Dietary effects of vitamin C on antioxidant capacity, intestinal microbiota and the resistance of pathogenic bacteria in cultured Silver pomfret (Pampus argenteus).

As most teleosts are unable to synthesize vitamin C, supplemental diets containing vitamin C diets play a crucial role in fish health. The aim of this study was to investigate the effect of dietary vitamin C on the intestinal enzyme activity and intestinal microbiota of silver pomfre (Pampus argenteus). Four experimental diets were supplemented with basic diets containing 300 mg of vitamin C/kg (group tjl3), 600 mg of vitamin C/kg (group tjl6), and 1200 mg of vitamin C/kg (group tjl12), as well as vitamin C-free supplemental basic diet (group tjl0), respectively. The four diets were fed to juvenile P. argenteus (average initial weight: 4.68 ± 0.93 g) for 6 weeks. The results showed that the activity of SOD (superoxide dismutase) and CAT (catalase) increased significantly while that of MDA (malondialdehyde) decreased significantly in group tjl3 compared to vitamin group tjl0. At the genus level, groups tjl0, tjl6, and tjl12 contained the same dominant microbial community, Stenotrophomonas, Photobacterium, and Vibrio, whereas group tjl3 was dominated by Stenotrophomonas, Delftia, and Bacteroides. Among the fish fed with a basic diet containing 300 mg of vitamin C/kg, the intestines exhibited a notable abundance of probiotic bacteria, including lactic acid bacteria (Lactobacillus) and Bacillus. The abundance of Aeromonas in groups tjl3 and tjl6 was lower than that of the vitamin C-free supplemental basic diet group, whereas Aeromonas was not detected in group tjl12. In addition, a causative agent of the disease outbreak in cultured P. argenteus, Photobacterium damselae subsp. Damselae (PDD) was the dominant microbiota community in groups tjl0, tjl6 and tjl12, whereas the abundance of PDD in group tjl3 was the lowest among the diets. Taken together, the diets supplied with vitamin C could influence the composition microbial community of P. argenteus. The low level of vitamin C (300 mg of vitamin C/kg per basic diet) supplementation could not only improve the antioxidant capacity but also resist the invasion of pathogenic bacteria.

Crystal structural effects on up/down-conversion luminescence properties of GdInO3:Tm,Yb perovskite phosphors for effective dual-mode anti-counterfeit applications.

Developing advanced luminescent materials that are recognizable under specified conditions provides better opportunity for reliable optical anti-counterfeiting techniques. In this work, to the best of our knowledge, novel GdInO3:Tm,Yb perovskite phosphors with ultrafine sizes and rounded morphologies were successfully synthesized by a facile chemical precipitation route. Two-type perovskites with orthorhombic and hexagonal structures could be obtained by calcining the precursor at 850 and 1100 °C, respectively. Under 980 nm excitation, the two phosphors exhibited cyan-bluish emission at ∼460-565 nm, red emission at 645-680 nm, and near-infrared emission at 770-825 nm arising from 1G4 + 1D2→3H5,6, 3F2,3→3H6, and 3H4→3H6 transitions of Tm3+, respectively, where the hexagonal perovskite phosphor had relatively strong and sharp red emission as well as red-shifted cyan-bluish emission via successive cross relaxations. The Yb3+ sensitizer enhanced the upconversion luminescence via effective Yb3+→Tm3+ energy transfer and the optimal Yb3+ concentrations were 10 at.% for orthorhombic perovskite and 5 at.% for hexagonal one. The upconversion mechanism mainly ascribed to two-photon processes while three-photon was also present. Upon excitation at 254 nm, their down-conversion spectra exhibited broad multibands in the wavelength range of 400-500 nm deriving from combined effects of the defect-induced emission of GdInO3 and the 1D2→3F4 + 4G4→3H6 emissions of Tm3+. The energy transfer from GdInO3 defect level to Tm3+ excitation state was observed for the first time. The unclonable security codes prepared by screen printing from those dual-mode emitting perovskite phosphors were almost invisible under natural light, which had promising potential for anti-counterfeiting application.

