction dynamics of the CaH2+ system.

Effect of intermolecular interaction of the charge-transfer complex between molecular "tweezers" and C60/C70 on second-order nonlinear optical properties.

To enhance understanding of the correlation between the intermolecular interaction and second-order nonlinear optical (NLO) properties, we studied a "molecular tweezer" with two corannulene substituents linked by a tetrahydro[5]helicene imide, which enabled highly sensitive and selective complexation of C60/C70 through convex-concave π-π interactions. The geometric structure, molecular orbitals, intermolecular interactions, electron absorption spectra and second-order NLO properties of the charge-transfer (CT) complexes formed by molecular tweezers and C60/C70 were studied by density functional theory. Larger fullerenes helped to increase the intermolecular interaction and CT, thereby increasing the first hyperpolarizabilities of CT complexes. Embedding of lithium ions helped to enhance the electron-absorption ability of fullerenes, thereby increasing the intermolecular interaction and intermolecular CT and, thus, enhancing their first hyperpolarizability significantly. Our data indicated that, through structure adjustment (including increasing the volume of fullerene and embedding alkali metal ions), we could enhance intermolecular interactions and improve intermolecular CT significantly. These actions could improve the second-order NLO properties of CT complexes.

Crystal structures of main proteases of SARS-CoV-2 variants bound to a benzothiazole-based inhibitor.

Main protease (M pro) serves as an indispensable factor in the life cycle of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as its constantly emerging variants and is therefore considered an attractive target for antiviral drug development. Benzothiazole-based inhibitors targeting M pro have recently been investigated by several groups and proven to be promising leads for coronaviral drug development. In the present study, we determine the crystal structures of a benzothiazole-based inhibitor, YH-53, bound to M pro mutants from SARS-CoV-2 variants of concern (VOCs) or variants of interest (VOIs), including K90R (Beta, B.1.351), G15S (Lambda, C.37), Y54C (Delta, AY.4), M49I (Omicron, BA.5) and P132H (Omicron, B.1.1.529). The structures show that the benzothiazole group in YH-53 forms a C-S covalent bond with the sulfur atom of catalytic residue Cys145 in SARS-CoV-2 M pro mutants. Structural analysis reveals the key molecular determinants necessary for interaction and illustrates the binding mode of YH-53 to these mutant M pros. In conclusion, structural insights from this study offer more information to develop benzothiazole-based drugs that are broader spectrum, more effective and safer.

Control one-dimensional length of rectangular pore on graphene membrane for better desalination performance.

At present, there is a general contradiction between permeability and selectivity of reverse osmosis (RO) membranes for desalination; a membrane with higher water permeability will give a lower salt rejection or selectivity, and vice versa. In this work, single-layer nanoporous graphene is used as RO membrane to investigate the effects of pore shape to reduce this contradiction by molecular dynamics simulations. Two kinds of pores (round and rectangular pores) with different sizes are simulated. For round pore, although the water permeability increases with the increase of the pore size, the salt rejection rate drops rapidly. For rectangular pore, reasonable designed pore structure can achieve improved water permeability and high salt rejection of graphene membrane by keeping one-dimensional length (i.e. the width) of the pore less than the size of the hydrated ions and increasing the other dimensional length. The restriction of one dimension can prevent the passage of hydrated ions through the pore effectively. This 'one-dimensional restriction' provides a simple strategy for designing RO membrane with variable pore structures to obtain a better desalination performance.

Functional Variation of IL-1R-Associated Kinases in the Conserved MyD88-TRAF6 Pathway during Evolution.

IL-1R-associated kinases (IRAK) are important regulators in the TLR/IL-1R pathways, but their function appears inconsistent between Drosophila, bony fishes, and vertebrates. This causes a difficulty to understand the IRAK functions. As a step to reveal the evolution of IRAKs, in this study, we performed comparative and functional analysis of IRAKs by exploiting the amphioxus, a pivotal taxon connecting invertebrates and vertebrates. Sequence and phylogenetic analysis indicated three major IRAK lineages: IRAK1/2/3 is a vertebrate-specific lineage, IRAK4 is an ancient lineage conserved between invertebrate and vertebrates, and Pelle is another ancient lineage that is preserved in protostomes and invertebrate deuterostomes but lost in vertebrate deuterostomes. Pelle is closer neither to IRAK4 nor to IRAK1/2/3, hence suggesting no clear functional analogs to IRAK1/2/3 in nonvertebrates. Functional analysis showed that both amphioxus IRAK4 and Pelle could suppress NF-κB activation induced by MyD88 and TRAF6, which are unlike mammalian and Drosophila IRAKs, but, surprisingly, similar to bony fish IRAK4. Also unlike Drosophila IRAKs, no interaction was detected between amphioxus IRAK4 and Pelle, although both of them were shown capable of binding MyD88. These findings, together with previous reports, show that unlike other signal transducers in the TLR/IL-1R pathways, such as MyD88 and TRAF6, the functions of IRAKs are highly variable during evolution and very specialized in different major animal taxa. Indeed, we suggest that the functional variability of IRAKs might confer plasticity to the signal transduction of the TLR/IL-1R pathways, which in return helps the species to evolve against the pathogens.

