Microbial Upcycling of Depolymerized Lignin into Value-Added Chemicals.

Lignin is one of the most widespread organic compounds found on earth, boasting a wealth of aromatic molecules. The use of lignin feedstock for biochemical productions is of great importance for achieving "carbon neutrality." In recent years, a strategy for lignin valorization known as the "bio-funnel" has been proposed as a means to generate a variety of commercially valuable chemicals from lignin-derived compounds. The implementation of biocatalysis and metabolic engineering techniques has substantially advanced the biotransformation of depolymerized lignin into chemicals and materials within the supply chain. In this review, we present an overview of the latest advancements in microbial upcycling of depolymerized lignin into value-added chemicals. Besides, the review provides insights into the problems facing current biological lignin valorization while proposing further research directions to improve these technologies for the extensive accomplishment of the lignin upcycling.

ERBB2 is a potential diagnostic and prognostic biomarker in renal clear cell carcinoma.

Renal clear cell carcinoma (ccRCC) is a common parenchymal tumor of the kidney, and the discovery of biomarkers for early and effective diagnosis of ccRCC can improve the early diagnosis of patients and thus improve long-term survival. Erb-b2 receptor tyrosine kinase 2 (ERBB2) mediates the processes of cell proliferation, differentiation, and apoptosis inhibition. The purpose of this study was to investigate the diagnostic and prognostic role of ERBB2 in ccRCC. We analyzed the expression levels of ERBB2 in various cancers from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. RNA-seq data were analyzed using R packages to identify differentially expressed genes between the high and low ERBB2 expression groups in the TCGA-KIRC dataset. Spearman correlation analysis was performed to determine the correlation between ERBB2 expression and immune cell infiltration, immune checkpoint expression, and PTEN expression. DNA methylation changes and genetic alterations in ERBB2 were assessed using the MethSurv and cBioPortal databases. Logistic regression analysis was performed to determine the correlation between ERBB2 expression and the clinicopathological characteristics of ccRCC patients. The diagnostic and prognostic value of ERBB2 was assessed using Kaplan‒Meier (K‒M) survival curves, diagnostic ROC curves, time-dependent ROC curves, nomogram models, and Cox regression models. The expression level of ERBB2 is lower in tumor tissues of ccRCC patients than in the corresponding control tissues. Differentially expressed genes associated with ERBB2 were significantly enriched in the pathways "BMP2WNT4FOXO1 pathway in primary endometrial stromal cell differentiation" and "AMAN pathway". In ccRCC tissues, ERBB2 expression levels were associated with immune cell infiltration, immune checkpoints, and PTEN. The DNA methylation status of 10 CpG islands in the ERBB2 gene was associated with the prognosis of ccRCC. ERBB2 expression levels in ccRCC tissues were associated with race, sex, T stage, M stage, histological grade, and pathological stage. Cox regression analysis showed that ERBB2 was a potential independent predictor of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in ccRCC patients. ROC curve analysis showed that the expression level of ERBB2 could accurately distinguish between ccRCC tissue and adjacent normal renal tissue. Our study showed that ERBB2 expression in ccRCC tissues can be of clinical importance as a potential diagnostic and prognostic biomarker.

Research progress on measurement methods and evaluation of the hemodialysis adequacy index Kt/V.

The most common form of replacement therapy for end-stage renal disease (ESRD) is hemodialysis, and the adequacy of hemodialysis is strongly associated with the quality of life and long-term survival of patients. Kt/V is currently one of the most important indicators for evaluating the adequacy of hemodialysis. There are many methods for measuring Kt/V, such as blood collection and measurement, dialysate measurement, bioresistive resistance, WinNonlin software analysis, and artificial intelligence. There are different views on the importance of Kt/V as an indicator of the adequacy of hemodialysis. This article provides a literature review of the various methods of measuring Kt/V and on different perspectives on Kt/V as an evaluation of hemodialysis adequacy.

Development of puerarin-loaded poly(lactic acid) microspheres for sustained ocular delivery: In vitro/vivo evaluation.