Linguistic dissection of nursing handoffs: Implications for patient safety in varied-acuity hospital settings.

AIM: This study examines the intricate language and communication patterns of nurse-to-nurse handoffs across three units with varying patient acuity levels and nurse-patient ratios, seeking to identify linguistic factors that may affect the quality of information transfer and patient outcomes. DESIGN: A mixed-methods cross-sectional design. METHODS: This study used the Nurse-to-Nurse Transition of Care Communication Model to explore the content and meaning of language in nursing handoffs within a large academic medical centre. Data were collected on three units through digital audio recordings of 20 handoffs between June and September 2022, which were transcribed and analysed using the Linguistic Inquiry Word Count programme. Trustworthiness was established by adhering to COREQ and STROBE guidelines for qualitative and quantitative research, respectively. RESULTS: Analysis revealed a preference for casual, narrative language across all units, with ICU nurses demonstrating a higher confidence and leadership in communication. Cognitive processes such as insight and causation were found to be underrepresented, indicating a potential area for miscommunication. Communication motives driven by affiliation were more pronounced in ICU settings, suggesting a strong collaborative nature. No significant differences were observed among the units post multiple testing adjustments. Speech dysfluencies were most pronounced in ICU handoffs, reflecting possible stress and cognitive overload. CONCLUSION: The study highlights the need for improved communication strategies such as interventions to enhance language clarity and incorporating technological tools into handoff processes to mitigate potential miscommunications and errors. The findings advance nursing science by highlighting the critical role of nuanced language in varied-acuity hospital settings and the necessity for structured nurse education in handoff communication and standardized handoff procedures. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: This study underscores the critical role of language in nurse-to-nurse handoffs. It calls for enhanced communication strategies, technology integration and training to reduce medical errors, improving patient outcomes in high-acuity hospital settings. PATIENT OR PUBLIC CONTRIBUTION: Nurses only.

Hierarchical Porous N-Doped Carbon Particles Derived from ZIF-8 as Highly Efficient H2S Selective Oxidation Catalysts.

In the selective oxidation of H2S, the catalytic activity over N-doped carbon-based catalysts is significantly influenced by the accessibility of active sites and the mass transfer rates of reactant molecules (e.g., H2S and O2) as well as generated sulfur monomers. Therefore, it is crucial for enhancing the initial performance via the controlled synthesis of carbon-based catalysts with highly exposed active sites and unique porous structures. Herein, we reported on an efficient strategy to synthesize nanosized N-doped carbon particles with hierarchical porous structures by directly pyrolyzing an oversaturated NaCl-encapsulated ZIF-8 precursor mixture. The introduction of NaCl not only serves as a pollution-free template to promote the formation of graphitic carbon layers but also acts as an intercalating agent to guide the derivation of hierarchical porous structures, as well as enhances the amount of active nitrogen species in the catalysts. As a result, the as-prepared H-NC800 catalyst shows excellent H2S selective oxidation performance (sulfur formation rate is 794 gsulfur·kgcat-1·h-1), good stability (>80 h), and antiwater vapor properties. The characterization results and DFT calculations indicate the crucial role of pyridinic N in the adsorbing and activating reactant molecules (H2S, O2). Furthermore, nanoscale N-doped carbon particles accelerated the rapid transport of generated sulfur monomers under a hierarchical porous structure. This investigation introduces a distinctive strategy for synthesizing ZIF-8-derived N-doped carbon nanosized with a hierarchical porous structure, while its efficient and stable H2S selective oxidation performance highlights significant potential for practical implementation in the industrial desulfurization process.

Research strategies of small molecules as chemotherapeutics to overcome multiple myeloma resistance.