Assembling of Perylene, Naphthalene, and Pyromellitic Diimide-Based Materials and Their Third-Order Nonlinear Optical Properties.

π-conjugated aromatic diimides with chemical stability, heat resistance, and redox activity have attracted more attention due to their excellent fluorescence quantum yield in solution. The planar perylene diimide (PDI) derivatives generally have aggregation-induced emission quenching in the solid state, while the cyclic trimers based on pyromellitic diimides (PMDIs), naphthalene diimides (NDIs), and PDIs can increase the fluorescence quantum yield in the solid state and have large two-photon absorption cross section, which can be used as excellent nonlinear optical (NLO) materials. Therefore, this paper will study the effects of multiple assembly modes of the three monomers on the NLO responses of materials. It was found that the assembly modes of 2PMDI-1NDI and 2NDI-1PDI exhibit larger third-order NLO response (γ) values, which was due to the larger conjugate surface of PDI effectively reducing the energy gap between the HOMO and LUMO. Compared with other assembly methods, 2PMDI-1NDI and 2NDI-1PDI were conducive to causing redshifts (150 nm) in the absorption spectrum. Therefore, the larger conjugate surface of PDI and the assembly mode of the isosceles triangle were more favorable for intramolecular charge transfer, thus improving its NLO properties.

E2F1 promotes cell cycle progression by stabilizing spindle fiber in colorectal cancer cells.

BACKGROUND: E2F1 is a transcription factor that regulates cell cycle progression. It is highly expressed in most cancer cells and activates transcription of cell cycle-related kinases. Stathmin1 and transforming acidic coiled-coil-containing protein 3 (TACC3) are factors that enhance the stability of spindle fiber. METHODS: The E2F1-mediated transcription of transforming acidic coiled-coil-containing protein 3 (TACC3) and stathmin1 was examined using the Cancer Genome Atlas (TCGA) analysis, quantitative polymerase chain reaction (qPCR), immunoblotting, chromatin immunoprecipitation (ChIP), and luciferase reporter. Protein-protein interaction was studied using co-IP. The spindle structure was shown by immunofluorescence. Phenotype experiments were performed through MTS assay, flow cytometry, and tumor xenografts. Clinical colorectal cancer (CRC) specimens were analyzed based on immunohistochemistry. RESULTS: The present study showed that E2F1 expression correlates positively with the expression levels of stathmin1 and TACC3 in colorectal cancer (CRC) tissues, and that E2F1 transactivates stathmin1 and TACC3 in CRC cells. Furthermore, protein kinase A (PKA)-mediated phosphorylation of stathmin1 at Ser16 is essential to the phosphorylation of TACC3 at Ser558, facilitating the assembly of TACC3/clathrin/α-tubulin complexes during spindle formation. Overexpression of Ser16-mutated stathmin1, as well as knockdown of stathmin1 or TACC3, lead to ectopic spindle poles including disorganized and multipolar spindles. Overexpression of wild-type but not Ser16-mutated stathmin1 promotes cell proliferation in vitro and tumor growth in vivo. Consistently, a high level of E2F1, stathmin1, or TACC3 not only associates with tumor size, lymph node metastasis, TNM stage, and distant metastasis, but predicts poor survival in CRC patients. CONCLUSIONS: E2F1 drives the cell cycle of CRC by promoting spindle assembly, in which E2F1-induced stathmin1 and TACC3 enhance the stability of spindle fiber.

[Xianfang Huoming Decoction improves sperm quality in asthenospermia mice: An investigation based on the detoxification and sperm-nourishing method].

