Liver stiffness in hepatocellular carcinoma and chronic hepatitis patients: Hepatitis B virus infection and transaminases should be considered.

BACKGROUND: Liver condition is a crucial prognostic factor for patients with hepatocellular carcinoma (HCC), but a convenient and comprehensive method to assess liver condition is lacking. Liver stiffness (LS) measured by two-dimensional shear wave elastography may help in assessing liver fibrosis and liver condition. Chronic hepatitis B (CHB) is an important risk factor for HCC progression, but LS was found to be less reliable in assessing liver fibrosis following hepatitis viral eradication. We hypothesize that the status of hepatitis virus infection would affect the accuracy of LS in assessing the liver condition. AIM: To test the feasibility and impact factors of using LS to assess liver condition in patients with HCC and CHB. METHODS: A total of 284 patients were retrospectively recruited and classified into two groups on the basis of serum CHB virus hepatitis B virus (HBV)-DNA levels [HBV-DNA ≥ 100.00 IU/mL as Pos group (n = 200) and < 100.00 IU/mL as Neg group (n = 84)]. Correlation analyses and receiver operating characteristic analyses were conducted to evaluate the relationship between LS and liver condition. RESULTS: A significant correlation was found between LS and most of the parameters considered to have the ability to evaluate liver condition (P < 0.05). When alanine aminotransferase (ALT) concentrations were normal (≤ 40 U/L), LS was correlated with liver condition indices (P < 0.05), but the optimal cutoff of LS to identify a Child-Pugh score of 5 was higher in the Neg group (9.30 kPa) than the Pos group (7.40 kPa). When ALT levels were elevated (> 40 U/L), the correlations between LS and liver condition indices were not significant (P > 0.05). CONCLUSION: LS was significantly correlated with most liver condition indices in patients with CHB and HCC. However, these correlations varied according to differences in HBV-DNA and transaminase concentrations.

The association of haemoglobin A1c variability with adverse outcomes in patients with atrial fibrillation prescribed anticoagulants.

AIMS: The association of haemoglobin A1c (HbA1c) variability with the risk of adverse outcomes in patients with atrial fibrillation (AF) prescribed anticoagulants remains unclear. This study aimed to evaluate the association of HbA1c variability with the risk of ischaemic stroke (IS)/systemic embolism (SE) and all-cause mortality among patients with non-valvular AF prescribed anticoagulants. METHODS AND RESULTS: Patients newly diagnosed with AF from 2013 to 2018 were included. Variability in HbA1c, indexed by the coefficient of variation (CV), was determined for those with at least three HbA1c measurements available from the time of study enrolment to the end of follow-up. To evaluate whether prevalent diabetes would modify the relationship between HbA1c variability and outcomes, participants were divided into diabetes and non-diabetes groups. The study included 8790 patients (mean age 72.7% and 48.5% female). Over a median follow-up of 5.5 years (interquartile range 5.2, 5.8), the incident rate was 3.74 per 100 person-years for IS/SE and 4.89 for all-cause mortality in the diabetes group. The corresponding incident rates in the non-diabetes group were 2.41 and 2.42 per 100 person-years. In the diabetes group, after adjusting for covariates including mean HbA1c, greater HbA1c variability was significantly associated with increased risk of IS/SE [hazard ratio (HR) = 1.65, 95% confidence interval (CI): 1.27-2.13) and all-cause mortality (HR = 1.24, 95% CI: 1.05-1.47) compared with the lowest CV tertile. A similar pattern was evident in the non-diabetes group (IS/SE: HR = 1.58, 95% CI: 1.23-2.02; all-cause mortality: HR = 1.35, 95% CI: 1.10-1.64). CONCLUSION: Greater HbA1c variability was independently associated with increased risk of IS/SE and all-cause mortality among patients with AF, regardless of diabetic status.