Diabetic retinopathy, an ocular complication of diabetes, is an important cause of blindness in adults. Puerarin is considered to have promising potential for clinical use in treating diabetic retinopathy. In this study, we designed a novel puerarin-loaded poly(lactic acid) sustained-release microspheres suitable for ocular administration, and we assessed itsin vitro and in vivo properties. The preparation of puerarin-loaded microspheres was optimized by Box-Behnken response surface design. The encapsulation efficiency and drug loading of microspheres were 35.71% and 3.85%, respectively. The microspheres exhibited good dispersion and high safety, making it suitable for ocular drug delivery. In vitro release demonstrated that microspheres had a well-sustained release effectiveness, and its release behavior complied with the zero-order kinetic characteristics. The results of ocular tissue distribution revealed that the CmaxandAUC0-∞ of the microspheres group in the retina and choroid were considerably higher than those of the solution group and the intravenous injection group. This research revealed that intravitreal injection of microspheres can significantly prolong the half-life of puerarin in eye tissues and achieve sustained drug release. Therefore, intravitreal injection of microspheres has positive implications for the treatment of diabetic retinopathy.

Microalgae-bacterial consortiums for enhanced degradation of nonylphenol: Biodegradability and kinetic analysis.

The widespread use of non-ionic surfactant nonylphenol (NP) has led to significant water pollution, posing a threat to both ecological stability and human health. However, the efficient biodegradation method and system of NP-biodegradation remain complex scientific challenges. In this study, we isolated and characterized three Pseudomonas sp. strains SW-1 (Scenedesmus quadricauda-associated), ZL-2 (Ankistrodesmus acicularis-associated), XQ-3 (Chlorella vulgaris-associated), and one NP-degrading Cupriavidus sp. strain EB-4, which exhibited the ability to utilize NP as the sole carbon source. Furthermore, four consortiums of microalgae-bacterial, S. quadricauda and SW-1 (S-SW), A. acicularis and ZL-2 (A-ZL), C. vulgaris and XQ-3 (C-XQ), S. quadricauda and EB-4 (S-EB), were constructed to investigate their biodegradability and kinetic characteristics of NP degradation from water. The consortiums showed higher degradation efficiency compared to individual microalgae or bacteria. The C-XQ consortium exhibited the highest degradation rate, removing over 94% of NP within just seven days. The first-order model with the following order of degradation rate by consortiums was C-XQ (0.3960 d-1) > S-SW (0.3506 d-1) > A-ZL (0.1968 d-1) > S-EB (0.1776 d-1). Compared with the results of our previous study, the interaction between microalgae and bacteria is not a simple additive relationship. Our findings highlight the potential of an algal-bacterial consortium for the remediation of NP-contaminated environments.

Foliar spraying exogenous ABA resists chilling stress on adzuki beans (Vigna angularis).

Adzuki bean, an important legume crop, exhibits poor tolerance to low temperatures. To investigate the effect of exogenous abscisic acid (ABA) on the physiological metabolism and yield resistance of adzuki bean under low-temperature stress, we conducted a potted experiment using Longxiaodou 4 (LXD 4) and Tianjinhong (TJH) as test materials and pre-sprayed with exogenous ABA at flowering stage continuously for 5 days with an average of 12°C and an average of 15°C, respectively. We found that, compared with spraying water, foliar spraying exogenous ABA increased the activities of antioxidants and the content of non-enzymatic antioxidants, effectively inhibited the increase of malondialdehyde (MDA), hydrogen peroxide (H2O2) content, O2-· production rate. Exogenous ABA induced the activation of endogenous protective mechanisms by increasing antioxidant enzymes activities such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), as well as elevated levels of non-enzymatic antioxidants including ascorbic acid (ASA) and glutathione (GSH). Moreover, the yield loss of 5.81%-39.84% caused by chilling stress was alleviated by spraying ABA. In conclusion, foliar spraying exogenous ABA can reduce the negative effects of low-temperature stress on the yield of Adzuki beans, which is essential to ensure stable production of Adzuki beans under low-temperature conditions.

Fruquintinib in metastatic colorectal cancer: a multicenter real-world analysis on efficacy, safety, and predictive and prognostic factors.