OBJECTIVE: To investigate the mechanism of Xianfang Huoming Decoction (XHD) improving sperm motility in mice with asthenospermia (AS). METHODS: Thirty normal BALB/c mice were randomly divided into six groups, blank control, AS model control, low-dose XHD, medium-dose XHD, high-dose XHD and levocarnitine + vitamin E (LC+VE). The AS model was established in the latter five groups by injection of methotrexate at 0.5 mg/kg once a week, and the mice in the blank control group were injected with the same volume of normal saline, all for 8 weeks. From the ninth week, the animals in the blank control and AS model control groups were treated with PBS at 0.1 ml/d, those in the low-, medium- and high-dose XHD groups with XHD at 7.13, 14,2 and 28.52 g/kg/ d respectively, and those in the LC+VE group with LC+VE (30:1) at 0.55 g/kg/d, all for 4 weeks. Then, the bilateral epididymides were harvested from all the mice for preparation of a sperm suspension and observation of the total numbers of sperm and motile sperm. The testis tissues were obtained for to determination of the expressions of Nrf-2- and HO-1-related mRNA and proteins by fluorescence staining, RT-PCR and Western blot. RESULTS: Compared with the AS model controls, the mice treated with low-, medium- and high-dose XHD showed dramatically increased sperm concentration (ï¼»22.36 ± 16.02ï¼½ vs ï¼»39.04 ± 4.50ï¼½, ï¼»40.76 ± 6.57ï¼½ and ï¼»41.04 ± 8.39ï¼½ ×106/ml, P < 0.01) and motility (ï¼»22.89 ± 14.96ï¼½% vs ï¼»47.98 ± 4.74ï¼½%, ï¼»48.53 ± 6.03ï¼½% and ï¼»49.31 ± 6.24ï¼½%, P< 0.01), decreased level of reactive oxygen species (ROS) (ï¼»16.82 ± 14.96ï¼½% vs ï¼»12.08 ± 3.26ï¼½%, ï¼»10.77 ± 2.21ï¼½% and ï¼»9.56 ± 2.08ï¼½%, P< 0.01), and up-regulated expressions of Nrf-2- and HO-1-related mRNA and proteins in the testis tissue (P < 0.05 or P < 0.01). CONCLUSION: Xianfang Huoming Decoction inhibits the development of oxidative stress by up-regulating the expressions of Nrf-2- and HO-1-related mRNA and proteins in the testis tissue, which has provided theoretical evidence for its clinical application in the treatment of asthenospermia.

Broad distribution, high diversity and ancient origin of the ApeC-containing proteins.

Apextrin C-terminal (ApeC) is a novel protein domain with unknown functions, although early studies suggest that some ApeC-containing proteins (ACPs) bind to carbohydrates and have a role in development and immunity. Here we investigated the taxonomic distribution, sequence diversification and origin of ACPs in Metazoa. Most ACPs are present in invertebrates from aquatic or moist environments, including cnidarians, mollusks, echinoderms, cephalochordates, flatworms, water bears, nematodes and annelids. However, ACPs are absent in vertebrates and in most arthropod lineages (e.g. insects and crustaceans) except arachnids. ACPs apparently undergo rapid turnover and diversification, hence no orthologs could be found between (sub)phyla. ApeC can function either as a standalone domain or as a partner domain. It has been found to pair up with over ten different domain types in different ACPs. The partner domains are related to immunity, extracellular matrix, protein-protein and protein-carbohydrate interactions. Notably, the domain pair with the widest taxonomic distribution is MACPF/perforin-ApeC, which represent a classic group of ACPs called apextrins. ApeC also frequently pairs up with itself to form dual-ApeC modules in different phyla. Notably, in parasite flatworms, dual-ApeCs are present in 70% of ACPs and all inherited from a common ancestor. The broad distribution of MACPF-ApeC and dual-ApeC suggest their conserved yet unknown functions. We also discovered distant ApeC homologs in bacteria, hence tracing the origin of ApeC back to prokaryotes. Our findings show that ApeC has an ancient origin and is able to function alone or in complex domain architectures, though it is less prevalent than other versatile domains such as immunoglobulin domains and C-type lectin domains. This work provides a foundation for further functional study of this novel domain type.

Bidirectional planar-displacement waveguide tracker for high-concentration photovoltaics.