In patients with atrial fibrillation (AF), greater haemoglobin A1c (HbA1c) variability was independently associated with increased risk of ischaemic stroke/systemic embolism and all-cause mortality, regardless of diabetic status. The usefulness of HbA1c variability as a risk predictor is significant and could be integrated into the stratification of patients with AF. Even if HbA1c measurements are within standard guideline limits, patients with larger fluctuations in HbA1c level may be at higher risk of thromboembolism and death than patients with more stable HbA1c level.

Optimized inhaled LNP formulation for enhanced treatment of idiopathic pulmonary fibrosis via mRNA-mediated antibody therapy.

Lipid nanoparticle-assisted mRNA inhalation therapy necessitates addressing challenges such as resistance to shear force damage, mucus penetration, cellular internalization, rapid lysosomal escape, and target protein expression. Here, we introduce the innovative "LOOP" platform with a four-step workflow to develop inhaled lipid nanoparticles specifically for pulmonary mRNA delivery. iLNP-HP08LOOP featuring a high helper lipid ratio, acidic dialysis buffer, and excipient-assisted nebulization buffer, demonstrates exceptional stability and enhanced mRNA expression in the lungs. By incorporating mRNA encoding IL-11 single chain fragment variable (scFv), scFv@iLNP-HP08LOOP effectively delivers and secretes IL-11 scFv to the lungs of male mice, significantly inhibiting fibrosis. This formulation surpasses both inhaled and intravenously injected IL-11 scFv in inhibiting fibroblast activation and extracellular matrix deposition. The HP08LOOP system is also compatible with commercially available ALC0315 LNPs. Thus, the "LOOP" method presents a powerful platform for developing inhaled mRNA nanotherapeutics with potential for treating various respiratory diseases, including idiopathic pulmonary fibrosis.

High cardiovascular mortality risk among older merkel cell carcinoma patients.

OBJECTIVE: Previous research has primarily focused on the incidence and mortality rates of Merkel cell carcinoma (MCC), neglecting the examination of cardiovascular mortality (CVM) risk among survivors, particularly older patients. This study aims to assess the risk of CVM in older individuals diagnosed with MCC. METHODS: Data pertaining to older MCC patients were obtained from the Surveillance, Epidemiology, and End Results database (SEER). CVM risk was measured using standardized mortality ratio (SMR) and cumulative mortality. Multivariate Fine-Gray's competing risk model was utilized to evaluate the risk factors contributing to CVM. RESULTS: Among the study population of 2,899 MCC patients, 465 (16.0%) experienced CVM during the follow-up period. With the prolongation of the follow-up duration, the cumulative mortality rate for CVM reached 27.36%, indicating that cardiovascular disease (CVD) became the second most common cause of death. MCC patients exhibited a higher CVM risk compared to the general population (SMR: 1.69; 95% CI: 1.54-1.86, p < 0.05). Notably, the SMR for other diseases of arteries, arterioles, and capillaries displayed the most significant elevation (SMR: 2.69; 95% CI: 1.16-5.29, p < 0.05). Furthermore, age at diagnosis and disease stage were identified as primary risk factors for CVM, whereas undergoing chemotherapy or radiation demonstrated a protective effect. CONCLUSION: This study emphasizes the significance of CVM as a competing cause of death in older individuals with MCC. MCC patients face a heightened risk of CVM compared to the general population. It is crucial to prioritize cardiovascular health starting from the time of diagnosis and implement personalized CVD monitoring and supportive interventions for MCC patients at high risk. These measures are essential for enhancing survival outcomes.

Integration of Plasmonic Ag(I) Clusters and Fe(II) Porphyrinates into Metal-Organic Frameworks for Efficient Photocatalytic CO2 Reduction Coupling with Photosynthesis of Pure H2O2.