Background: Randomized trials have shown a survival benefit for fruquintinib over placebo in patients with metastatic colorectal cancer (mCRC) that progressed after standard therapies, but real-world prognostic analyses have been seldom reported. We evaluated survival, safety outcomes, and predictive and prognostic factors in patients treated with fruquintinib in a real-life setting. Methods: We conducted a multi-center study by collecting relevant data on patients with advanced colorectal cancer (CRC) who received fruquintinib, focusing on progression-free survival (PFS), overall survival (OS), and L3 skeletal muscle index (SMI), including safety follow-up. Results: From January 2020 to January 2022, a total of 140 patients were selected and included in this study. The cut-off date was 30 July 2022. The median follow-up time was 18.3 months (range, 6-29.3 months) and the median age of included cases was 63 years (range, 32-81 years). The median PFS and OS for the 140 patients was 6.3 and 12.6 months, respectively. The median PFS and OS for the 76 patients who were included in SMI analysis was 6.0 and 12.0 months, respectively. Multivariate analysis suggested brain metastasis {hazard ratio (HR) [95% confidence interval (CI)]: 2.779 (1.162-6.646), P=0.02}, decrease in SMI of >5% [HR (95% CI): 9.732 (2.201-43.028), P=0.003], and baseline carcinoembryonic antigen (CEA) level [HR (95% CI): 4.061 (1.391-11.858), P=0.01] as independent predictors of OS. The most common treatment-related adverse events (TRAEs) were hypertension (24, 17.1%), fatigue (21, 15%), and hand-foot syndrome (20, 14.3%); 9 (13.6%) and 15 (10.7%) patients had dose reduction and treatment discontinuation due to TRAEs respectively. Conclusions: The real-world efficacy and safety of fruquintinib in advanced CRC patients are numerically superior to that in the previous phase III studies. SMI, brain metastasis and CEA could serve as potential markers for patient selection.

Oilseed flax cultivation: optimizing phosphorus use for enhanced growth and soil health.

Introduction: Oilseed flax (Linum usitatissimum L.) yields are phosphate (P) fertilizer-limited, especially in the temperate semiarid dryland regions of North China. However, there are limited studies on the effects of P-fertilizer inputs on plant growth and soil microorganisms in flax planting systems. Methods: To address this gap, a field experiment was conducted with four treatments: no P addition and application of 40, 80, and 120 kg P ha-¹, respectively. The aim was to investigate the influence of various P fertilizer inputs on yield, plant dry matter, P use efficiency, as well as the population of soil arbuscular mycorrhizal fungi (AMF) and bacteria in dryland oilseed flax. Results: Our results show that the P addition increased the dry matter, and the yield of oilseed increased by ~200% at 120 kg P ha-1 addition with inhibition on the growth of AMF hyphae. The moderate P supply (80 kg ha-1) was adequate for promoting P translocation, P use efficiency, and P recovery efficiency. Soil pH, available P, and available K significantly (p< 0.05) promoted the abundance of the dominant taxa (Acidobacteria_GP6, Sphingobacteria and Bacteroidetes). In addition, it is imperative to comprehend the mechanism of interaction between phosphorus-fertilizer inputs and microbiota in oilseed flax soil. Discussion: This necessitates further research to quantify and optimize the moderate phosphorus supply, regulate soil microbes to ensure high phosphorus utilization, and ultimately establish a sustainable system for oilseed flax cultivation in the local area.

Compact Chromatic Confocal Lens with Large Measurement Range.

Spectral confocal sensors are effective for measuring displacements. The core of the spectral confocal measurement system is a dispersive objective lens that uses optical dispersion to establish a one-to-one correspondence between the focusing position and wavelength, achieving high-resolution measurements in the longitudinal direction. Despite significant progress in dispersive objective lenses for spectral confocal sensor systems, challenges such as a limited dispersion range, high cost, and insufficient measurement accuracy persist. To expand the measurement range and improve the accuracy of the spectral confocal sensor, we designed a compact, long-axial dispersion objective lens. This lens has a simple structure that requires only six lens elements, two of which form cemented doublets. The system length is 58 mm, with a working distance of 46 ± 6 mm and a dispersion range of 12 mm within the wavelength range of 450-656 nm. The lens has an object-side numerical aperture (NA) of 0.22 and an image-side NA between 0.198 and 0.24, ensuring high light energy utilization. Finally, a spectral confocal measurement system was constructed based on the designed dispersive objective lens, and performance evaluation tests were conducted. The test results showed that the system achieved a resolution of 0.15 µm and a maximum linear error of ±0.7 µm, demonstrating high-precision measurement capabilities. The proposed lens design enables the development of more portable and cost-effective spectral confocal sensors.

