G protein-coupled estrogen receptor 1 ameliorates nonalcoholic steatohepatitis through targeting AMPK-dependent signaling.

Nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH), has emerged as a prevalent cause of liver cirrhosis and hepatocellular carcinoma, posing severe public health challenges worldwide. The incidence of NASH is highly correlated with an increased prevalence of obesity, insulin resistance, diabetes, and other metabolic diseases. Currently, no approved drugs specifically targeted for the therapies of NASH partially due to the unclear pathophysiological mechanisms. G protein-coupled estrogen receptor 1 (GPER1) is a membrane estrogen receptor involved in the development of metabolic diseases such as obesity and diabetes. However, the function of GPER1 in NAFLD/NASH progression remains unknown. Here, we show that GPER1 exerts a beneficial role in insulin resistance, hepatic lipid accumulation, oxidative stress, or inflammation in vivo and in vitro. In particular, we observed that the lipid accumulation, inflammatory response, fibrosis, or insulin resistance in mouse NAFLD/NASH models were exacerbated by hepatocyte-specific GPER1 knockout but obviously mitigated by hepatic GPER1 activation in female and male mice. Mechanistically, hepatic GPER1 activates AMP-activated protein kinase signaling by inducing cyclic AMP release, thereby exerting its protective effect. These data suggest that GPER1 may be a promising therapeutic target for NASH.

Orientation Sensitive SEIRA Sensors Based on Single-Walled Carbon Nanotube Near Fields.

Molecular vibrations that bear information about intrinsic properties of chemical compounds are challenging to detect at submonolayer densities. Surface-enhanced infrared absorption (SEIRA) spectroscopy has been proven to be a viable approach to enhance and detect weak vibration signals. Here, we report a SEIRA sensor based on mid-infrared surface plasmon resonances supported by single-walled carbon nanotubes (SWCNTs). Due to the 1D nature of SWCNTs, their plasmon modes are highly polarized with the electromagnetic fields spatially confined to nanometer scales. Leveraging these characteristics of SWCNTs, we observe a polarization selective coupling between their surface plasmons and vibrational modes of chemical bonds introduced onto their surfaces. A maximum modulation of ∼15% to the plasmon resonance peak is obtained for a submonolayer chemical group coverage. These findings suggest that SWCNTs may potentially serve as a highly sensitive SEIRA platform for revealing intricate information about molecular compositions and bond orientations.

Iridium-Catalyzed Enantioselective Transfer Hydrogenation of 1,1-Dialkylethenes with Ethanol: Scope and Mechanism.

Despite half a century's advance in the field of transition-metal-catalyzed asymmetric alkene hydrogenation, the enantioselective hydrogenation of purely alkyl-substituted 1,1-dialkylethenes has remained an unmet challenge. Herein, we describe a chiral PCNOx-pincer iridium complex for asymmetric transfer hydrogenation of this alkene class with ethanol, furnishing all-alkyl-substituted tertiary stereocenters. High levels of enantioselectivity can be achieved in the reactions of substrates with secondary/primary and primary/primary alkyl combinations. The catalyst is further applied to the redox isomerization of disubstituted alkenols, producing a tertiary stereocenter remote to the resulting carbonyl group. Mechanistic studies reveal a dihydride species, (PCNOx)Ir(H)2, as the catalytically active intermediate, which can decay to a dimeric species (κ3-PCNOx)IrH(µ-H)2IrH(κ2-PCNOx) via a ligand-remetalation pathway. The catalyst deactivation under the hydrogenation conditions with H2 is much faster than that under the transfer hydrogenation conditions with EtOH, which explains why the (PCNOx)Ir catalyst is effective for the transfer hydrogenation but ineffective for the hydrogenation. The suppression of di-to-trisubstituted alkene isomerization by regioselective 1,2-insertion is partly responsible for the success of this system, underscoring the critical role played by the pincer ligand in enantioselective transfer hydrogenation of 1,1-dialkylethenes. Moreover, computational studies elucidate the significant influence of the London dispersion interaction between the ligand and the substrate on enantioselectivity control, as illustrated by the complete reversal of stereochemistry through cyclohexyl-to-cyclopropyl group substitution in the alkene substrates.

Characterization of sub-nanosecond pulse compression based on frequency-detuning SBS.

High-frequency, high-power picosecond lasers have important and wide-ranging applications in laser ranging, optoelectronic countermeasures, and ultrafine industrial processing. Pulse compression based on stimulated Brillouin scattering (SBS) can achieve a highly efficient picosecond laser output, while improving the peak power and beam quality of the laser. In this paper, a generator-amplifier two-cell structure with frequency-detuning was proposed to achieve a pulse output that combines high compression ratio and high energy reflectivity. The experiment proved that under a pump pulse width of 15 ns and repetition frequency of 10 Hz, when the generator cell and amplifier cell media were selected as HT-230, the highest energy reflectivity of 46% and narrowest compression pulse width of 1.1 ns were achieved, and the pulse compression ratio was 13.6. When the amplifier cell was selected as FC-770 and the generator cell was selected as HT-230, an energy reflectivity of 52% and a compression pulse width of 840 ps could be achieved simultaneously, and the pulse compression ratio was 18.