A bidirectional planar-displacement waveguide tracker was devised to replace the traditional two-axis tracking system for high-concentration photovoltaics, with improved module thickness, optical field uniformity, and current matching. The concentrating magnification reaches 725 times, and the sun tracking angle is more than 170°, which is equivalent to 11.3 tracking hours per day. The module thickness is only 6.16 cm. This design enabled us to place the module flat on the ground, in which swing was not required. This will greatly improve the mechanical strength and the lifetime of the module and solve the development dilemma faced by III-V multijunction solar cells.

Leukocyte cell-derived chemotaxin 2 promotes the development of nonalcoholic fatty liver disease through STAT-1 pathway in mice.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD), whose pathogenesis remains unelucidated, has become an increasingly prevalent disease globally requiring novel treatment strategies. This study aims to explore the role of leukocyte cell-derived chemotaxin 2 (LECT2), one of the known hepatokines, in the development of NAFLD. METHODS: The serum LECT2 level was evaluated in patients with NAFLD and male C57BL/6 mice fed a high-fat diet (HFD) for 8 weeks. Tail intravenous injection of adeno-associated virus that contained Lect2 short hairpin RNA or Lect2 overexpression plasmid was administered to mice to inhibit or increase hepatic Lect2 expression. Hepatic steatosis was evaluated by histological staining with haematoxylin and eosin and Oil Red O, and also by quantitative hepatic triglyceride measurements. RNA-seq was performed to discover the specific targets of LECT2 on NAFLD. RESULTS: Serum and hepatic LECT2 levels were elevated in NAFLD patients and HFD-fed mice. Inhibition of hepatic Lect2 expression alleviated HFD-induced hepatic steatosis and inflammation, whereas hepatic overexpression of Lect2 aggravated HFD-induced hepatic steatosis and inflammation. RNA-seq and bioinformatical analysis suggested that the signal transducers and activators of transcription-1 (STAT-1) pathway might play an indispensable role in the interaction between LECT2 and NAFLD. A STAT-1 inhibitor could reverse the accumulation of hepatic lipids caused by Lect2 overexpression. CONCLUSION: LECT2 expression is significantly elevated in NAFLD. LECT2 induces the occurrence and development of NAFLD through the STAT-1 pathway. LECT2 may be a potential therapeutic target for NAFLD.

Improvement of interfacial contact for efficient PCBM/MAPbI3planar heterojunction solar cells with a binary antisolvent mixture treatment.

Atomic-force microscopic images, x-ray diffraction patterns, Urbach energies and photoluminescence quenching experiments show that the interfacial contact quality between the hydrophobic [6,6]-phenyl-C61-buttric acid methyl ester (PCBM) thin film and hydrophilic CH3NH3PbI3(MAPbI3) thin film can be effectively improved by using a binary antisolvent mixture (toluene:dichloromethane or chlorobenzene:dichloromethane) in the anti-solvent mixture-mediated nucleation process, which increases the averaged power conversion efficiency of the resultant PEDOT:PSS (P3CT-Na) thin film based MAPbI3solar cells from 13.18% (18.52%) to 13.80% (19.55%). Beside, the use of 10% dichloromethane (DCM) in the binary antisolvent mixture results in a nano-textured MAPbI3thin film with multicrystalline micrometer-sized grains and thereby increasing the short-circuit current density and fill factor (FF) of the resultant solar cells. It is noted that a remarkable FF of 80.33% is achieved, which can be used to explain the stable photovoltaic performance without additional encapsulations.

Efficiency improvement of P3CT-Na based MAPbI3solar cells with a simple wetting process.

The averaged power conversion efficiency of polyelectrolytes (P3CT-Na) based MAPbI3solar cells can be increased from 14.94% to 17.46% with a wetting method before the spin-coating process of MAPbI3precursor solutions. The effects of the wetting process on the surface, structural, optical and excitonic properties of MAPbI3thin films are investigated by using the atomic-force microscopic images, x-ray diffraction patterns, transmittance spectra, photoluminescence spectra and Raman scattering spectra. The experimental results show that the wetting process of MAPbI3precursor solution on top of the P3CT-Na/ITO/glass substrate can be used to manipulate the molecular packing structure of the P3CT-Na thin film, which determines the formation of MAPbI3thin films.

The shape selectivity of corannulene dimers based on concave-convex and convex-convex shape complementarity as hosts for C60 and C70.

