Tumor-associated macrophages in anti-PD-1/PD-L1 immunotherapy for hepatocellular carcinoma: recent research progress.

Hepatocellular carcinoma (HCC) is one of the cancers that seriously threaten human health. Immunotherapy serves as the mainstay of treatment for HCC patients by targeting the programmed cell death protein 1/programmed cell death 1 ligand 1 (PD-1/PD-L1) axis. However, the effectiveness of anti-PD-1/PD-L1 treatment is limited when HCC becomes drug-resistant. Tumor-associated macrophages (TAMs) are an important factor in the negative regulation of PD-1 antibody targeted therapy in the tumor microenvironment (TME). Therefore, as an emerging direction in cancer immunotherapy research for the treatment of HCC, it is crucial to elucidate the correlations and mechanisms between TAMs and PD-1/PD-L1-mediated immune tolerance. This paper summarizes the effects of TAMs on the pathogenesis and progression of HCC and their impact on HCC anti-PD-1/PD-L1 immunotherapy, and further explores current potential therapeutic strategies that target TAMs in HCC, including eliminating TAMs in the TME, inhibiting TAMs recruitment to tumors and functionally repolarizing M2-TAMs (tumor-supportive) to M1-TAMs (antitumor type).

Mass spectrometry detection of organophosphorus pesticide adducts on butyrylcholinesterase and albumin.

This study established a method to prepare and detect OPs adducts on butyrylcholinesterase (BChE) and human serum albumin (HSA). OPs (methyl paraoxon, ethyl paraoxon, methyl parathion, parathion) were incubated with BChE or HSA in vitro, and the adducts of OPs-BChE or OPs-HSA were prepared and qualitatively analyzed by ultra-performance liquid chromatography data-dependent high-resolution tandem mass spectrometry (UPLC-ddHRMS/MS). The amounts of BChE and HSA in the incubating systems were varied and the resulting amounts of the adducts were determined using linear regression. OPs-BChE in the blood were isolated by immunomagnetic separation (IMS), and then digested into the OPs-nonapeptide adduct by pepsin. The proteins in the remaining blood plasma were precipitated and digested by pronase to OPs-tyrosines(OPs-Tyr), which were quantified by UPLC-ddHRMS/MS. 4 OPs-nonapeptides and 4 OPs-Tyr adducts were obtained through the process above. The relative mass deviation of incubated adducts between the actual and theoretical exact masses was less than 10 ppm, and further confirmed by fragmentation mass spectra analysis. Calibration curves were linear for all adducts with a coefficient of determination value (R2) ≥0.995. The limits of detection (LOD) and limits of quantification (LOQ) for adducts detected by MS ranged from 0.05 to 1.0 ng/mL, and from 0.1 to 2.0 ng/mL, respectively. The recovery percentages for adducts ranged from 76.1 % to 107.1 %, matrix effects ranged from 83.4 % to 102.1 %. The inter-day and intra-day precision were 6.1-10.1 % and 6.9-12.9 % for adducts. This study provides a new reference method for the detection of organophosphorus pesticide poisoning. In addition, two blood samples with organophosphorus poisoning were tested by the designed method, and the corresponding adducts were detected in both samples.

Predictive model of the efficiency of hematopoietic stem cell collection in patients with multiple myeloma and lymphoma based on multiple peripheral blood markers.