High-power, gigahertz repetition frequency self-mode-locked Ho:GdVO4 laser resonantly pumped by a Tm-doped fiber laser.

A self-mode-locked Ho:GdVO4 laser with the GHz pulse repetition frequency oscillation near 2.06 µm was demonstrated for the first time to our knowledge. The output performances of the self-mode-locked Ho:GdVO4 laser were investigated for a few output coupler transmittances at the pulse repetition frequency of 1.89 GHz. At the incident pump power of 8.12 W, the maximum average output power was as high as 2.28 W, corresponding to the slope efficiency and optical-to-optical efficiency of 36.3% and 28.1%, respectively. This is the maximum average output for the 2 µm self-mode-locked solid-state laser with a GHz pulse repetition frequency. This work provides a new way for generating an efficient and a high-power ultrafast pulse laser with a GHz repetition frequency in the 2 µm wave band.

Self-healing propagation of a longitudinally varying vector optical beam for distance measurement.

Based on the longitudinal manipulation of polarization, a special vector optical beam (VOB) with customized polarization variation in propagation direction can be generated, whose properties and applications remain to be studied. Here, the self-healing propagation behaviors of the longitudinally varying VOB after an opaque object are investigated, and the localized polarization responses on the object distance are revealed. On this basis, characteristic parameters are defined to measure the distance of object, achieving a minimum relative error of 0.63% in a longitudinal range of 300 mm. Besides, the correlations and uncoupling methods of object distance and size are discussed. Our studies open new ways to use the structural properties of VOB and may be instructive for laser measurement.

High average output power, dual-wavelength synchronously self-mode-locked Ho:LLF laser operating at 2068.5 and 2069.2†nm.

A dual-wavelength synchronously self-mode-locked Ho:LLF laser operating at 2068.5 and 2069.2 nm was demonstrated. The maximum average output power was as high as 2.6 W with a pulse repetition frequency of 3.03 GHz. Meanwhile, the output power ratio of the dual-wavelength lasers can be effectively controlled by varying the incident pump power. To the best of our knowledge, this is the first dual-wavelength synchronously self-mode-locked Ho-doped fluoride solid state laser; moreover, our current experimental results represent the highest average output power from a GHz self-mode-locked oscillator in the 2 µm wave band.

HBCalculator: A Tool for Hydrogen Bond Distribution Calculations in Molecular Dynamics Simulations.

Hydrogen bonds, crucial noncovalent interactions in molecular systems, significantly impact biological, chemical, and energy-related processes; therefore, characterizing hydrogen bond information is of importance to fundamental studies. This work introduces the HBCalculator, a Tcl-based tool integrated with VMD for calculating 1D and 2D distributions of hydrogen bond density and strength. The tool facilitates spatial analysis, overcoming limitations in existing packages that lack direct spatial distribution output. By employing HBCalculator in MD simulations, three systems of cellulose/water and graphene/water interfaces, were tested to showcase its functionality. The 1D and 2D hydrogen bond distributions reveal insights into interfacial properties, reflecting the impact of material hydrophobicity. The simplicity of usage, along with its potential for diverse molecular systems, positions HBCalculator as a valuable tool for researchers exploring hydrogen bond networks.

Application of TiLOOP bra in implant-based breast reconstruction is associated with decreased complication risk compared with other meshes: A systematic review and meta-analysis.

BACKGROUND: TiLOOP bra has been used for over 15 years, however, evidence regarding its safety in implant-based breast reconstruction (IBBR) for patients with breast cancer after mastectomy is still limited. We performed this meta-analysis to evaluate its risks and benefits in IBBR comparing with other meshes. METHODS: Electronic databases were searched to identify relevant studies comparing postoperative complications between TiLOOP bra and other reconstruction techniques in IBBR with or without meshes. We also compared patient satisfaction in physical well-being between two groups. Risk ratios (RRs) and mean differences with 95% confidence interval (CI) were calculated. RESULTS: Seven studies representing 1203 cases were analyzed. Compared with other meshes, the use of TiLOOP bra significantly reduced the risk of infection (RR = 0.53, 95% CI, 0.32-0.86), seroma (RR = 0.21, 95% CI, 0.07-0.61), red breast syndrome (RR = 0.10, 95% CI, 0.02-0.45), and capsular contracture (RR = 0.20, 95% CI, 0.05-0.75). Patient satisfaction in physical well-being was comparable between two groups. CONCLUSIONS: TiLOOP bra in IBBR has a favored safety profile over other meshes, which significantly reduced postoperative complication risk and did not affect patient satisfaction. Although prospective well-designed controlled studies are still warranted, TiLOOP bra is safe and reliable at present.

Therapeutic and immune-regulation effects of Scutellaria baicalensis Georgi polysaccharide on pseudorabies in piglets.