In the formation of noncovalent complexes, the stacking arrangements of corannulene and fullerene are diverse, most of which are combinations of multiple corannulenes and fullerene. Here, a composition ratio of 2 : 1 was selected for the complex between corannulene and fullerene (C60 and C70) to investigate the effects of different superposition modes, including concave-convex and convex-convex interactions, on the stability and third-order nonlinear optical (NLO) properties of the composite materials. It was found that the concave-convex interaction was stronger and it was reported to stabilize the charge-transfer (CT) complex more effectively than the convex-convex interaction. The dispersion range of the concave-convex interaction was larger than that of the convex-convex interaction, which is consistent with the interaction energy results. The packing design with the double convex-convex interactions exhibited the largest linear optical response and third-order NLO response, which showed that the convex-convex interaction was more likely to be excited and cause intermolecular CT as compared to the concave-convex interaction. This work confirmed that the packing arrangement significantly affected the NLO response and will advance the development of NLO crystals.

Associations of acrylamide with non-alcoholic fatty liver disease in American adults: a nationwide cross-sectional study.

BACKGROUND: Acrylamide (AA) is a toxicant to humans, but the association between AA exposure and the risk of non-alcoholic fatty liver disease (NAFLD) remains unclear. In this study, our objective is to examine the cross-sectional association between AA exposure and the risk of NAFLD in American adults. METHODS: A total of 3234 individuals who took part in the National Health and Nutrition Examination Survey (NHANES) 2003-2006 and 2013-2016 were enrolled in the study. NAFLD was diagnosed by the U.S. Fatty Liver Index. Multivariable logistic regression models were applied to estimate the association between AA and NAFLD in the whole group and the non-smoking group. RESULTS: We discovered that in the whole group, serum hemoglobin adducts of AA (HbAA) were negatively associated with the prevalence of NAFLD after adjustment for various covariables (P for trend < 0.001). Compared with individuals in the lowest HbAA quartiles, the odds ratios (ORs) with 95% confidence intervals (CIs) in the highest HbAA quartiles were 0.61 (0.46-0.81) and 0.57 (0.36-0.88) in the whole group and the non-smoking group, respectively. In contrast, HbGA/HbAA showed a significantly positive correlation with the prevalence of NAFLD in both groups (P for trend < 0.001). In addition, HbGA was not significantly associated with NAFLD in the whole group or the non-smoking group. CONCLUSIONS: HbAA is negatively associated with NAFLD whereas HbGA/HbAA is positively associated with NAFLD in adults in the U.S. Further studies are needed to clarify these relationships.

Light-to-Moderate Alcohol Consumption Is Associated With Increased Risk of Type 2 Diabetes in Individuals With Nonalcoholic Fatty Liver Disease: A Nine-Year Cohort Study.

OBJECTIVE: This study explored the association between light-to-moderate alcohol consumption (LMAC) and risk of type 2 diabetes mellitus (T2DM) in individuals with nonalcoholic fatty liver disease (NAFLD). METHODS: A 9-year cohort study was performed among Chinese men who underwent their annual health checkups between 2009 and 2018. NAFLD was diagnosed based on abdominal ultrasound with exclusion of excess alcohol intake and other causes of liver disease. Logistic regression and Cox proportional regression analyses were applied to identify the risk of prevalent and incident T2DM. RESULTS: Of the 7,079 participants enrolled, 243 had T2DM at baseline and 630 developed T2DM during the 45,456 person-years follow-up. Both at the baseline and by the end of the follow-up, LMAC was associated with a decreased risk of prevalent T2DM in NAFLD-free participants but with a significantly increased risk in patients with NAFLD. LMAC was also associated with a decreased risk of incident T2DM in NAFLD-free participants. The adjusted hazard ratios (95% confidence interval) of incident T2DM were 0.224 (0.115-0.437) and 0.464 (0.303-0.710) for NAFLD-free light drinkers and NAFLD-free moderate drinkers, respectively. Nondrinking, light-drinking, and moderate-drinking patients with NAFLD all showed significantly increased risks of incident T2DM. Compared with NAFLD-free nondrinkers, the adjusted hazard ratios (95% confidence interval) of incident T2DM were 1.672 (1.336-2.092), 2.642 (1.958-3.565), and 2.687 (2.106-3.427) for nondrinking, light-drinking, and moderate-drinking patients with NAFLD, respectively. DISCUSSION: LMAC decreased the risks of prevalent and incident T2DM in NAFLD-free participants. LMAC, however, was associated with an increased risk of T2DM in patients with NAFLD (ClinicalTrials.gov number: NCT03847116).