INTRODUCTION: Autologous hematopoietic stem cell transplantation (ASCT) has gained extensive application in the treatment of lymphoma and multiple myeloma (MM). Plenty of studies demonstrate that peripheral blood indicators could be considered potential predictive biomarkers for hematopoietic stem cells (HSCs) collection efficiency, including white blood cell count (WBC), monocyte count (Mono), platelet count (PLT), hematocrit, and hemoglobin levels. Currently, clinically practical predictive models based on these peripheral detection indicators to quickly, conveniently, and accurately predict collection efficiency are lacking. METHODS: In total, 139 patients with MM and lymphoma undergoing mobilization and collection of ASCT were retrospectively studied. The study endpoint was successful collection of autologous HSCs. We analyzed the effects of clinical characteristics and peripheral blood markers on collection success, and screened variables to establish a prediction model. We determined the optimal cutoff value of peripheral blood markers for predicting successful stem cell collection and the clinical value of a multi-marker prediction approach. We also established a prediction model for collection efficacy. RESULTS: Univariate and multivariate logistic regression analyses showed that the mobilization regimen, Mono, PLT, mononuclear cell count (MNC), and peripheral blood CD34+ cell count (PB CD34+ counts) were significant predictors of successful collection of peripheral blood stem cells (PBSC). Two predictive models were constructed based on the results of multivariate logistic analyses. Model 1 included the mobilization regimen, Mono, PLT, and MNC, whereas Model 2 included the mobilization regimen, Mono, PLT, MNC, and PB CD34+ counts. Receiver operating characteristic (ROC) curve analysis showed that the PB CD34+ counts, Model 1, and Model 2 could predict successful HSCs collection, with cutoff values of 26.92 × 106/L, 0.548, and 0.355, respectively. Model 1 could predict successful HSCs collection with a sensitivity of 84.62%, specificity of 75.73%, and area under the curve (AUC) of 0.863. Model 2 could predict successful HSCs collection with a sensitivity of 83.52%, specificity of 94.17%, and AUC of 0.946; thus, it was superior to the PB CD34+ counts alone. CONCLUSION: Our findings suggest that the combination of the mobilization regimen, Mono, PLT, MNC, and PB CD34+ counts before collection has predictive value for the efficacy of autologous HSCs collection in patients with MM and lymphoma. Using models based on these predictive markers may help to avoid over-collection and improve patient outcomes.

Identification of Hypoxia-ALCAMhigh Macrophage- Exhausted T Cell Axis in Tumor Microenvironment Remodeling for Immunotherapy Resistance.

Although hypoxia is known to be associated with immune resistance, the adaptability to hypoxia by different cell populations in the tumor microenvironment and the underlying mechanisms remain elusive. This knowledge gap has hindered the development of therapeutic strategies to overcome tumor immune resistance induced by hypoxia. Here, bulk, single-cell, and spatial transcriptomics are integrated to characterize hypoxia associated with immune escape during carcinogenesis and reveal a hypoxia-based intercellular communication hub consisting of malignant cells, ALCAMhigh macrophages, and exhausted CD8+ T cells around the tumor boundary. A hypoxic microenvironment promotes binding of HIF-1α complex is demonstrated to the ALCAM promoter therefore increasing its expression in macrophages, and the ALCAMhigh macrophages co-localize with exhausted CD8+ T cells in the tumor spatial microenvironment and promote T cell exhaustion. Preclinically, HIF-1ɑ inhibition reduces ALCAM expression in macrophages and exhausted CD8+ T cells and potentiates T cell antitumor function to enhance immunotherapy efficacy. This study reveals the systematic landscape of hypoxia at single-cell resolution and spatial architecture and highlights the effect of hypoxia on immunotherapy resistance through the ALCAMhigh macrophage-exhausted T cell axis, providing a novel immunotherapeutic strategy to overcome hypoxia-induced resistance in cancers.

A pH ultra-sensitive hydrated iridium oxyhydroxide films electrochemical sensor for label-free detection of Vibrio parahaemolyticus.

Vibrio parahaemolyticus (V. parahaemolyticus) is a major foodborne pathogen, which can cause serious foodborne illnesses like diarrhoea. Rapid on-site detection of foodborne pathogens is an ideal way to respond to foodborne illnesses. Herein, we provide an electrochemical sensor for rapid on-site detection. This sensor utilized a pH-sensitive metal-oxide material for the concurrent isothermal amplification and label-free detection of nucleic acids. Based on a pH-sensitive hydrated iridium oxide oxyhydroxide film (HIROF), the electrode transforms the hydrogen ion compound generated during nucleic acid amplification into potential, so as to achieve a real-time detection. The results can be transmitted to a smartphone via Bluetooth. Moreover, HIROF was applied in nucleic acid device detection, with a super-Nernst sensitivity of 77.6 mV/pH in the pH range of 6.0-8.5, and the sensitivity showed the best results so far. Detection of V. parahaemolyticus by this novel method showed a detection limit of 1.0×103 CFU/mL, while the time consumption was only 30 min, outperforming real-time fluorescence loop-mediated isothermal amplification (LAMP). Therefore, the characteristics of compact, portable, and fast make the sensor more widely used in on-site detection.

Combined effects of microplastics and pharmaceutical and personal care products on algae: A critical review.