Pseudorabies virus (PRV) can cause fatal encephalitis in newborn pigs and escape the immune system. While there is currently no effective treatment for PRV, Scutellaria baicalensis Georgi polysaccharides (SGP) and Rodgersia sambucifolia Hemsl flavonoids (RHF) are traditional Chinese herbal medicines with potential preventive and therapeutic effects against PRV infection. In order to explore which one is more effective in the prevention and treatment of PRV infection in piglets. We investigate the therapeutic effects of RHF and SGP in PRV-infected piglets using clinical symptom and pathological injury scoring systems. The immune regulatory effects of RHF and SGP on T lymphocyte transformation rate, cytokines, T cells, and Toll-like receptors were also measured to examine the molecular mechanisms of these effects. The results showed that SGP significantly reduced clinical symptoms and pathological damage in the lungs, liver, spleen, and kidneys in PRV-infected piglets and the T lymphocyte conversion rate in the SGP group was significantly higher than that in the other treatment groups, this potential dose-dependent effect of SGP on T lymphocyte conversation. Serum immunoglobulin and cytokine levels in the SGP group fluctuated during the treatment period, with SGP treatment showing better therapeutic and immunomodulatory effects in PRV-infected piglets than RHF or the combined SGP + RHF treatment. In conclusion, RHF and SGP treatments alleviate the clinical symptoms of PRV infection in piglets, and the immunomodulatory effect of SGP treatment was better than that of the RHF and a combination of both treatments. This study provides evidence for SGP in controlling PRV infection in piglets.

Risk of interstitial lung disease with the use of programmed cell death 1 (PD-1) inhibitor compared with programmed cell death ligand 1 (PD-L1) inhibitor in patients with breast cancer: A systematic review and meta-analysis.

Background: Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have become integral elements within the current landscape of breast cancer treatment modalities; however, they are associated with interstitial lung disease (ILD), which is rare but potentially fatal. Notably, only a few studies have compared the difference in ILD incidence between PD-1 and PD-L1 inhibitors. Therefore, this study aimed to assess the discrepancies regarding ILD risk between the two immune checkpoint inhibitors. We also reported three cases of ILD after PD-1 inhibitor treatment. Methods: We comprehensively searched PubMed, EMBASE, and the Cochrane Library to identify clinical trials that investigated PD-1/PD-L1 inhibitor treatment for patients with breast cancer. Pooled overall estimates of incidence and risk ratio (RR) were calculated with a 95% confidence interval (CI), and a mirror group analysis was performed using eligible studies. Results: This meta-analysis included 29 studies with 4639 patients who received PD-1/PD-L1 inhibitor treatment. A higher ILD incidence was observed among 2508 patients treated with PD-1 inhibitors than among 2131 patients treated with PD-L1 inhibitors (0.05 vs. 0.02). The mirror group analysis further revealed a higher ILD event risk in patients treated with PD-1 inhibitors than in those treated with PD-L1 inhibitors (RR = 2.34, 95% CI, 1.13-4.82, P = 0.02). Conclusion: Our findings suggest a greater risk of ILD with PD-1 inhibitors than with PD-L1 inhibitors. These findings are instrumental for clinicians in treatment deliberations, and the adoption of more structured diagnostic approaches and management protocols is necessary to mitigate the risk of ILD.

Development and biomechanical analysis of an axially controlled compression spinal rod for lumbar spondylolysis.

BACKGROUND: To elucidate the differences in mechanical performance between a novel axially controlled compression spinal rod (ACCSR) for lumbar spondylolysis (LS) and the common spinal rod (CSR). METHODS: A total of 36 ACCSRs and 36 CSRs from the same batch were used in this study, each with a diameter of 6.0 mm. Biomechanical tests were carried out on spinal rods for the ACCSR group and on pedicle screw-rod internal fixation systems for the CSR group. The spinal rod tests were conducted following the guidelines outlined in the American Society for Testing and Materials (ASTM) F 2193, while the pedicle screw-rod internal fixation system tests adhered to ASTM F 1798-97 standards. RESULTS: The stiffness of ACCSR and CSR was 1559.15 ±â€…50.15 and 3788.86 ±â€…156.45 N/mm (P < .001). ACCSR's yield load was 1345.73 (1297.90-1359.97) N, whereas CSR's was 4046.83 (3805.8-4072.53) N (P = .002). ACCSR's load in the 2.5 millionth cycle of the fatigue four-point bending test was 320 N. The axial gripping capacity of ACCSR and CSR was 1632.53 ±â€…165.64 and 1273.62 ±â€…205.63 N (P = .004). ACCSR's torsional gripping capacity was 3.45 (3.23-3.47) Nm, while CSR's was 3.27 (3.07-3.59) Nm (P = .654). The stiffness of the pedicle screws of the ACCSR and CSR group was 783.83 (775.67-798.94) and 773.14 (758.70-783.62) N/mm (P = .085). The yield loads on the pedicle screws of the ACCSR and CSR group was 1345.73 (1297.90-1359.97) and 4046.83 (3805.8-4072.53) N (P = .099). CONCLUSION: Although ACCSR exhibited lower yield load, stiffness, and fatigue resistance compared to CSR, it demonstrated significantly higher axial gripping capacity and met the stress requirement of the human isthmus. Consequently, ACCSR presents a promising alternative to CSR for LS remediation.