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Yunfeng Han,1 Long Xi,1,2 Fang Leng,3 Chenjie Xu,3 Ying Zheng1 1State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, 999078, People’s Republic of China; 2School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China; 3Department of Biomedical Engineering, City University of Hong Kong, Hong Kong SAR, People’s Republic of ChinaCorrespondence: Ying Zheng; Chenjie Xu, Tel +853 88224687 ; +852 34424169, Fax +853 28841358, Email yzheng@umac.mo; chenjie.xu@cityu.edu.hkPurpose: Psoriasis is a chronic and recurrent inflammatory dermatitis characterized by T cell imbalance and abnormal keratinocyte proliferation. MicroRNAs (miRNAs) hold promise as therapeutic agents for this disease; however, their clinical application is hindered by poor stability and limited skin penetration. This study demonstrates the utilization of Framework Nucleic Acid (FNA) for the topical delivery of miRNAs in psoriasis treatment.Methods: By utilizing miRNA-125b as the model drug, FNA-miR-125b was synthesized via self-assembly. The successful synthesis and stability of FNA-miR-125b in bovine fetal serum (FBS) were verified through gel electrophoresis. Subsequently, flow cytometry was employed to investigate the cell internalization on HaCaT cells, while qPCR determined the effects of FNA-miR-125b on cellular functions. Additionally, the skin penetration ability of FNA-miR-125b was assessed. Finally, a topical administration study involving FNA-miR-125b cream on imiquimod (IMQ)-induced psoriasis mice was conducted to evaluate its therapeutic efficacy.Results: The FNA-miR-125b exhibited excellent stability, efficient cellular internalization, and potent inhibition of keratinocyte proliferation. In the psoriasis mouse model, FNA-miR-125b effectively penetrated the skin tissue, resulting in reduced epidermal thickness and PASI score, as well as decreased levels of inflammatory cytokines. Keywords: psoriasis, topical delivery, miRNA-125b, framework nucleic acid, FNA

Zhifen Qiao,1,* Shiyi Huang,1,* Fang Leng,1,2 Yu Bei,2 Yingzhi Chen,2 Minjie Chen,2 Yunfeng Hu,3 Yadong Huang,1,2 Qi Xiang1,2 1Institute of Biomedicine and Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou, 510632, People’s Republic of China; 2Biopharmaceutical R&D Center of Jinan University, Guangzhou, 510632, People’s Republic of China; 3The First Affiliated Hospital of Jinan University, Department of Dermatology, Guangzhou, 510632, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qi XiangInstitute of Biomedicine and Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou, 510632, People’s Republic of ChinaTel +86-020-8556-3234Email txiangqi@jnu.edu.cnBackground: Sensitive skin (SS) is easily irritated by various environmental stimuli, and epidemiological surveys surprisingly find that self-perceived SS is widespread worldwide.Objective: To investigate whether SS is linked to changes in the skin bacterial population using 16S rRNA sequencing and bioinformatic analysis.Patients and Methods: According to both the Huaxi SS Questionnaire and Lactic Acid Stimulation Test, 60 female volunteers in Guangzhou were classified into normal skin (NS) and SS groups. Skin barrier parameters were assessed by the CK skin tester. The DNA of the bacterial flora on the facial skin surface was extracted and was subjected to 16S rRNA sequencing.Results: The skin hydration was significantly lower in the SS group compared to the NS group (P =0.032). Based on 16S rRNA sequencing and bioinformatic analysis, the number of operational taxonomic units (OTUs) significantly decreased in the SS group (P =0.0235, SS vs NS). The relative abundance of Neisseriaceae in SS group decreased significantly (P < 0.05, SS vs NS), while that of Neisseria (within the Neisseriaceae family) increased significantly (P < 0.05, SS vs NS).Conclusion: SS is accompanied by a decrease in species diversity and richness, which may be relevant to the weakening of the microbial barrier (due to the increase of Neisseria or the decrease of Neisseriaceae). Thus, corresponding treatment for Neisseriaceae may be a new idea in the treatment of SS.Keywords: sensitive skin, 16S rRNA sequencing, bacterial, skin microbiome, skin barrier

RPKI Relying party needs to synchronizing data from repository periodically to verify information. In general, Rsync and RRDP are the two common means to complete data synchronization, however, each of them has related problems. In order to solve these problems, through analyzingthe way for synchronizing data from repository by the relying party, a mathematical model was established. Furthermore, based on the current problems faced by the two synchronization means, an improved RPKI data synchronization scheme was proposed. The advantages and disadvantages of the improved scheme were analyzed in detail, as well as the applicable scenarios. The improved scheme could provide a reference for optimizing the deployment and application of RPKI.