Microplastics (MPs) and pharmaceuticals and personal care products (PPCPs) are ubiquitous in aquatic environments. Algae play an important role in aquatic environments. Thus, it is important to study the response of algae to combined exposure of MPs and PPCPs. Here, we review the effects of MPs and PPCPs on algae. First, the individual effects of MPs and PPCPs on algae were summarized. Second, the combined effects of MPs and PPCPs on algae were systematically analyzed. (1) Antagonism: ① when the MPs are too large to enter the algal cells, the adsorption of PPCPs onto MPs results in decreased the contact of MPs and PPCPs with algae; ② PPCPs and MPs have opposing actions on the same biological target; ③ MPs increase the activity of metabolic enzymes in algae, thus promoting the PPCP degradation. (2) Synergy: ① when the MPs are small enough to enter algal cells, the adsorption of PPCPs on MPs promotes the entry of PPCPs; ② when MPs are negatively charged, the adsorption of positively charged PPCPs by MPs decreases the electrostatic repulsion, increasing the interaction between algae and MPs; ③ complementary modes of action between MPs and PPCPs show combined effects on the same biological target. Third, the relative importance of the factors that impact the combined effects are evaluated using the random forest model decreased in the following order: PPCP types > algal species > MP size > MP concentration > MP types > exposure time. Finally, future directions for the combined effects of MPs and PPCPs are proposed, which will facilitate a better understanding of the environmental fate and risks of both MPs and PPCPs.

An Energy Efficient and Temperature Stable Digital FLL-based Wakeup Timer with Time-Domain Temperature Compensation.

This brief presents an on-chip digital intensive frequency-locked loop (DFLL)-based wakeup timer with a time-domain temperature compensation featuring a embedded temperature sensor. The proposed compensation exploits the deterministic temperature characteristics of two complementary resistors to stabilize the timer's operating frequency across the temperature by modulating the activation time window of the two resistors. As a result, it achieves a fine trimming step (± 1 ppm), allowing a small frequency error after trimming (<± 20 ppm). By reusing the DFLL structure, instead of employing a dedicated sensor, the temperature sensing operates in the background with negligible power (2 %) and hardware overhead (< 1 %). The chip is fabricated in 40 nm CMOS, resulting in 0.9 pJ/cycle energy efficiency while achieving 8 ppm/ºC from -40ºC to 80ºC.

Human cytomegalovirus infection impairs neural differentiation via repressing sterol regulatory element binding protein 2-mediated cholesterol biosynthesis.

Congenital human cytomegalovirus (HCMV) infection is a major cause of abnormalities and disorders in the central nervous system (CNS) and/or the peripheral nervous system (PNS). However, the complete pathogenesis of neural differentiation disorders caused by HCMV infection remains to be fully elucidated. Stem cells from human exfoliated deciduous teeth (SHEDs) are mesenchymal stem cells (MSCs) with a high proliferation and neurogenic differentiation capacity. Since SHEDs originate from the neural crest of the early embryonic ectoderm, SHEDs were hypothesized to serve as a promising cell line for investigating the pathogenesis of neural differentiation disorders in the PNS caused by congenital HCMV infection. In this work, SHEDs were demonstrated to be fully permissive to HCMV infection and the virus was able to complete its life cycle in SHEDs. Under neurogenic inductive conditions, HCMV infection of SHEDs caused an abnormal neural morphology. The expression of stem/neural cell markers was also disturbed by HCMV infection. The impairment of neural differentiation was mainly due to a reduction of intracellular cholesterol levels caused by HCMV infection. Sterol regulatory element binding protein-2 (SREBP2) is a critical transcription regulator that guides cholesterol synthesis. HCMV infection was shown to hinder the migration of SREBP2 into nucleus and resulted in perinuclear aggregations of SREBP2 during neural differentiation. Our findings provide new insights into the prevention and treatment of nervous system diseases caused by congenital HCMV infection.

Low Macular Pigment Optical Density Is Associated with Manifest Primary Open-Angle Glaucoma in Older Women.

