An Oxidative Enzyme Boosting Mechanical and Optical Performance of Densified Wood Films.

Nature has evolved elegant ways to alter the wood cell wall structure through carbohydrate-active enzymes, offering environmentally friendly solutions to tailor the microstructure of wood for high-performance materials. In this work, the cell wall structure of delignified wood is modified under mild reaction conditions using an oxidative enzyme, lytic polysaccharide monooxygenase (LPMO). LPMO oxidation results in nanofibrillation of cellulose microfibril bundles inside the wood cell wall, allowing densification of delignified wood under ambient conditions and low pressure into transparent anisotropic films. The enzymatic nanofibrillation facilitates microfibril fusion and enhances the adhesion between the adjacent wood fiber cells during densification process, thereby significantly improving the mechanical performance of the films in both longitudinal and transverse directions. These results improve the understanding of LPMO-induced microstructural changes in wood and offer an environmentally friendly alternative for harsh chemical treatments and energy-intensive densification processes thus representing a significant advance in sustainable production of high-performance wood-derived materials.

Lupus nephritis or not? A simple and clinically friendly machine learning pipeline to help diagnosis of lupus nephritis.

OBJECTIVE: Diagnosis of lupus nephritis (LN) is a complex process, which usually requires renal biopsy. We aim to establish a machine learning pipeline to help diagnosis of LN. METHODS: A cohort of 681 systemic lupus erythematosus (SLE) patients without LN and 786 SLE patients with LN was established, and a total of 95 clinical, laboratory data and 17 meteorological indicators were collected. After tenfold cross-validation, the patients were divided into training set and test set. The features selected by collective feature selection method of mutual information (MI) and multisurf were used to construct the models of logistic regression, decision tree, random forest, naive Bayes, support vector machine (SVM), light gradient boosting (LGB), extreme gradient boosting (XGB), and artificial neural network (ANN), the models were compared and verified in post-analysis. RESULTS: Collective feature selection method screens out antistreptolysin (ASO), retinol binding protein (RBP), lupus anticoagulant 1 (LA1), LA2, proteinuria and other features, and the hyperparameter optimized XGB (ROC: AUC = 0.995; PRC: AUC = 1.000, APS = 1.000; balance accuracy: 0.990) has the best performance, followed by LGB (ROC: AUC = 0.992; PRC: AUC = 0.997, APS = 0.977; balance accuracy: 0.957). The worst performance is naive Bayes model (ROC: AUC = 0.799; PRC: AUC = 0.822, APS = 0.823; balance accuracy: 0.693). In the composite feature importance bar plots, ASO, RF, Up/Ucr, and other features play important roles in LN. CONCLUSION: We developed and validated a new and simple machine learning pathway for diagnosis of LN, especially the XGB model based on ASO, LA1, LA2, proteinuria, and other features screened out by collective feature selection.

SOX2 Promotes Radioresistance in Non-small Cell Lung Cancer by Regulating Tumor Cells Dedifferentiation.

Background: Radiation therapy plays an important role in the treatment of patients with non-small cell lung cancer (NSCLC). However, the radiocurability is greatly limited because of radioresistance which leads to treatment failure, tumor recurrence, and metastasis. Cancer stem cell (CSC) has been identified as the main factor that contributes to radiation resistance. SOX2, one of the transcription factors specifically expressed in CSC, is involved in tumorigenesis, progression, and maintenance of cell stemness. But the association between SOX2 and NSCLC radioresistance is not clear now. Methods: We constructed the radiotherapy-resistant cell line of NSCLC by multiple radiotherapy treatments. Colony formation assay, western blot, and immunofluorescence were performed to detect the radiosensitivity of cells. Western blot, qRT-PCR, and sphere formation assay were used to detect CSC characteristics of cells. Wound healing assay and Transwell assay were used to determine cell migration motility. The SOX2-upregulated model and SOX2-downregulated model was constructed by lentivirus transduction. Finally, the expression and clinical relevance of SOX2 in NSCLC were investigated by bioinformatics analysis based on TCGA and GEO datasets. Results: The expression of SOX2 was increased in radioresistant cells and a trend of dedifferentiation were observed. The results of wound healing assay and Transwell assay showed that SOX2 overexpression significantly promote the migration and invasion of NSCLC cells. Mechanistically, overexpression of SOX2 enhanced radioresistance and DNA damage repair capability of parental cells, while down-regulation of SOX2 led to decreased radioresistance and DNA repair ability in radioresistant cells, all of which were related to cells dedifferentiation regulated by SOX2. In addition, bioinformatics analysis show that high expression of SOX2 was strongly associated with the progression and poor prognosis of patients with NSCLC. Conclusions: Our study revealed that SOX2 regulates radiotherapy resistance in NSCLC via promoting cell dedifferentiation. Therefore, SOX2 may be a promising therapeutic target for overcoming radioresistance in NSCLC, providing a new perspective to improve the curative effect.