Engineered Extracellular Vesicle-Based Nanoformulations That Coordinate Neuroinflammation and Immune Homeostasis, Enhancing Parkinson's Disease Therapy.

Although conventional intervention to microglia can mitigate neuroinflammation in the short term, immune disorders by peripheral inflammatory cells can infiltrate continuously, resulting in an overactivated immune microenvironment of Parkinson's disease (PD). Here, we design engineered extracellular vesicle-based nanoformulations (EVNs) to address multiple factors for the management of PD. Specifically, EVN is developed by coating CCR2-enriched mesenchymal stem cell-derived extracellular vesicles (MSCCCR2 EVs) onto a dihydrotanshinone I-loaded nanocarrier (MSeN-DT). The MSCCCR2 EVs (the shell of EVN) can actively show homing to specific chemokines CCL2 in the substantia nigra, which enables them to block the infiltration of peripheral inflammatory cells. Interestingly, MSeN-DT (the core of EVN) can promote the Nrf2-GPX4 pathway for the suppression of the source of inflammation by inhibiting ferroptosis in microglia. In the PD model mice, a satisfactory therapeutic effect is achieved, with inhibition of peripheral inflammatory cell infiltration, precise regulation of inflammatory microglia in the substantia nigra, as well as promotion of behavioral improvement and repairing damaged neurons. In this way, the combinatorial code of alleviation of inflammation and modulation of immune homeostasis can reshape the immune microenvironment in PD, which bridges internal anti-inflammatory and external immunity. This finding reveals a comprehensive therapeutic paradigm for PD that breaks the vicious cycle of immune overactivation.

Feasibility and long-term survival of proximal gastrectomy after neoadjuvant therapy for locally advanced proximal gastric cancer: A propensity-score-matched analysis.

BACKGROUND: Neoadjuvant therapy enhances the possibility of achieving radical resection and improves the prognosis for locally advanced gastric cancer (GC). However, there is a lack of evidence regarding the optimal extent of resection for locally advanced proximal GC after neoadjuvant therapy. METHODS: In this study, 330 patients underwent resection in Peking University Cancer Hospital, with curative intent after neoadjuvant therapy for histologically confirmed proximal GC from January 2009 to December 2022. Among them, 45 patients underwent proximal gastrectomy (PG), while 285 underwent total gastrectomy (TG). RESULTS: In this study, 45 patients underwent proximal gastrectomy (PG), while 285 underwent total gastrectomy (TG). After propensity-score matching, 110 patients (71 TG and 39 PG) were included in the analysis. No significant differences between PG and TG regarding short-term outcomes and long-term prognosis were found. Specifically, PG demonstrated comparable overall survival to TG (P = 0.47). Subgroup analysis revealed that although not statistically significant, PG showed a potential advantage over TG in overall survival for patients with tumor-long diameters less than 4 cm (P = 0.31). However, for those with a long diameter larger than 4 cm, TG had a better survival probability (P = 0.81). No substantial differences were observed in baseline characteristics, surgical safety, postoperative recovery, and postoperative complications. CONCLUSION: For locally advanced proximal GC with objective response to neoadjuvant therapy (long diameter <4 cm), PG is an alternative surgical procedure. Further research and prospective studies are warranted to validate these findings and guide clinical decision-making.

Design and Evaluation of Ophthalmic Thermosensitive In Situ Gel of Compound Salvia.

The compound Salvia Recipe has been shown to have a relatively significant curative effect in management of cardiovascular and cerebrovascular diseases. This work aimed to prepare a thermosensitive in situ gel (ISG) delivery system that utilizes Poloxamer 407, Poloxamer 188, and hydroxypropyl methylcellulose for ocular administration of the compound Salvia recipe to treat cardiovascular and cerebrovascular diseases. The central composite design-response surface method was utilized to improve the prescription of the gel. The formulated gel was characterized and assessed in terms of stability, retention time, in vitro release, rheology, ocular irritation, pharmacokinetics studies, and tissue distribution. The gel was a liquid solution at room temperature and became semisolid at physiological temperature, prolonging its stay time in the eye. Pharmacokinetics and tissue distribution experiments indicated that thermosensitive ISG had enhanced targeting of heart and brain tissues. Additionally, it could lower drug toxicity and side effects in the lungs and kidneys. The compound Salvia ophthalmic thermosensitive ISG is a promising drug delivery system for the management of cardiovascular and cerebrovascular illnesses.