Background: Lower density of carotenoids lutein and zeaxanthin (L/Z) in the macula (i.e., macular pigment) has been linked to greater risk for age-related eye disease. Objectives: We evaluated whether macular pigment optical density (MPOD) was associated with manifest primary open-angle glaucoma (POAG) among older women in the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2). Methods: MPOD was measured with customized heterochromatic flicker photometry in women who attended CAREDS2 (2016-2019) and CAREDS1 (2001-2004) study visits. Manifest POAG at CAREDS2 was assessed using visual fields, disc photos, optical coherence tomography, and medical records. Age-adjusted linear and logistic regression models were used to investigate the cross-sectional association between POAG and MPOD at CAREDS2, and MPOD measured 15 years earlier at CAREDS1. Results: Among 426 CAREDS2 participants (mean age: 80 y; range: 69-98 y), 26 eyes with manifest POAG from 26 participants were identified. Glaucomatous eyes had 25% lower MPOD compared to nonglaucomatous eyes [mean (SE): 0.40 (0.05) compared with 0.53 (0.01)] optical density units (ODU), respectively (P = 0.01). Compared with MPOD quartile 1, odds for POAG were lower for women in quartiles 2-4 (P-trend = 0.01). After excluding eyes with age-related macular degeneration, associations were similar but not statistically significant (P-trend = 0.16). Results were similar for MPOD measured at CAREDS1. Conclusions: Our results add to growing evidence that low MPOD may be a novel glaucoma risk factor and support further studies to assess the utility of dietary interventions for glaucoma prevention.

HIV associated lymphoma: latest updates from 2023 ASH annual meeting.

The incidence, clinical characteristics, and prognostic factors of HIV-associated lymphoma remain poorly defined compared to HIV-negative lymphoma. Currently, there are no standard guidelines for treatment of these patients. We summarized several latest reports of HIV associated lymphoma from the 2023 ASH Annual Meeting (ASH2023).

Activation of TAS2R4 signaling attenuates podocyte injury induced by high glucose.

Bitter taste receptors (TAS2Rs) Tas2r108 gene possesses a high abundance in mouse kidney; however, the biological functions of Tas2r108 encoded receptor TAS2Rs member 4 (TAS2R4) are still unknown. In the present study, we found that mouse TAS2R4 (mTAS2R4) signaling was inactivated in chronic high glucose-stimulated mouse podocyte cell line MPC, evidenced by the decreased protein expressions of mTAS2R4 and phospholipase C ß2 (PLCß2), a key downstream molecule of mTAS2R4 signaling. Nonetheless, agonism of mTAS2R4 by quinine recovered mTAS2R4 and PLCß2 levels, and increased podocyte cell viability as well as protein expressions of ZO-1 and nephrin, biomarkers of podocyte slit diaphragm, in high glucose-cultured MPC cells. However, blockage of mTAS2R4 signaling with mTAS2R4 blockers γ-aminobutyric acid and abscisic acid, a Gßγ inhibitor Gallein, or a PLCß2 inhibitor U73122 all abolished the effects of quinine on NLRP3 inflammasome and p-NF-κB p65 as well as the functional podocyte proteins in MPC cells in a high glucose condition. Furthermore, knockdown of mTAS2R4 with lentivirus-carrying Tas2r108 shRNA also ablated the effect of quinine on the key molecules of the above inflammatory signalings and podocyte functions in high glucose-cultured MPC cells. In summary, we demonstrated that activation of TAS2R4 signaling alleviated the podocyte injury caused by chronic high glucose, and inhibition of NF-κB p65 and NLRP3 inflammasome mediated the protective effects of TAS2R4 activation on podocytes. Moreover, activation of TAS2R4 signaling could be an important strategy for prevention and treatment of diabetic kidney disease.

Isaridin E Protects against Sepsis by Inhibiting Von Willebrand Factor-Induced Endothelial Hyperpermeability and Platelet-Endothelium Interaction.