Efficient photocatalytic CO2 reduction coupled with the photosynthesis of pure H2O2 is a challenging and significant task. Herein, using classical CO2 photoreduction site iron porphyrinate as the linker, Ag(I) clusters were spatially separated and evenly distributed within a new metal-organic framework (MOF), namely Ag27TPyP-Fe. With water as electron donors, Ag27TPyP-Fe exhibited remarkable performances in artificial photosynthetic overall reaction with CO yield of 36.5 µmol g-1 h-1 and ca. 100% selectivity, as well as H2O2 evolution rate of 35.9 µmol g-1 h-1. Since H2O2 in the liquid phase can be more readily separated from the gaseous products of CO2 photoreduction, high-purity H2O2 with a concentration up to 0.1 mM was obtained. Confirmed by theoretical calculations and the established energy level diagram, the reductive iron(II) porphyrinates and oxidative Ag(I) clusters within an integrated framework functioned synergistically to achieve artificial photosynthesis. Furthermore, photoluminescence spectroscopy and photoelectrochemical measurements revealed that the robust connection of Ag(I) clusters and iron porphyrinate ligands facilitated efficient charge separation and rapid electron transfer, thereby enhancing the photocatalytic activity.

Free Androgen Index Might Not Be a Perfect Predictor of Infertility Outcomes in Patients with Polycystic Ovary Syndrome Undergoing Frozen Embryo Transfer:A Retrospective Cohort Study.

Purpose: It is well known that androgen excess impairs oocyte quality, endometrial receptivity and even embryo invasion to some extent. Free androgen index (FAI) is strongly recommended to evaluate active androgen. Previous studies have showed conflicting conclusions on the effect of hyperandrogenism on the pregnancy outcomes in patients with polycystic ovary syndrome (PCOS). This study aims to analyze the influence of hyperandrogenemia based on FAI on frozen embryo transfer (FET) outcomes in patients with PCOS. Patients and Methods: Patients diagnosed with PCOS who underwent their first FET between January 2017 and April 2022 were stratified into two cohorts using FAI, a highly recommended parameter: PCOS with hyperandrogenemia (n=73) and PCOS without hyperandrogenemia (n=255). Basic and infertility characteristics were analyzed using Student's t-test or chi-square (χ2) statistics. Logistic regression analysis was performed to verify whether FAI was helpful in predicting pregnancy outcomes in women with PCOS. Results: Body mass index (BMI), total gonadotropin (Gn), basal serum follicle-stimulating hormone (bFSH), basal serum testosterone (bT), sex hormone binding globulin (SHBG), and FAI were significantly different between the two groups. (P=0.005, P<0.001, P<0.001, P<0.001, and P<0.001, respectively). However, clinical pregnancies, abortions, and live births did not differ significantly. Further regression analyses showed that FAI was not related to clinical pregnancy, abortion, or live birth rates (adjusted odds ratio (OR)=0.978, 95% confidence interval (CI)=0.911-1.050, P=0.539; adjusted OR=1.033, 95% CI=0.914-1.168, P=0.604; and adjusted OR=0.976, 95% CI=0.911-1.047, P=0.499, respectively). Conclusion: FAI was not associated with pregnancy outcomes in patients with PCOS; that is, it did not reflect any negative effects of hyperandrogenemia on pregnancy outcomes in patients with PCOS and was not an informative clinical parameter. Therefore, more attention should be paid to the factors that influence the accuracy of FAI in reflecting androgen levels in vivo, and further discussion is needed.

FGF4 ameliorates the liver inflammation by reducing M1 macrophage polarization in experimental autoimmune hepatitis.