Annexin A1 promotes the progression of bladder cancer via regulating EGFR signaling pathway.

BACKGROUND: Bladder cancer (BLCA) is one of the most common malignancies worldwide. One of the main reasons for the unsatisfactory management of BLCA is the complex molecular biological mechanism. Annexin A1 (ANXA1), a Ca2+-regulated phospholipid-binding protein, has been demonstrated to be implicated in the progression and prognosis of many cancers. However, the expression pattern, biological function and mechanism of ANXA1 in BLCA remain unclear. METHODS: The clinical relevance of ANXA1 in BLCA was investigated by bioinformatics analysis based on TCGA and GEO datasets. Immunohistochemical (IHC) analysis was performed to detect the expression of ANXA1 in BLCA tissues, and the relationships between ANXA1 and clinical parameters were analyzed. In vitro and in vivo experiments were conducted to study the biological functions of ANXA1 in BLCA. Finally, the potential mechanism of ANXA1 in BLCA was explored by bioinformatics analysis and verified by in vitro and in vivo experiments. RESULTS: Bioinformatics and IHC analyses indicated that a high expression level of ANXA1 was strongly associated with the progression and poor prognosis of patients with BLCA. Functional studies demonstrated that ANXA1 silencing inhibited the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of BLCA cells in vitro, and suppressed the growth of xenografted bladder tumors in vivo. Mechanistically, loss of ANXA1 decreased the expression and phosphorylation level of EGFR and the activation of downstream signaling pathways. In addition, knockdown of ANXA1 accelerated ubiquitination and degradation of P-EGFR to downregulate the activation of EGFR signaling. CONCLUSIONS: These findings indicate that ANXA1 is a reliable clinical predictor for the prognosis of BLCA and promotes proliferation and migration by activating EGFR signaling in BLCA. Therefore, ANXA1 may be a promising biomarker for the prognosis of patients with BLCA, thus shedding light on precise and personalized therapy for BLCA in the future.

Enhanced home-field advantage in deep soil organic carbon decomposition: Insights from soil transplantation in subtropical forests.

Climate change affects microbial community physiological strategies and thus regulates global soil organic carbon (SOC) decomposition. However, SOC decomposition by microorganisms, depending on home-field advantage (HFA, indicating a faster decomposition rate in 'Home' than 'Away' conditions) or environmental advantage (EA, indicating a faster decomposition rate in warmer-wetter environments than in colder-drier environments) remains unknown. Here, a soil transplantation experiment was conducted between warmer-wetter and colder-drier evergreen broadleaved forests in subtropical China. Specifically, soil samples were collected along a 60 cm soil profile, including 0-15, 15-30, 30-45, and 45-60 cm layers after one year of transplantation. SOC fractions, soil chemical properties, and microbial communities were evaluated to assess where there was an HFA of EA in SOC decomposition, along with an exploration of internal linkages. Significant HFAs were observed, particularly in the deep soils (30-60 cm) (P < 0.05), despite the lack of a significant EA along a soil profile, which was attributed to environmental changes affecting soil fungal communities and constraining SOC decomposition in 'Away' conditions. The soils transplanted from warmer-wetter to colder-drier environments changed the proportions of Mortiereltomycota or Basidiomycota fungal taxa in deep soils. Furthermore, the shift from colder-drier to warmer-wetter environments decreased fungal α-diversity and the proportion of fungal necromass carbon, ultimately inhibiting SOC decomposition in 'Away' conditions. However, neither HFAs nor EAs were significantly present in the topsoil (0-30 cm), possibly due to the broader adaptability of bacterial communities in these layers. These results suggest that the HFA of SOC decomposition in deep soils may mostly depend on the plasticity of fungal communities. Moreover, these results highlight the key roles of microbial communities in the SOC decomposition of subtropical forests, especially in deep soils that are easily ignored.