Multiple myeloma (MM), a cancer of plasma cells, is the second most common hematological malignancy which is characterized by aberrant plasma cells infiltration in the bone marrow and complex heterogeneous cytogenetic abnormalities. Over the past two decades, novel treatment strategies such as proteasome inhibitors, immunomodulators, and monoclonal antibodies have significantly improved the relative survival rate of MM patients. However, the development of drug resistance results in the majority of MM patients suffering from relapse, limited treatment options and uncontrolled disease progression after relapse. There are urgent needs to develop and explore novel MM treatment strategies to overcome drug resistance and improve efficacy. Here, we review the recent small molecule therapeutic strategies for MM, and introduce potential new targets and corresponding modulators in detail. In addition, this paper also summarizes the progress of multi-target inhibitor therapy and protein degradation technology in the treatment of MM.

Reconstruction of a three-dimensional temperature field in flames based on ES-ResNet18.

Currently, the method of establishing the correspondence between the flame light field image and the temperature field by deep learning is widely used. Based on convolutional neural networks (CNNs), the reconstruction accuracy has been improved by increasing the depth of the network. However, as the depth of the network increases, it will lead to gradient explosion and network degradation. To further improve the reconstruction accuracy of the flame temperature field, this paper proposes an ES-ResNet18 model, in which SoftPool is used instead of MaxPool to preserve feature information more completely and efficient channel attention (ECA) is introduced in the residual block to reassign more weights to feature maps of critical channels. The reconstruction results of our method were compared with the CNN model and the original ResNet18 network. The results show that the average relative error and the maximum relative error of the temperature field reconstructed by the ES-ResNet18 model are 0.0203% and 0.1805%, respectively, which are reduced by one order of magnitude compared to the CNN model. Compared to the original ResNet18 network, they have decreased by 17.1% and 43.1%, respectively. Adding Gaussian noise to the flame light field images, when the standard deviation exceeds 0.03, the increase in reconstruction error of the ES-ResNet18 model is lower than that of ResNet18, demonstrating stronger anti-noise performance.

HIV-1 capsid stability and reverse transcription are finely balanced to minimize sensing of reverse transcription products via the cGAS-STING pathway.

A critical determinant for early post-entry events, the HIV-1 capsid (CA) protein forms the conical core when it rearranges around the dimeric RNA genome and associated viral proteins. Although mutations in CA have been reported to alter innate immune sensing of HIV-1, a direct link between core stability and sensing of HIV-1 nucleic acids has not been established. Herein, we assessed how manipulating the stability of the CA lattice through chemical and genetic approaches affects innate immune recognition of HIV-1. We found that destabilization of the CA lattice resulted in potent sensing of reverse transcription products when destabilization per se does not completely block reverse transcription. Surprisingly, due to the combined effects of enhanced reverse transcription and defects in nuclear entry, two separate CA mutants that form hyperstable cores induced innate immune sensing more potently than destabilizing CA mutations. At low concentrations that allowed the accumulation of reverse transcription products, CA-targeting compounds GS-CA1 and lenacapavir measurably impacted CA lattice stability in cells and modestly enhanced innate immune sensing of HIV. Interestingly, innate immune activation observed with viruses containing unstable cores was abolished by low doses of lenacapavir. Innate immune activation observed with both hyperstable and unstable CA mutants was dependent on the cGAS-STING DNA-sensing pathway and reverse transcription. Overall, our findings demonstrate that CA lattice stability and reverse transcription are finely balanced to support reverse transcription and minimize cGAS-STING-mediated sensing of the resulting viral DNA. IMPORTANCE: In HIV-1 particles, the dimeric RNA genome and associated viral proteins and enzymes are encased in a proteinaceous lattice composed of the viral capsid protein. Herein, we assessed how altering the stability of this capsid lattice through orthogonal genetic and chemical approaches impacts the induction of innate immune responses. Specifically, we found that decreasing capsid lattice stability results in more potent sensing of viral reverse transcription products, but not the genomic RNA, in a cGAS-STING-dependent manner. The recently developed capsid inhibitors lenacapavir and GS-CA1 enhanced the innate immune sensing of HIV-1. Unexpectedly, due to increased levels of reverse transcription and cytosolic accumulation of the resulting viral cDNA, capsid mutants with hyperstable cores also resulted in the potent induction of type I interferon-mediated innate immunity. Our findings suggest that HIV-1 capsid lattice stability and reverse transcription are finely balanced to minimize exposure of reverse transcription products in the cytosol of host cells.