Endothelial hyperpermeability is pivotal in sepsis-associated multi-organ dysfunction. Increased von Willebrand factor (vWF) plasma levels, stemming from activated platelets and endothelium injury during sepsis, can bind to integrin αvß3, exacerbating endothelial permeability. Hence, targeting this pathway presents a potential therapeutic avenue for sepsis. Recently, we identified isaridin E (ISE), a marine-derived fungal cyclohexadepsipeptide, as a promising antiplatelet and antithrombotic agent with a low bleeding risk. ISE's influence on septic mortality and sepsis-induced lung injury in a mouse model of sepsis, induced by caecal ligation and puncture, is investigated in this study. ISE dose-dependently improved survival rates, mitigating lung injury, thrombocytopenia, pulmonary endothelial permeability, and vascular inflammation in the mouse model. ISE markedly curtailed vWF release from activated platelets in septic mice by suppressing vesicle-associated membrane protein 8 and soluble N-ethylmaleide-sensitive factor attachment protein 23 overexpression. Moreover, ISE inhibited healthy human platelet adhesion to cultured lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), thereby significantly decreasing vWF secretion and endothelial hyperpermeability. Using cilengitide, a selective integrin αvß3 inhibitor, it was found that ISE can improve endothelial hyperpermeability by inhibiting vWF binding to αvß3. Activation of the integrin αvß3-FAK/Src pathway likely underlies vWF-induced endothelial dysfunction in sepsis. In conclusion, ISE protects against sepsis by inhibiting endothelial hyperpermeability and platelet-endothelium interactions.

Analysis of the lipidomic profile of vegetable oils and animal fats and changes during aging by UPLC-Q-exactive orbitrap mass spectrometry.

Vegetable oil and animal fat residues are common evidence in the cases of homicide, arson, theft, and other crimes. However, the lipid composition and content changes during aging on complex carriers remain unclear. Therefore, this study dynamically monitored the lipid composition and content changes during aging of 13 different types of vegetable oils and animal fats on five different carriers using the UPLC-Q-Exactive Orbitrap MS method. A total of 6 subclasses of 93 lipids including lysophosphatidylcholine (2 species), phosphatidylcholine (2 species), diglyceride (5 species), triglyceride (81 species), acylGlcCampesterol ester (2 species), and acylGlcSitosterol ester (1 species), were first identified in fresh vegetable oils and animal fats. By comparing the LC-MS/MS chromatograms of fresh vegetable oils and animal fats, it was found that there were significant differences between the chromatograms of vegetable oils and animal fats, but it was difficult to distinguish between the chromatograms of vegetable oils or animal fats. After aging at 60 °C for 200 days, there was a significant decrease in the content of diglyceride, triglyceride, acylGlcCampesterol ester, and acylGlcSitosterol ester, while the content of lysophosphatidylcholine and phosphatidylcholine initially increased and then decreased. Furthermore, statistical analysis of lipid differences between vegetable oils and animal fats was performed using cluster heat maps, volcanic maps, PCA, and OPLS-DA. On average, 33 significantly different lipids were screened (VIP > 1, p < 0.05), which could serve as potential biomarkers for distinguishing vegetable oils and animal fats. It was found that the potential biomarkers still existed during aging of vegetable oils and animal fats (100 and 200 days). This research provides important reference information for the identification of vegetable oil and animal fat residues in complex carriers at crime scenes.

"I feel like I'm walking on eggshells": a qualitative study of moral distress among Chinese emergency doctors.

BACKGROUND: While the number of emergency patients worldwide continues to increase, emergency doctors often face moral distress. It hampers the overall efficiency of the emergency department, even leading to a reduction in human resources. AIM: This study explored the experience of moral distress among emergency department doctors and analyzed the causes of its occurrence and the strategies for addressing it. METHOD: Purposive and snowball sampling strategies were used in this study. Data were collected through in-depth, semi-structured interviews with 10 doctors working in the emergency department of a tertiary general hospital in southwest China. The interview data underwent processing using the Nvivo 14 software. The data analysis was guided by Colaizzi's phenomenological analysis method. STUDY FINDINGS: This study yielded five themes: (1) imbalance between Limited Medical Resources and High-Quality Treatment Needs; (2) Ineffective Communication with Patients; (3) Rescuing Patients With no prospect of treatment; (4) Challenges in Sustaining Optimal Treatment Measures; and (5) Strategies for Addressing Moral Distress. CONCLUSION: The moral distress faced by emergency doctors stems from various aspects. Clinical management and policymakers can alleviate this distress by enhancing the dissemination of emergency medical knowledge to the general public, improving the social and economic support systems, and strengthening multidisciplinary collaboration and doctors' communication skills.

The Effects of WeChat-Based Teach-Back Health Education on Patients With Advanced Cancer Pain.