BACKGROUND: The global prevalence of autoimmune hepatitis (AIH) is increasing due in part to the lack of effective pharmacotherapies. Growing evidence suggests that fibroblast growth factor 4 (FGF4) is crucial for diverse aspects of liver pathophysiology. However, its role in AIH remains unknown. Therefore, we investigated whether FGF4 can regulate M1 macrophage and thereby help treat liver inflammation in AIH. METHODS: We obtained transcriptome-sequencing and clinical data for patients with AIH. Mice were injected with concanavalin A to induce experimental autoimmune hepatitis (EAH). The mechanism of action of FGF4 was examined using macrophage cell lines and bone marrow-derived macrophages. RESULTS: We observed higher expression of markers associated with M1 and M2 macrophages in patients with AIH than that in individuals without AIH. EAH mice showed greater M1-macrophage polarization than control mice. The expression of M1-macrophage markers correlated positively with FGF4 expression. The loss of hepatic Fgf4 aggravated hepatic inflammation by increasing the abundance of M1 macrophages. In contrast, the pharmacological administration of FGF4 mitigated hepatic inflammation by reducing M1-macrophage levels. The efficacy of FGF4 treatment was compromised following the in vivo clearance of macrophage populations. Mechanistically, FGF4 treatment activated the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-signal pathway in macrophages, which led to reduced M1 macrophages and hepatic inflammation. CONCLUSION: We identified FGF4 as a novel M1/M2 macrophage-phenotype regulator that acts through the PI3K-AKT-signaling pathway, suggesting that FGF4 may represent a novel target for treating inflammation in patients with AIH.

Functional determination of site-mutations in rdxA involved in metronidazole resistance of Helicobacter pylori.

Background: Metronidazole (MTZ) is among the first-line drugs against the human gastric pathogen Helicobacter pylori (H. pylori). MTZ is used as a prodrug that is activated by an oxygen-insensitive enzyme NADPH nitroreductase (RdxA). Loss-of-function mutations in rdxA make H. pylori MTZ resistant; however, experimental proof is lacking. Methods: We collected 139 gastric biopsy samples from patients suspected of H. pylori infection in Shanghai, and amplified Hp-specific rdxA gene from 134 samples. All these rdxA genes were sequenced and phylogenetically compared. The effect of mutations on RdxA function was measured by expressing them in Escherichia coli DH5α by using the MTZ sensitivity test. Results: In total, 134 gastric biopsy samples were identified as H. pylori positive. Of the 134 samples, 74 and 6 had point mutations at the various sites or promoter region of rdxA, generating truncated and extended fused proteins, respectively. The remaining 54 were full-length with single nucleotide variation (SNV) compared with the wild-type RdxA from H. pylori, with 49 clustering with hpEastAsia, 3 with hpEurope, and 2 with hpNEAfrica. All 134 rdxA were expressed in E. coli DH5α; 22 and 112 resultant strains showed MTZ-sensitive and MTZ-resistant phenotypes, respectively. Comparative analysis of single nucleotide polymorphisms (SNPs) in the functional and inactivated RdxA revealed 14 novel mutations in RdxA, 5 of which conferred MTZ resistance: S18F, D59S, L62I, S79N, and A187V. Conclusion: The occurrence of MTZ resistance induced by site-mutation of RdxA in patients with H. pylori infection was 83.6% (112/134) in the Shanghai region. The major form of loss-of-function mutation was truncation of RdxA translation at a rate of 58/112 (51.8%). Molecular detection reliably determined the resistance of H. pylori to MTZ. Thus, the functional mutants involved in MTZ resistance facilitate clinical diagnosis and medication based on sequence analysis.

[The effect of erbium laser pretreatment on bond strength between dentin and enamel and microleakage at the edge of CAD/CAM glass ionomer cement restorations for repairing tooth defects].