Discovery of RORγ Allosteric Fluorescent Probes and Their Application: Fluorescence Polarization, Screening, and Bioimaging.

Retinoic acid receptor-related orphan receptor γ (RORγ) acts as a crucial transcription factor in Th17 cells and is involved in diverse autoimmune disorders. RORγ allosteric inhibitors have gained significant research focus as a novel strategy to inhibit RORγ transcriptional activity. Leveraging the high affinity and selectivity of RORγ allosteric inhibitor MRL-871 (1), this study presents the design, synthesis, and characterization of 11 allosteric fluorescent probes. Utilizing the preferred probe 12h, we established an efficient and cost-effective fluorescence polarization-based affinity assay for screening RORγ allosteric binders. By employing virtual screening in conjunction with this assay, 10 novel RORγ allosteric inhibitors were identified. The initial SAR studies focusing on the hit compound G381-0087 are also presented. The encouraging outcomes indicate that probe 12h possesses the potential to function as a powerful tool in facilitating the exploration of RORγ allosteric inhibitors and furthering understanding of RORγ function.

The CARD8 inflammasome dictates HIV/SIV pathogenesis and disease progression.

While CD4+ T cell depletion is key to disease progression in people living with HIV and SIV-infected macaques, the mechanisms underlying this depletion remain incompletely understood, with most cell death involving uninfected cells. In contrast, SIV infection of "natural" hosts such as sooty mangabeys does not cause CD4+ depletion and AIDS despite high-level viremia. Here, we report that the CARD8 inflammasome is activated immediately after HIV entry by the viral protease encapsulated in incoming virions. Sensing of HIV protease activity by CARD8 leads to rapid pyroptosis of quiescent cells without productive infection, while T cell activation abolishes CARD8 function and increases permissiveness to infection. In humanized mice reconstituted with CARD8-deficient cells, CD4+ depletion is delayed despite high viremia. Finally, we discovered loss-of-function mutations in CARD8 from "natural hosts," which may explain the peculiarly non-pathogenic nature of these infections. Our study suggests that CARD8 drives CD4+ T cell depletion during pathogenic HIV/SIV infections.

Caffeine in Hepatocellular Carcinoma: Cellular Assays, Animal Experiments, and Epidemiological Investigation.

The use of caffeine in treating various liver diseases has made substantial progress in the past decade owing to advances in science, technology, and medicine. However, whether caffeine has a preventive effect on hepatocellular carcinoma (HCC) and its mechanism are still worth further investigation. In this review, we summarize and analyze the efficacy and safety of caffeine in the prevention of HCC. We conducted a review of articles published in PubMed and Web of Science in the past 2 decades until December 6, 2023, which were searched for using the terms "Caffeine" and "Hepatocellular Carcinoma." Studies have found that coffee intake is negatively correlated with HCC risk, especially caffeinated coffee. Recent studies have found that caffeine has beneficial effects on liver health, decreasing levels of enzymes responsible for liver damaging and slowing the progression of hepatic fibrosis and cirrhosis. Caffeine also acts against liver fibrosis through adenosine receptors (ARs), which promote tissue remodeling by inducing fibrin and collagen production. Additionally, new studies have found that moderate consumption of caffeinated beverages can decrease various the levels of various collagens in patients with chronic hepatitis C. Furthermore, polyphenolic compounds in coffee can improve fat homeostasis, reduce oxidative stress, and prevent liver steatosis and fibrosis. Moreover, many in vitro studies have shown that caffeine can protect liver cells and inhibit the activation and proliferation of hepatic stellate cells. Taken together, we describe the benefits of caffeine for liver health and highlight its potential values as a drug to prevent various hepatic diseases. As a protective agent of liver inflammation, non-selective AR inhibitor caffeine can inhibit the growth of HCC cells by inhibiting adenosine and AR binding to initiate immune response, providing a basis for the future development of caffeine as an adjuvant drug against HCC.