BACKGROUND: Providing effective health education is essential for patients with cancer-related pain. One solution is leveraging instant messaging tools for teach-back health education. OBJECTIVES: This study investigated the effects of WeChat-based teach-back health education on patients with advanced cancer who underwent patient-controlled intrathecal analgesia implantation and used hydromorphone. METHODS: This retrospective study evaluated 150 hospitalized patients with advanced cancer pain. Patients were classified into a conventional health education group (N = 50) and a teach-back group (N = 100) based on whether they received WeChat-based teach-back health education. Pain was rated using a numeric rating scale, and sleep quality was measured using the Pittsburgh Sleep Quality Index at one, two, and three months postdischarge. FINDINGS: Patients who received remote teach-back health education better managed their pain. Data also demonstrated improvements in patients' sleep quality and caregiver satisfaction, and reductions in the occurrence of adverse reactions.

Single-atom Mn sites confined into hierarchically porous core-shell nanostructures for improved catalysis of oxygen reduction.

Applications of zinc-air batteries are partially limited by the slow kinetics of oxygen reduction reaction (ORR); Thus, developing effective strategies to address the compatibility issue between performance and stability is crucial, yet it remains a significant challenge. Here, we propose an in situ gas etching-thermal assembly strategy with an in situ-grown graphene-like shell that will favor Mn anchoring. Gas etching allows for the simultaneous creation of mesopore-dominated carbon cores and ultrathin carbon layer shells adorned entirely with highly dispersed Mn-N4 single-atom sites. This approach effectively resolves the compatibility issue between activity and stability in a single step. The unique core-shell structure allows for the full exposure of active sites and effectively prevents the agglomerations and dissolution of Mn-N4 sites in cores. The corresponding half-wave potential for ORR is up to 0.875 V (vs. reversible hydrogen electrode (RHE)) in 0.1 M KOH. The gained catalyst (Mn-N@Gra-L)-assembled zinc-air battery has a high peak power density (242 mW cm-2) and a durability of âˆ¼ 115 h. Furthermore, replacing the zinc anode achieved a stable cyclic discharge platform of âˆ¼ 20 h at varying current densities. Forming more fully exposed and stable existing Mn-N4 sites is a governing factor for improving the electrocatalytic ORR activity, significantly cycling durability, and reversibility of zinc-air batteries.

Adjuvant donafenib for hepatocellular carcinoma patients at high-risk of recurrence after radical resection: a real-world experience.

Background: Adjuvant therapy is used to reduce the risk of hepatocellular carcinoma (HCC) recurrence and improve patient prognosis. Exploration of treatment strategies that are both efficacious and safe has been extensively performed in the recent years. Although donafenib has demonstrated good efficacy in the treatment of advanced HCC, its use as adjuvant therapy in HCC has not been reported. Objectives: To investigate the efficacy and safety of postoperative adjuvant donafenib treatment in patients with HCC at high-risk of recurrence. Design: Retrospective study. Methods: A total of 196 patients with HCC at high-risk of recurrence were included in this study. Of these, 49 received adjuvant donafenib treatment, while 147 did not. Survival outcomes and incidence of adverse events (AEs) in the donafenib-treated group were compared. Inverse probability of treatment weighting (IPTW) method was used. Results: The median follow-up duration was 21.8 months [interquartile range (IQR) 17.2-27.1]. Before IPTW, the donafenib-treated group exhibited a significantly higher 1-year recurrence-free survival (RFS) rate (83.7% versus 66.7%, p = 0.023) than the control group. Contrarily, no significant difference was observed in the 1-year overall survival (OS) rates between the two groups (97.8% versus 91.8%, p = 0.120). After IPTW, the 1-year RFS and OS rates (86.6% versus 64.8%, p = 0.004; 97.9% versus 89.5%, p = 0.043, respectively) were higher than those in the control group. Multivariate analysis revealed that postoperative adjuvant donafenib treatment was an independent protective factor for RFS. The median duration of adjuvant donafenib treatment was 13.6 (IQR, 10.7-18.1) months, with 44 patients (89.8%) experienced AEs, primarily grade 1-2 AEs. Conclusion: Postoperative adjuvant donafenib treatment effectively reduced early recurrence among patients with HCC at high-risk of recurrence, while exhibiting favorable safety and tolerability profile. However, these findings warrant further investigation.