PURPOSE: To investigate the effects of erbium laser pretreatment on the bond strength of dentin and enamel,as well as microleakage at the edge of tooth defects repaired with computer-aided design (CAD) and computer-assisted manufacturing (CAM) glass-ceramic restorations for repairing dental defects. METHODS: A total of 62 fresh, nondecayed, nondiscoloration and noncracked wisdom teeth were collected from the Oral Surgery Clinic between January 2020 and January 2023. According to different pretreatment methods, they were randomly divided into two groups, erbium laser group and phosphoric acid group, with 31 teeth in each group. Each group was further divided into two subsets for bond strength testing (16 teeth) and microleakage testing (15 teeth).The shear bond strength between enamel and dentin of both groups was compared, as well as the degree and distribution of microleakage.Statistical analysis was performed with SPSS 17.0 software package. RESULTS: The shear bond strength between enamel and dentin of the erbium laser group was significantly higher than that of the phosphoric acid group (P＜0.05); the degree and distribution of microleakage at the lateral walls and gumline of the erbium laser group were significantly lower than those of the phosphoric acid group (P＜0.05). The scores of microleakage at the lateral walls of the erbium laser group mainly concentrated in grade 1 and 2, whereas those of the phosphoric acid group mainly concentrated in grade 2. There was significant difference in the distribution of lateral wall microleakage scores between the two groups (P＜0.05). The scores of microleakage at the gumline of the erbium laser group mainly concentrated in grade 1 and 2, whereas those of the phosphoric acid group mainly concentrated in grade 2 and 3. There was significant difference in the distribution of gumline microleakage scores between the two groups (P＜0.05). CONCLUSIONS: Erbium laser pretreatment can improve bonding strength between glass ionomer cement and dentin and enamel, reduce microleakage at the edge of CAD/CAM glass ionomer cement restorations, and enhance marginal fit.

In-Sensor Organic Electrochemical Transistor for the Multimode Neuromorphic Olfactory System.

The olfactory system is one of the six basic sensory nervous systems. Developing artificial olfactory systems is challenging due to the complexity of chemical information decoding and memory. Conventional chemical sensors can convert chemical signals into electric signals to decode gas information but they lack memory functions. Additional storage and processing units would significantly increase the complexity and power consumption of the devices, especially for portable and wearable devices. Here, an olfactory-inspired in-sensor organic electrochemical transistor (OI-OECT) is proposed, with the integrated functions of chemical information decoding, tunable memory level, and selectivity of vapor sensing. The ion-gel electrolyte endows the OI-OECT with the function of tunable memory levels and a low operating voltage. Typical synaptic behaviors, including inhibitory postsynaptic current and paired-pulse facilitations, are successfully achieved. Importantly, the gas memory level can be effectively modulated by the gate voltages (0 and -1 V), which realized the transformation of volatile and nonvolatile memory. Furthermore, benefiting from the recognition of multiple gases and ability to detect cumulative damage caused by gases, the OI-OECT is demonstrated for early warning system targeting leakage detection of two gases (NH3 and H2S). This work achieves the integrated functions of chemical gas information decode, tunable gas memory level, and selectivity of gas in a single device, which provides a promising pathway for the development of future artificial olfactory systems.

Characterization and identification of the wide-polarity multicomponents from Prunella vulgaris by offline two-dimensional liquid chromatography and hydrophilic interaction chromatography coupled to ion mobility-quadrupole time-of-flight mass spectrometry.

Metabolites identification is crucial to develop functional foods or perform quality control. Prunella vulgaris (Xia-Ku-Cao) is a medicinal and edible plant used as the herbal medicine or main additive in functional beverage. However, current analytical strategies can only on-line characterize tens of compounds, restricted by insufficient chromatographic resolution and low coverage of the mass spectrometric scan methods. This work was designed to characterize the wide-polarity components from the ear of P. vulgaris. The total extract was fractionated by semi-preparative high-performance liquid chromatography into the retained medium-polarity fraction and unretained polar fraction, which were further analyzed by offline two-dimensional liquid chromatography (2D-LC) and hydrophilic interaction chromatography, respectively. Data-independent high-definition MSE of the Vion™ ion mobility time-of-flight mass spectrometer was utilized enabling the high-coverage acquisition of collision-induced dissociation-MS2 data. The offline 2D-LC, configuring the XBridge Amide and HSS T3 columns, gave high orthogonality (0.81) and effective peak capacity (1555). Automatic peak annotation facilitated by the UNIFI™ bioinformatics platform and comparison with 62 reference compounds achieved the efficient and more reliable structural elucidation. We could characterize 255 compounds from P. vulgaris, with numerous phenylpropanoid phenolic acids and triterpenoid O-glycosides newly reported. Especially, collision cross section (CCS) prediction and targeted isolation of three compounds assisted in the identification of 39 groups of isomers. Additionally, 17 hydrophilic compounds, involving oligosaccharides and organic acids, were characterized from the unretained polar fraction. Conclusively, the in-depth metabolites identification of P. vulgaris was accomplished, and the results can benefit the development and better quality control of this valuable plant.