Mixed-linkage (1,3;1,4)-ß-d-glucans as rehydration media for improved redispersion of dried cellulose nanofibrils.

Improving the redispersion and recycling of dried cellulose nanofibrils (CNFs) without compromising their nanoscopic dimensions and inherent mechanical properties are essential for their large-scale applications. Herein, mixed-linkage (1,3;1,4)-ß-d-glucan (MLG) was studied as a rehydration medium for the redispersion and recycling of dried CNFs, benefiting from the intrinsic affinity of MLG to both cellulose and water molecules as inspired from plant cell wall. MLG from barley with a lower molar ratio of cellotriosyl to cellotetraosyl units was found homogeneously coated on CNFs, facilitating rehydration of the network of individualized CNFs. The addition of barley MLG did not impair the mechanical properties of the CNF/MLG composites as compared to neat CNFs nanopaper. With the addition of 10 wt% barley MLG, dry CNF/MLG composite film was successfully redispersed in water and recycled with well-maintained mechanical properties, while lichenan from Icelandic moss, cationic starch, and xyloglucan could not help the redispersion of dried CNFs.

Wood xerogel for fabrication of high-performance transparent wood.

Optically transparent wood has been fabricated by structure-retaining delignification of wood and subsequent infiltration of thermo- or photocurable polymer resins but still limited by the intrinsic low mesopore volume of the delignified wood. Here we report a facile approach to fabricate strong transparent wood composites using the wood xerogel which allows solvent-free infiltration of resin monomers into the wood cell wall under ambient conditions. The wood xerogel with high specific surface area (260 m2 g-1) and high mesopore volume (0.37 cm3 g-1) is prepared by evaporative drying of delignified wood comprising fibrillated cell walls at ambient pressure. The mesoporous wood xerogel is compressible in the transverse direction and provides precise control of the microstructure, wood volume fraction, and mechanical properties for the transparent wood composites without compromising the optical transmittance. Transparent wood composites of large size and high wood volume fraction (50%) are successfully prepared, demonstrating potential scalability of the method.

CD1B is a Potential Prognostic Biomarker Associated with Tumor Mutation Burden and Promotes Antitumor Immunity in Lung Adenocarcinoma.

Purpose: Tumor mutation burden (TMB) and tumor-infiltrating lymphocytes (TILs) have been well recognized as molecular determinants of immunotherapy responsiveness. In this study, we aimed to construct a TMB prognostic model and explore biomarkers that have predictive potential for prognosis and therapeutic effect in lung adenocarcinoma (LUAD). Patients and Methods: The TCGA, GEO and Immport databases were used to analyze the mutation profiles and immune infiltration of LUAD. TMB scores were calculated and differential analysis was conducted to identify TMB-related genes. Then, Cox regression model and survival analysis were applied to identify the prognostic genes and construct a TMB prognostic model. The expression and prognostic value of CD1B were further verified by immunohistochemistry (IHC) in 92 patient tissue samples. GSEA was performed to analyze the signaling pathways associated with CD1B expression. Results: High-TMB samples exhibited higher infiltration of CD8+ T cells, CD4+ memory T cells, and M1 macrophages. A total of 397 TMB-related differentially expressed genes were identified, of which 47 were immune-related genes. Cox regression analyses determined 3 hub TMB-related immune genes (CD1B, SCGB3A1, and VEGFD) with prognostic effects, and a TMB prognostic model was constructed. The model demonstrated robust predictive ability in both the training (TCGA) and testing (GEO) datasets. Notably, CD1B was identified as an independent prognostic factor. IHC of clinical samples showed that low expression of CD1B was related to poor overall survival and advanced pathological stages. In addition, there was a strong positive correlation between CD1B and most immune checkpoint molecules, including PD-L1. CD1B expression was associated with immune cell infiltration and immune activation in LUAD. Conclusion: Our study constructed a TMB prognostic model that effectively predicted the prognosis of LUAD patients. CD1B expression is correlated with better prognosis and promotes antitumor immunity in LUAD, which may serve as a potential prognostic biomarker and immune-related therapeutic target for LUAD.