Eco-friendly, highly interpenetrated and slightly swollen pHEMA hydrogel foam for durable underwater superoleophobicity and emulsion separation.

Despite the emergence of hydrogels as ideal candidates for preparing the superhydrophilic materials for emulsion separation, their structural stability and swelling still hinder their long-term use, mainly due to structure defects after swelling. Herein, differing from the common modification, the eco-friendly poly 2-hydroxyethyl methacrylate (pHEMA) hydrogel foam was designed and synthesized via a one-step strategy by using the high internal phase emulsion (HIPE) template method, which endowed it with a highly interpenetrated porous structure. Unlike the normal swellable hydrogels such as poly(N-isoproplyacrylamide) (PNIPAM) hydrogel, or modified hydrogel coatings, the pHEMA hydrogel foam displayed stable structure and underwater superoleophobicity after 20 d of immersion in water. The pHEMA hydrogel foam could separate different kinds of highly surfactant-stabilized oil-in-water (O/W) emulsions with a high separation efficiency of 99.3% for liquid paraffin emulsion obtained solely under gravity-driven. Additionally, it exhibited excellent antifouling performance and long-term acid/alkali tolerance over 100 h without decrease in emulsion separation efficiency (98.0%, oil/water ratio of 99:1) and permeation flux (over 2000 L·m-2·h-1) attributed to its stable bulky structure. Moreover, the pHEMA hydrogel foam demonstrated high cell viability of 96.87% and 95.96% after culturing the 3T3 clone A31 cells in the pHEMA hydrogel foam for 24 h and 48 h, respectively, indicating good biocompatibility. Hence, our work provides a new design to develop an eco-friendly bulk hydrogel foam that achieves stable structure and performance for emulsion separation.

A cellular senescence-related signature for predicting prognosis, immunotherapy response, and candidate drugs in patients treated with transarterial chemoembolization (TACE).

BACKGROUND: Cellular senescence is essential to TME development, progression, and remodeling. Few studies have examined cellular senescence in HCC after TACE. Investigating the relationship between cellular senescence, post-TACE prognosis, the TME, and immune treatment responses is crucial. METHODS: We analyzed the GSE104580 dataset to identify DEGs. A cellular senescence-related signature was developed using LASSO Cox regression in the GSE14520 dataset and validated in the ICGC dataset. High- and low-risk subgroups were compared using GSVA and GSEA. Correlation studies were conducted to explore the relationship between the prognostic model, immune infiltration, immunotherapy response, and drug sensitivity. RESULTS: A cellular senescence-related signature comprising FOXM1, CDK1, CHEK1, and SERPINE1 was created and validated. High-risk patients showed significantly lower OS than low-risk patients. High-risk patients had carcinogenetic pathways activated, immunosuppressive cells infiltrated, and immunomodulatory genes overexpressed. They also showed higher sensitivity to EPZ004777_1237 and MK-2206_1053 and potential benefits from GSK-3 inhibitor IX, nortriptyline, lestaurtinib, and JNK-9L. CONCLUSIONS: This study constructed a cellular senescence-related signature that could be used to predict HCC patients' responses to and prognosis after TACE treatment, aiding in the development of personalized treatment plans.

Contextual bias by Forensic Document Examination trainees: An empirical study from China.

The impact of contextual bias has been repeatedly demonstrated across forensic domains; however, research on this topic in China is scarce. To examine the prevalence of contextual bias in pattern feature-comparison disciplines, we conducted an experiment involving 24 forensic document examination students. The aim was to determine whether knowledge of different contextual information influenced their forensic decision-making. Participants were divided into different context groups and tasked with examining whether questioned signatures with ambiguous features matched reference signatures. The results of independent-samples t-tests for their decision score data in the two context groups exhibited a statistically significant difference (p < 0.05, Cohen's d > 0.8). Moreover, the submitted forensic reports by participants disclosed a biased evaluation of handwriting features. These findings show how contextual information can bias forensic decision-making in handwriting examination. Context management with complementary strategies such as case triage, cognitive training and decision-making transparency must be implemented to minimize bias in handwriting examination.