Correction of High Astigmatism by Autologous Astigmatic Lenticule Reshaping and Rotation.

PURPOSE: To explore the use of autologous astigmatic lenticule reshaping and rotation surgery to correct high astigmatism in conjunction with excimer laser technology to correct residual refractive error. METHODS: Six patients with high astigmatism (8 eyes, all with astigmatism from -5.50 to -11.00 diopters [D]) seeking refractive error correction were enrolled. The following methods were used to correct refractive errors that could not be corrected by a single conventional surgery: (1) cutting of a customized lens using FLEx technology, (2) lifting of the corneal flap and reshaping the autologous astigmatic lenticule in situ using an excimer laser, and (3) rotation of the autologous astigmatic lenticule by 90°. Uncorrected distance visual acuity, subjective refraction, corneal topography, and anterior segment optical coherence tomography were performed preoperatively and postoperatively. RESULTS: The efficacy and safety indices at 6 months postoperatively were 0.93 ± 0.18 and 1.06 ± 0.11, respectively, the spherical equivalent remained stable and close to emmetropia (-0.13 ± 0.70 D) from 1 to 6 months postoperatively, postoperative astigmatism was generally mildly undercorrected (-1.22 ± 0.43 D), and the difference in corneal curvatures at 2 mm from the apex of the cornea was significantly reduced compared to preoperatively (P < .05); however, the corresponding values at 1 and 3 mm showed no difference. CONCLUSIONS: Correction of high astigmatism with autologous astigmatic lenticule reshaping and rotation surgery is tissue-sparing, predictable, and significantly improves postoperative visual acuity and quality. This method is feasible and safe, with predictability requiring further study. This novel surgical approach has potential for patients with high astigmatism that cannot be corrected by conventional refractive surgery. [J Refract Surg. 2024;40(8):e554-e561.].

oHSV2-mGM repolarizes TAMs and cooperates with αPD1 to reprogram the immune microenvironment of residual cancer after radiofrequency ablation.

BACKGROUND: Due to the size and location of the tumor, incomplete radiofrequency ablation (iRFA) of the target tumor inhibits tumor immunity. In this study, a murine herpes simplex virus (oHSV2-mGM) armed with granulocyte-macrophage colony-stimulating factor (GM-CSF) was constructed to explore its effect on innate and adaptive immunity during iRFA, and the inhibitory effect of programmed cell death-1 (PD1) on tumor. METHODS: We verified the polarization and activation of RAW264.7 cells mediated by oHSV2-mGM in vitro. Subsequently, we evaluated the efficacy of oHSV2-mGM alone and in combination with αPD1 in the treatment of residual tumors after iRFA in two mouse models. RNA-seq was used to characterize the changes of tumor microenvironment. RESULTS: oHSV2-mGM lysate effectively stimulated RAW264.7 cells to polarize into M1 cells and activated M1 phenotypic function. In the macrophage clearance experiment, oHSV2-mGM activated the immune response of tumor in mice. The results in vivo showed that oHSV2-mGM showed better anti-tumor effect in several mouse tumor models. Finally, oHSV2-mGM combined with PD1 antibody can further enhance the anti-tumor effect of oHSV2-mGM and improve the complete remission rate of tumor in mice. CONCLUSION: The application of oHSV2-mGM leads to the profound remodeling of the immune microenvironment of residual tumors. oHSV2-mGM also works in synergy with PD1 antibody to achieve complete remission of tumors that do not respond well to monotherapy at immune checkpoints. Our results support the feasibility of recombinant oncolytic virus in the treatment of residual tumors after iRFA, and propose a new strategy for oncolytic virus treatment of tumors.