Strong Foam-like Composites from Highly Mesoporous Wood and Metal-Organic Frameworks for Efficient CO2 Capture.

Mechanical stability and multicycle durability are essential for emerging solid sorbents to maintain an efficient CO2 adsorption capacity and reduce cost. In this work, a strong foam-like composite is developed as a CO2 sorbent by the in situ growth of thermally stable and microporous metal-organic frameworks (MOFs) in a mesoporous cellulose template derived from balsa wood, which is delignified by using sodium chlorite and further functionalized by 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidation. The surface carboxyl groups in the TEMPO-oxidized wood template (TO-wood) facilitate the coordination of the cellulose network with multivalent metal ions and thus enable the nucleation and in situ growth of MOFs including copper benzene-1,3,5-tricarboxylate [Cu3(BTC)2], zinc 2-methylimidazolate, and aluminum benzene-1,3,5-tricarboxylate. The TO-wood/Cu3(BTC)2 composite shows a high specific surface area of 471 m2 g-1 and a high CO2 adsorption capacity of 1.46 mmol g-1 at 25 °C and atmospheric pressure. It also demonstrates high durability during the temperature swing cyclic CO2 adsorption/desorption test. In addition, the TO-wood/Cu3(BTC)2 composite is lightweight but exceptionally strong with a specific elastic modulus of 3034 kN m kg-1 and a specific yield strength of 68 kN m kg-1 under the compression test. The strong and durable TO-wood/MOF composites can potentially be used as a solid sorbent for CO2 capture, and their application can possibly be extended to environmental remediation, gas separation and purification, insulation, and catalysis.

Surface Charges Control the Structure and Properties of Layered Nanocomposite of Cellulose Nanofibrils and Clay Platelets.

The interfacial bonding and structure at the nanoscale in the polymer-clay nanocomposites are essential for obtaining desirable material and structure properties. Layered nanocomposite films of cellulose nanofibrils (CNFs)/montmorillonite (MTM) were prepared from the water suspensions of either CNFs bearing quaternary ammonium cations (Q-CNF) or CNFs bearing carboxylate groups (TO-CNF) with MTM nanoplatelets carrying net surface negative charges by using vacuum filtration followed by compressive drying. The effect of the ionic interaction between cationic or anionic charged CNFs and MTM nanoplatelets on the structure, mechanical properties, and flame retardant performance of the TO-CNF/MTM and Q-CNF/MTM nanocomposite films were studied and compared. The MTM nanoplatelets were well dispersed in the network of TO-CNFs in the form of nanoscale tactoids with the MTM content in the range of 5-70 wt %, while an intercalated structure was observed in the Q-CNF/MTM nanocomposites. The resulting TO-CNF/MTM nanocomposite films had a better flame retardant performance as compared to the Q-CNF/MTM films with the same MTM content. In addition, the effective modulus of MTM for the TO-CNF/MTM nanocomposites was as high as 129.9 GPa, 3.5 times higher than that for Q-CNF/MTM (37.1 GPa). On the other hand, the Q-CNF/MTM nanocomposites showed a synergistic enhancement in the modulus and tensile strength together with strain-to-failure and demonstrated a much better toughness as compared to the TO-CNF/MTM nanocomposites.

Effect of antitumor therapy on cancer patients infected by SARS-CoV-2: A systematic review and meta-analysis.

BACKGROUND: Cancer patients are at a high risk of being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and are more likely to develop severe illness and have higher mortality once infected. In the COVID-19 pandemic, it is urgent to understand the effects of antitumor therapy on the prognosis of patients with COVID-19. METHODS: A systematic literature search was conducted in PubMed, Cochrane Library, Embase, MedRxiv, and Chinese National Knowledge Infrastructure (CNKI) until 21 June 2020. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were evaluated using a random effects model to analyze the effects of antitumor therapies on COVID-19 patients. RESULTS: For cancer patients with COVID-19, the death events related to antitumor treatment were higher than those with no antitumor treatment (OR = 1.55; 95% CI 1.07-2.25; p = 0.021). Compared with patients in the survival group, the non-survival group showed no significant differences in patients who received antitumor therapy. Compared with patients in the non-severe group, the severe group was more likely to receive antitumor therapy (OR = 1.50; 95% CI 1.02-2.19; p = 0.037) and there was a significant difference. The incidence of severe events was higher in the subgroup of chemotherapy (OR = 1.73; 95% CI 1.09-2.73). CONCLUSION: The synthesized evidence suggests that cancer patients with COVID-19 who received antitumor treatment shortly before symptom onset are more likely to experience severe symptoms and have high mortality. Receiving chemotherapy is an unfavorable factor for the prognosis of cancer patients with COVID-19.