Comparison of the outcomes of patients with HCC with or without donafenib after radical resection to better understand the efficacy and safety of postoperative adjuvant donafenib Why was this study done? Donafenib is the only new-generation targeted drug developed in the past 14 years that has demonstrated superior efficacy and increased safety in the first-line treatment of HCC. We aimed to explore whether postoperative adjuvant donafenib can improve the prognosis of patients with HCC at high-risk of recurrence. What did the researchers do? Medical data of patients with HCC at high-risk of recurrence who underwent radical resection at two medical centers between April 2021 and October 2022 were collected to compare long-term outcomes of patients treated with and without donafenib and explore the safety of adjuvant donafenib treatment. What did the researchers find? A total of 196 patients with HCC at high-risk of recurrence, including 49 who received adjuvant donafenib treatment and 147 who did not, were analyzed. At a median follow-up of 21.8 months, it was observed that adjuvant donafenib treatment effectively reduced early recurrence among patients with HCC at high-risk of recurrence, while exhibiting favorable safety and compliance profiles. What do the findings mean? The study provides real-world clinical empirical data on adjuvant donafenib treatment for patients with HCC at high-risk of recurrence, and these results may provide new directions for adjuvant treatment of HCC.

A Hydration Model to Evaluate the Properties of Cement-Quartz Powder Hybrid Concrete.

Although quartz powder is a common concrete filling material, the importance and originality of this study lies in the development of a hydration model for quartz powder-cement binary mixtures and the adoption of this model to predict the development of concrete material properties. The purpose of this study is to use this model to promote the material design of environmentally friendly concrete and to elucidate the relationships in the development of the various properties of quartz powder concrete. The method used in this study was as follows: The parameters of the hydration model were obtained through seven days of hydration heat experiments. The hydration heat up to 28 days was also calculated, and the various properties of the concrete were predicted from the heat of hydration. The main findings of this study were as follows: (1) The ultimate hydration heat released per gram of cement for the different quartz powder substitution rates and quartz powder particle fineness was the same, at 390.145 J/g cement, as was the shape index of the hydration model at -1.003. (2) Moreover, through the model calculations, we found that, at the twenty-eighth day of the curing period for the quartz powder specimens with different quartz powder substitution amounts and different fineness, the reaction level of the cement was similar, at 0.963, as were the values of the cumulative heat of hydration, with both at 375.5 J/g cement. (3) The model showed that, in the late stage (28 days) of hydration for quartz powders of different fineness and when the substitution amount was the same, the cumulative heat of hydration over 28 days was similar. (4) The properties of concrete were evaluated using the calculated hydration heat. Overall, the predictive performance of the power and linear functions was similar, with no significant differences being found.

Sequencing-induced artefacts in NGS STR data.

Significant progress has been made in recent years in the development of techniques for Next Generation Sequencing (NGS), or Massively Parallel Sequencing (MPS), of forensically relevant short tandem repeat (STR) loci. However, as these technologies are investigated and adopted by forensic laboratories, new challenges unfold that require further scrutiny. In the analysis of DNA profiles generated using the MiSeq FGx sequencing system, we have observed noise sequences with relatively high readcounts that are challenging to distinguish from genuine alleles. These high read count noise sequences appear as allele sequences with one or a few substituted bases compared to a known allele sequence within the profile. An examination of ForenSeq DNA Signature Prep Kit STR noise sequences revealed that the substituted base of a parent allele can align to the same position on the sequence across noise sequences. This suggests that these substitution events occur at specific positions within the amplicon, resulting in multiple noise reads with substitutions at the same position. Mapping of the noise events onto the original raw read positions revealed a high number of events, or "noise spikes", occurring at specific positions within a given sequencing run. These noise spikes affected reads across the entire run, agnostic of locus or sample, while the position, occurrence, and amplitude of the spikes differed across runs. The majority of noise sequences with high read counts in a DNA profile were generated from base changes at these spike positions, and could be classified as "noise spike artefacts". In this paper we present evidence of the noise spike artefacts and their genesis during the sequencing process in the sequencing-by-synthesis (SBS) cycles, as well as the methods developed to detect them. The information and methods will assist laboratories with detecting noise spikes in MiSeq FGx sequencing runs, differentiating authentic allele sequences from noise spike artefacts, and developing protocols for analyst review and handling of MiSeq FGx data.