Increased adrenal steroidogenesis and suppressed corticosteroid responsiveness in critical COVID-19.

BACKGROUND: The effect of coronavirus disease 2019 (COVID-19) on adrenal endocrine metabolism in critically ill patients remains unclear. This study aimed to investigate the alterations in adrenal steroidogenic activity, elucidate underlying mechanisms, provide in situ histopathological evidence, and examine the clinical implications. METHODS: The comparative analyses of the adrenal cortices from 24 patients with fatal COVID-19 and 20 matched controls was performed, excluding patients previously treated with glucocorticoids. Several SARS-CoV-2 and its receptors were identified and pathological alterations were examined. Furthermore, histological examinations, immunohistochemical staining and ultrastructural analyses were performed to assess corticosteroid biosynthesis. The zona glomerulosa (ZG) and zona fasciculata (ZF) were then dissected for proteomic analyses. The biological processes that affected steroidogenesis were analyzed by integrating histological, proteomic, and clinical data. Finally, the immunoreactivity of mineralocorticoids and glucocorticoid receptors in essential tissues were quantitatively measured to evaluate corticosteroid responsiveness. FINDINGS: The demographic characteristics of COVID-19 patients were comparable with those of controls, excluding those that affected adrenal function. SARS-CoV-2-like particles were identified in the adrenocortical cells of three patients; however, these particles did not affect cellular morphology or steroid synthesis compared with those in SARS-CoV-2-negative specimens. Although the adrenals exhibited focal necrosis, vacuolization, microthrombi, and inflammation, widespread degeneration was not evident. Notably, corticosteroid biosynthesis was significantly enhanced in both the ZG and ZF of COVID-19 patients. The increase in the inflammatory response and cellular differentiation in the adrenal cortices of patients with critical COVID-19 was positively correlated with heightened steroidogenic activity. Additionally, the appearance of more dual-ZG/ZF identity cells in COVID-19 adrenals was in accordance with the increased steroidogenic function. However, activated mineralocorticoid and glucocorticoid receptors in vital tissues were markedly reduced in patients with critical COVID-19. INTERPRETATION: Critical COVID-19 was characterized by potentiated adrenal steroidogenesis, associated with exacerbation of inflammation, differentiation and the presence of dual-ZG/ZF identity cells. These alterations implied the reduced effectiveness of conventional corticosteroid therapy and underscored the need for evaluation of adrenal axis and the corticosteroid sensitivity.

scDrug+: predicting drug-responses using single-cell transcriptomics and molecular structure.

Predicting drug responses based on individual transcriptomic profiles holds promise for refining prognosis and advancing precision medicine. Although many studies have endeavored to predict the responses of known drugs to novel transcriptomic profiles, research into predicting responses for newly discovered drugs remains sparse. In this study, we introduce scDrug+, a comprehensive pipeline that seamlessly integrates single-cell analysis with drug-response prediction. Importantly, scDrug+ is equipped to predict the response of new drugs by analyzing their molecular structures. The open-source tool is available as a Docker container, ensuring ease of deployment and reproducibility. It can be accessed at https://github.com/ailabstw/scDrugplus.

Twin-Field Quantum Key Distribution with Local Frequency Reference.

Twin-field quantum key distribution (TFQKD) overcomes the linear rate-loss limit, which promises a boost of secure key rate over long distance. However, the complexity of eliminating the frequency differences between the independent laser sources hinders its practical application. We analyzed and determined the frequency stability requirements for implementing TFQKD using frequency-stabilized lasers. Based on this analysis, we proposed and demonstrated a simple and practical approach that utilizes the saturated absorption spectroscopy of acetylene as an absolute reference, eliminating the need for fast frequency locking to achieve TFQKD. Adopting the 4-intensity sending-or-not-sending TFQKD protocol, we experimentally demonstrated the TFQKD over 502, 301, and 201 km ultralow-loss optical fiber, respectively. We expect this high-performance scheme will find widespread usage in future intercity and free-space quantum communication networks.