High strength and low swelling composite hydrogels from gelatin and delignified wood.

A delignified wood template with hydrophilic characteristics and high porosity was obtained by removal of lignin. Gelatin was infiltrated into the delignified wood and further crosslinked with a natural crosslinker genipin to form hydrogels. The composite hydrogels showed high mechanical strength under compression and low swelling in physiological condition. The effect of genipin concentrations (1, 50 and 100 mM) on structure and properties of the composite hydrogels were studied. A porous honeycomb structure with tunable pore size and porosity was observed in the freeze-dried composite hydrogels. High elastic modulus of 11.82 ± 1.51 MPa and high compressive yield stress of 689.3 ± 34.9 kPa were achieved for the composite hydrogel with a water content as high as 81%. The equilibrium water uptake of the freeze-dried hydrogel in phosphate buffered saline at 37 °C was as low as 407.5%. These enables the delignified wood structure an excellent template in composite hydrogel preparation by using infiltration and in-situ synthesis, particularly when high mechanical strength and stiffness are desired.

Self-Densification of Highly Mesoporous Wood Structure into a Strong and Transparent Film.

In the native wood cell wall, cellulose microfibrils are highly aligned and organized in the secondary cell wall. A new preparation strategy is developed to achieve individualization of cellulose microfibrils within the wood cell wall structure without introducing mechanical disintegration. The resulting mesoporous wood structure has a high specific surface area of 197 m2 g-1 when prepared by freeze-drying using liquid nitrogen, and 249 m2 g-1 by supercritical drying. These values are 5 to 7 times higher than conventional delignified wood (36 m2 g-1 ) dried by supercritical drying. Such highly mesoporous structure with individualized cellulose microfibrils maintaining their natural alignment and organization can be processed into aerogels with high porosity and high compressive strength. In addition, a strong film with a tensile strength of 449.1 ± 21.8 MPa and a Young's modulus of 51.1 ± 5.2 GPa along the fiber direction is obtained simply by air drying owing to the self-densification of cellulose microfibrils driven by the elastocapillary forces upon water evaporation. The self-densified film also shows high optical transmittance (80%) and high optical haze (70%) with interesting biaxial light scattering behavior owing to the natural alignment of cellulose microfibrils.

Crystal structures and kinetic properties of enoyl-acyl carrier protein reductase I from Candidatus Liberibacter asiaticus.

Huanglongbing (HLB) is a destructive citrus disease. The leading cause of HLB is Candidatus Liberibacter asiaticus. Fatty acid biosynthesis is essential for bacterial viability and has been validated as a target for the discovery of novel antibacterial agents. Enoyl-acyl carrier protein reductase (also called ENR or FabI and a product of the fabI gene) is an enzyme required in a critical step of bacterial fatty acid biosynthesis and has attracted attention as a target of novel antimicrobial agents. We determined the crystal structures of FabI from Ca. L. asiaticus in its apoform as well as in complex with b-nicotinamide adenine dinucleotide (NAD) at 1.7 and 2.7 Å resolution, respectively, to facilitate the design and screening of small molecule inhibitors of FabI. The monomeric ClFabI is highly similar to other known FabI structures as expected; however, unlike the typical tetramer, ClFabI exists as a hexamer in crystal, whereas as dimer in solution, on the other hand, the substrate binding loop which always disordered in apoform FabI structures is ordered in apo-ClFabI. Interestingly, the structure of ClFabI undergoes remarkable conformational change in the substrate-binding loop in the presence of NAD. We conclude that the signature sequence motif of FabI can be considered as Gly-(Xaa)5-Ser-(Xaa)n-Val-Tyr-(Xaa)6-Lys-(Xaa)n-Thr instead of Tyr-(Xaa)6-Lys. We have further identified isoniazid as a competitive inhibitor with NADH.