Unraveling the Promise of RET Inhibitors in Precision Cancer Therapy by Targeting RET Mutations.

Over the past decades, the role of rearranged during transfection (RET) alterations in tumorigenesis has been firmly established. RET kinase inhibition is an essential therapeutic target in patients with RET-altered cancers. In clinical practice, initial efficacy can be achieved in patients through the utilization of multikinase inhibitors (MKIs) with RET inhibitory activity. However, the effectiveness of these MKIs is impeded by the adverse events associated with off-target effects. Recently, many RET-selective inhibitors, characterized by heightened specificity and potency, have been developed, representing a substantial breakthrough in the field of RET precision oncology. This Perspective focuses on the contemporary understanding of RET mutations, recent advancements in next-generation RET inhibitors, and the challenges associated with resistance to RET inhibitors. It provides valuable insights for the development of next-generation MKIs and selective RET inhibitors.

Design and synthesis 1H-Pyrrolo[2,3-b]pyridine derivatives as FLT3 inhibitors for the treatment of Acute myeloid Leukemia.

Acute myeloid leukemia (AML) is the most common type of blood cancer and has been strongly correlated with the overexpression of Fms-like tyrosine kinase 3 (FLT3), a member of the class III receptor tyrosine kinase family. With the emergence of FLT3 internal tandem duplication alteration (ITD) and tyrosine kinase domain (TKD) mutations, the development of FLT3 small molecule inhibitors has become an effective medicinal chemistry strategy for AML. Herein, we have designed and synthesized two series of 1H-pyrrolo[2,3-b]pyridine derivatives CM1-CM24, as FLT3 inhibitors based on F14, which we previously reported, that can target the hydrophobic FLT3 back pocket. Among these derivates, CM5 showed significant inhibition of FLT3 and FLT3-ITD, with inhibitory percentages of 57.72 % and 53.77 % respectively at the concentration of 1 µΜ. Furthermore, CM5 demonstrated potent inhibition against FLT3-dependent human AML cell lines MOLM-13 and MV4-11 (both harboring FLT3-ITD mutant), with IC50 values of 0.75 µM and 0.64 µM respectively. In our cellular mechanistic studies, CM5 also effectively induces apoptosis by arresting cell cycle progression in the G0/G1 phase. In addition, the amide and urea linker function were discussed in detail based on computational simulations studies. CM5 will serve as a novel lead compound for further structural modification and development of FLT3 inhibitors specifically targeting AML with FLT3-ITD mutations.

Neighborhood-level disadvantages increase risk for invasive pneumococcal disease.

BACKGROUND: Streptococcus pneumoniae (Spn) infection remains common worldwide despite recent vaccine efforts. Invasive pneumococcal disease (IPD) is the most severe form of Spn infection. Known individual risk factors for IPD include male gender and African American race. However, area-level socioeconomic factors have not been assessed. We examined the association of neighborhood-level disadvantages and risk of IPD in a tertiary medical center located in a socioeconomic diverse urban area in the Southeastern United States. METHODS: Patients hospitalized with culture-confirmed Streptococcus pneumoniae (Spn) infection from 01/01/2010 - 12/31/2019 were identified from electronic health record (EHR). The cohort's demographic and clinical information were obtained from EHR. Patients' residential address was geocoded and matched to 2015 area deprivation index (ADI). The association of ADI and IPD was evaluated using logistic regression after controlling for the demographic information (age, sex, race) and clinical factors (BMI, smoking status, alcoholism, immunosuppressive status, vaccination status, comorbidities). RESULTS: A total of 268 patients were hospitalized with culture-positive Streptococcus pneumoniae infection and 92 (34.3%) of them had IPD. The analysis showed that higher neighborhood deprivation (ADI in 79-100) was associated with increased risk of developing IPD in younger patients with age less than 65 (p = 0.007) after controlling for the individual demographic information and clinical factors. CONCLUSIONS: ADI is a risk factor for IPD in younger adults. Community-level socioeconomic risk factors should be considered when developing prevention strategies such as increasing vaccine uptake in high risk population to reduce the disease burden of IPD.