Sensitive detection of H2S based on Ce doped ZnCo2O4 hollow microspheres at low working temperature.

In order to develop a highly efficient H2S gas sensor at low working temperature, in this work, a kind of novel Ce-doped ZnCo2O4 hollow microspheres (Ce/ZnCo2O4 HMSs) were successfully synthesized using a template-free one-pot method, showing a sensitive response toward H2S. The microstructure and morphology of the material were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The gas-sensing performance of the composite was investigated, showing that the ZnCo2O4 doped with 6 mol% Ce had the highest response to 20 ppm H2S at a low operating temperature of 160 °C with a response value of 67.42, which was about 2 times higher than that of original ZnCo2O4. The prepared Ce/ZnCo2O4 HMS sensor in response to H2S exhibited a linear range of 0.1-200 ppm with a low detection limit of 0.1 ppm under the conditions of ambient humidity of 45% and ambient temperature of 20 °C. Meanwhile, it also possessed good selectivity, repeatability and reproducibility. The response value of the sensor decreased by 5.32% after 7 months of continuous monitoring of H2S in an atmospheric environment of a pig farm, indicating that the sensor had a long-term stability and continuous service life with important application prospects.

Revisiting the Electrochemical Impedance Spectroscopy of Porous Electrodes in Li-ion Batteries by Employing Reference Electrode.

Electrochemical impedance spectroscopy (EIS), characterized by its non-destructive and in-situ nature, plays a crucial role in comprehending the thermodynamic and kinetic processes occurring with Li-ion batteries. However, there is a lack of consistent and coherent physical interpretations for the EIS of porous electrodes. Therefore, it is imperative to conduct thorough investigations into the underlying physical mechanisms of EIS. Herein, by employing reference electrode in batteries, we revisit the associated physical interpretation of EIS at different frequency. Combining different battery configurations, temperature-dependent experiments, and elaborated distribution of relaxation time analysis, we find that the ion transport in porous electrode channels and pseudo-capacitance behavior dominate the high-frequency and mid-frequency impedance arcs, respectively. This work offers a perspective for the physical interpretation of EIS and also sheds light on the understanding of EIS characteristics in other advanced energy storage systems.

Highly Efficient Electrosynthesis of Urea from CO2 and Nitrate by a Metal-Organic Framework with Dual Active Sites.

Electrosynthesis of urea from CO2 and NO3- is a sustainable alternative to energy-intensive industrial processes. The challenge hindering the progress is the development of advanced electrocatalysts that yield urea with both high Faradaic efficiency (FE) and current density. In this work, we designed a new two-dimensional MOF, namely PcNi-Fe-O, constructed by nickel-phthalocyanine (NiPc) ligands and square-planar FeO4 nodes. PcNi-Fe-O exhibits remarkable performance to yield urea at a high current density of 10.1 mA cm-2 with a high FE(urea) of 54.1% in a neutral aqueous solution, surpassing those of most reported electrocatalysts. No obvious performance degradation was observed over 20 hours of continuous operation at the current density of 10.1 mA cm-2. By expanding the electrode area to 25 cm2 and operating for 8 hours, we obtained 0.164 g of high-purity urea, underscoring its potential for industrial applications. Mechanism study unveiled the enhanced performance might be ascribed to the synergistic interaction between NiPc and FeO4 sites. Specifically, NH3 produced at the FeO4 site can efficiently migrate and couple with the *NHCOOH intermediate adsorbed on the urea-producing site (NiPc). This synergistic effect results in a lower energy barrier for C-N bond formation than those of the reported catalysts with single active sites.