Recent Advances in 3D Printing of Smart Scaffolds for Bone Tissue Engineering and Regeneration.

The repair and functional reconstruction of bone defects resulting from severe trauma, surgical resection, degenerative disease, and congenital malformation pose significant clinical challenges. Bone tissue engineering (BTE) holds immense potential in treating these severe bone defects, without incurring prevalent complications associated with conventional autologous or allogeneic bone grafts. 3D printing technology enables control over architectural structures at multiple length scales and has been extensively employed to process biomimetic scaffolds for BTE. In contrast to inert and functional bone grafts, next-generation smart scaffolds possess a remarkable ability to mimic the dynamic nature of native extracellular matrix (ECM), thereby facilitating bone repair and regeneration. Additionally, they can generate tailored and controllable therapeutic effects, such as antibacterial or antitumor properties, in response to exogenous and/or endogenous stimuli. This review provides a comprehensive assessment of the progress of 3D-printed smart scaffolds for BTE applications. It begins with an introduction to bone physiology, followed by an overview of 3D printing technologies utilized for smart scaffolds. Notable advances in various stimuli-responsive strategies, therapeutic efficacy, and applications of 3D-printed smart scaffolds are discussed. Finally, the review highlights the existing challenges in the development and clinical implementation of smart scaffolds, as well as emerging technologies in this field.

Social determinants of inflammatory markers linking depression and type 2 diabetes among women: A scoping review.

OBJECTIVE: Inflammation is implicated in the pathophysiology of depression and type 2 diabetes (T2D) and is linked to social determinants of health (SDoH) associated with socioeconomic disadvantage. The objective of this review is to identify and map the range of SDoHs associated with inflammation in depression, T2D, or their co-occurrence among women. METHODS: PubMed, CINAHL, PsychINFO, and Web of Science were searched March-July 2023 to identify studies where 1) an SDoH was a predictor or independent variable, 2) depression or T2D was a clinical focus, 3) inflammatory markers were collected, and 4) analysis was specific to women. We used the National Institute on Minority Health and Health Disparities research framework to guide searching SDoHs, organize findings, and identify gaps. RESULTS: Of the 1135 studies retrieved, 46 met criteria. Within the reviewed studies, the most used inflammatory measures were C-reactive protein, interleukin-6, and tumor necrosis factor-α, and the most studied SDoHs were early life stress and socioeconomic status. Individual and interpersonal-level variables comprised the bulk of SDoHs in the included studies, while few to no studies examined built environment (n = 6) or health system level (n = 0) factors. Disadvantageous SDoHs were associated with higher levels of inflammation across the included studies. CONCLUSION: The scope and intersection of depression and T2D represent a syndemic that contributes to and results from socioeconomic inequities and disproportionately affects women. Simultaneous inclusion of social and inflammatory measures, particularly understudied SDoHs, is needed to clarify potent targets aimed at advancing health and equity.

Anti-tumor efficacy of HRS-4642 and its potential combination with proteasome inhibition in KRAS G12D-mutant cancer.

KRAS G12D is the most frequently mutated oncogenic KRAS subtype in solid tumors and remains undruggable in clinical settings. Here, we developed a high affinity, selective, long-acting, and non-covalent KRAS G12D inhibitor, HRS-4642, with an affinity constant of 0.083 nM. HRS-4642 demonstrated robust efficacy against KRAS G12D-mutant cancers both in vitro and in vivo. Importantly, in a phase 1 clinical trial, HRS-4642 exhibited promising anti-tumor activity in the escalating dosing cohorts. Furthermore, the sensitization and resistance spectrum for HRS-4642 was deciphered through genome-wide CRISPR-Cas9 screening, which unveiled proteasome as a sensitization target. We further observed that the proteasome inhibitor, carfilzomib, improved the anti-tumor efficacy of HRS-4642. Additionally, HRS-4642, either as a single agent or in combination with carfilzomib, reshaped the tumor microenvironment toward an immune-permissive one. In summary, this study provides potential therapies for patients with KRAS G12D-mutant cancers, for whom effective treatments are currently lacking.