Characterizing the spectrum of bladder health and lower urinary tract symptoms among men: Results from the CARDIA study.

OBJECTIVES: To operationalize a new definition for bladder health, we examined the distribution and impact of lower urinary tract symptoms (LUTS), along with risk factors, among men in the Coronary Artery Risk Development in Young Adults (CARDIA) study. METHODS: LUTS were defined by American Urologic Association Symptom Index (AUASI) scores and impact on quality of life (QoL). Separate questions assessed urinary incontinence (UI) and postvoid dribbling. We performed cluster analyses using AUASI scores, with and without urine incontinence and postvoid dribbling, and impact collected in 2010-11. We performed analyses to evaluate sociodemographic and cardiovascular risk factors between clusters. RESULTS: Among CARDIA men (mean age: 50.0, SD = 3.6; range: 42-56 years) with complete LUTS data (n = 929), we identified and compared four clusters: men who reported no or very mild symptoms and no impact on well-being (bladder health, n = 696, 75%), men with moderate symptoms and moderate impact on well-being (moderate symptoms/impact, n = 84, 9%), men with high symptoms and high impact on well-being (severe symptoms/impact, n = 117, 13%), and a separate group that reported moderate symptoms and UI with a high impact on well-being (UI + moderate symptoms/severe impact, n = 32, 3%). Exploration of the groupings showed a large percentage of postvoid dribbling across groups (overall 69%). Sociodemographic and cardiovascular risk factors were not associated with symptom/impact groups. CONCLUSIONS: Bladder health clustered into four categories. A majority of middle-aged men in the community showed no or mild bladder symptoms without impact on QoL. Postvoid dribbling is pervasive but did not cluster with a specific LUTS or impact category.

Pharmacological approaches to promote cell death of latent HIV reservoirs.

PURPOSE OF REVIEW: HIV requires lifelong antiviral treatment due to the persistence of a reservoir of latently infected cells. Multiple strategies have been pursued to promote the death of infected cells. RECENT FINDINGS: Several groups have focused on multipronged approaches to induce apoptosis of infected cells. One approach is to combine latency reversal agents with proapoptotic compounds and cytotoxic T cells to first reactivate and then clear infected cells. Other strategies include using natural killer cells or chimeric antigen receptor cells to decrease the size of the reservoir.A novel strategy is to promote cell death by pyroptosis. This mechanism relies on the activation of the caspase recruitment domain-containing protein 8 (CARD8) inflammasome by the HIV protease and can be potentiated by nonnucleoside reverse transcriptase inhibitors. SUMMARY: The achievement of a clinically significant reduction in the size of the reservoir will likely require a combination strategy since none of the approaches pursued so far has been successful on its own in clinical trials. This discrepancy between promising in vitro findings and modest in vivo results highlights the hurdles of identifying a universally effective strategy given the wide heterogeneity of the HIV reservoirs in terms of tissue location, capability to undergo latency reversal and susceptibility to cell death.

AuNPs/CNC Nanocomposite with A "Dual Dispersion" Effect for LDI-TOF MS Analysis of Intact Proteins in NSCLC Serum Exosomes.

Detecting exosomal markers using laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS) is a novel approach for examining liquid biopsies of non-small cell lung cancer (NSCLC) samples. However, LDI-TOF MS is limited by low sensitivity and poor reproducibility when analyzing intact proteins directly. In this report, gold nanoparticles/cellulose nanocrystals (AuNPs/CNC) is introduced as the matrix for direct analysis of intact proteins in NSCLC serum exosomes. AuNPs/CNC with "dual dispersion" effects dispersed and stabilized AuNPs and improved ion inhibition effects caused by protein aggregation. These features increased the signal-to-noise ratio of [M+H]+ peaks by two orders of magnitude and lowered the detection limit of intact proteins to 0.01 mg mL-1. The coefficient of variation with or without AuNPs/CNC is measured as 10.2% and 32.5%, respectively. The excellent reproducibility yielded a linear relationship (y = 15.41x - 7.983, R2 = 0.989) over the protein concentration range of 0.01 to 20 mg mL-1. Finally, AuNPs/CNC-assisted LDI-TOF MS provides clinically relevant fingerprint information of exosomal proteins in NSCLC serum, and characteristic proteins S100 calcium-binding protein A10, Urokinase plasminogen activator surface receptor, Plasma protease C1 inhibitor, Tyrosine-protein kinase Fgr and Mannose-binding lectin associated serine protease 2 represented excellent predictive biomarkers of NSCLC risk.

A novel network-based adaptive fault-tolerant control of switched nonlinear systems subject to multiple faults under prescribed performance.

It is the first report about fault-tolerant-based prescribed performance control of switched nonlinear systems under multiple faults. The concerned faults include not only external faults but also actuator faults. In the process of backstepping control design, prescribed performance control is fully considered, and the combination of unknown nonlinear functions is estimated by multi-dimensional Taylor network. Finally, the developed adaptive fault-tolerant control strategy guarantees the boundedness of all controlled signals while prescribed tracking performance is satisfied. In an effort to further manifest the validity of the fault-tolerant controller, a numerical simulation and a practical simulation are introduced.

New insights into fibrotic signaling in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) mostly occurs in the background of liver fibrosis, and activated hepatic stellate cells (HSCs) exist in HCC tissues and adjacent tissues. HSC activation is involved throughout the development of HCC precancerous lesions, which has gradually attracted the attention of related researchers. In addition, HCC can promote the activation of HSCs, which in turn accelerates the occurrence and development of HCC by promoting tumor angiogenesis. In this review, we reviewed 264 studies from PubMed and ScienceDirect to summarize and analyze current significant fibrotic signaling in HCC. As a result, we found 10 fibrotic signaling pathways that are closely related to the activation, proliferation, invasion, migration, and promotion of apoptosis of HCC cells. In addition, we found that crosstalk between various fibrotic signaling pathways of HCC, hypoxia-induced energy metabolic reprogramming of HCC cells, matrix stiffness and stemness of HCC cells, and ferroptosis of HCC cells and HSCs are the latest research hotspots. Furthermore, related drugs that have been found to target these 10 fibrotic signaling pathways of HCC are listed. Our study provides a new reference for developing anti-HCC drugs.

Inhibiting Protein Aggregation Using Cellulose Nanocrystal in MALDI-TOF MS Analysis: Improving the Sensitivity and Repeatability of Intact Protein in Pueraria.

Protein aggregation can induce low sensitivity and poor repeatability of matrix-assisted laser desorption/ionization time-of-fight mass spectrometry (MALDI-TOF MS) analysis for intact protein. Herein, we introduced a strategy to decrease protein aggregation in the sample solution by using cellulose nanocrystal (CNC). The results indicated that protein granule size was effectively reduced by adding CNC to the sample solution. Through MALDI-TOF MS analysis, the signal-to-noise ratio of [M + H]+ peak increased 2-fold, and the detection of limit was <10 µg/mL for intact protein. The CNC also contributed to excellent point-to-point repeatability for MALDI-TOF MS analysis with the coefficient of variation (CV) of 10.0% with CNC vs 48.9% without CNC in Hb solution. Also, the repeatability of Pueraria protein ion signals was improved by using CNC, and the CV with and without CNC was 16.1% and 39.6%, respectively. Moreover, protein ion intensity exhibited great linear relationship (y = 53.04x - 3.474, R2 = 0.9936) with the concentrations (ranging from 0.1 to 10 mg/mL) when using CNC. Further investigation revealed that m/z 19,000 and m/z 21,000 peaks of Pueraria could be used for the adulteration analysis and post-translational modification research, demonstrating our method has the potential for broad applications.