Rice husk ash is a kind of volcanic ash material with high silicon. This also provides a feasibility for rice husk ash as cement-based auxiliary cementing material. China is rich in rice husk resources, and the rice husk ash is stacked. Using rice husk ash (RHA) instead of traditional cementitious materials can effectively solve the environmental pollution caused by the accumulation of rice husk ash. Domestic and international scholar have added rice husk ash as mineral admixture to concrete, but the utilization rate is very low. In order to increase the added value of rice husk ash, the high silicon property of rice husk ash was used to solidify soil. The application range of solidified soil is wide, the requirements for materials are not high, and the functions are different, which can realize the extensive use of rice husk ash. This paper summarizes the literature on comprehensive utilization of rice husk ash at home and abroad, systematically expounds the physicochemical properties and production process of rice husk ash, introduces the application of rice husk ash in solidified soil, and points out the unsolved problems in this field, which provides a direction for the further development.

High non-starch polysaccharide (NSP) feedstuff in pig diet decreased the nutrient digestibility. It led to more digestion residual flowing into the hindgut and resulted in more odor emission. The supplementation of NSPase in high NSP diets was an effective approach to overcome the problem. This study applied fecal microbial enzyme activity and odorous substances as parameters to compare the odor reduction effects resulting from different NSPase products. The experimental diets including: (1) XY11 (from Taiwan Sugar Corporation) and (2) Commercial NSPase (Rovabio Advance). The experimental diets were fed for 8 weeks to growing pigs. The XY11 feeding resulted in a lower Salmonella count in the feces, it also showed higher average daily gain and growth uniformity than the commercial NSPase group. The fecal enzyme activity and the concentration of odorous compounds showed no significant difference between two feeding groups. It suggested that XY11 supplementation had a similar effect on odor reduction to commercial NSPase and showed benefit to growth performance. [ABSTRACT FROM AUTHOR]

Crude protein is often provided in excess in swine diets to improve growth performance. However, high-protein diets resulted in excess excretion of nitrogenous waste. This study investigates the effects of increased dietary NSP and enzyme supplementation on the reduction of fecal odor emission. Test treatments including: (1) Control diet (11.0 % NSP); (2) High NSP: (NSP adjusted to 16.5 % by soybean hull); (3) NSPase: Diet 2 with NSPase; (3) NSPase + Pro: Diet 2 with NSPase and protease. The average daily grain and feed intake among all treatments showed no difference. Compared to the control diet, the concentrations of NH3-N, P-cresol, indole, and skatole in feces from pigs fed high NSP diet were decreased significantly. Fecal NH3-N and P-cresol concentrations in NSPase treatment group were significantly higher than the high NSP feeding group. However, all fecal odor compounds concentrations in NSPase + Pro feeding group were significantly higher than the high NSP feeding group. In conclusion, increasing the dietary NSP resulted in the reduction of fecal odor emission without sacrificing the growth performance. Enzyme supplementation in a high NSP diet might potentially increase the fecal odor emission. [ABSTRACT FROM AUTHOR]

This paper discusses the seismic analysis of concrete dams with consideration of material nonlinearity. Based on a consistent rate-dependent model and two thermodynamics-based models, two thermodynamics-based rate-dependent constitutive models were developed with consideration of the influence of the strain rate. They can describe the dynamic behavior of concrete and be applied to nonlinear seismic analysis of concrete dams taking into account the rate sensitivity of concrete. With the two models, a nonlinear analysis of the seismic response of the Koyna Gravity Dam and the Dagangshan Arch Dam was conducted. The results were compared with those of a linear elastic model and two rate-independent thermodynamics-based constitutive models, and the influences of constitutive models and strain rate on the seismic response of concrete dams were discussed. It can be concluded from the analysis that, during seismic response, the tensile stress is the control stress in the design and seismic safety evaluation of concrete dams. In different models, the plastic strain and plastic strain rate of concrete dams show a similar distribution. When the influence of the strain rate is considered, the maximum plastic strain and plastic strain rate decrease.

Abstract Background A high concentration of cisplatin (CDDP) induces apoptosis in many tumor cell lines. CDDP has been administered by infusion to avoid severe toxicity. Recently, it has been reported that changes in survivin expression or function may lead to tumor sensitization to chemical and physical agents. The aim of this study was to determine whether a dominant-negative mouse survivin mutant could enhance the anti-tumor activity of CDDP. Methods A plasmid encoding the phosphorylation-defective dominant-negative mouse survivin threonine 34→alanine mutant (survivin T34A) complexed to a DOTAP-chol liposome (Lip-mS) was administered with or without CDDP in Lewis Lung Carcinoma (LLC) cells and in mice bearing LLC tumors, and the effects on apoptosis, tumor growth and angiogenesis were assessed. Data were analyzed using one-way analysis of variance(ANOVA), and a value of P < 0.05 was considered to be statistically significant. Results LLC cells treated with a combination of Lip-mS and CDDP displayed increased apoptosis compared with those treated with Lip-mS or CDDP alone. In mice bearing LLC tumors and treated with intravenous injections of Lip-mS and/or CDDP, combination treatment significantly reduced the mean tumor volume compared with either treatment alone. Moreover, the antitumor effect of Lip-mS combined with CDDP was greater than their anticipated additive effects. Conclusion These data suggest that the dominant-negative survivin mutant, survivin T34A, sensitized LLC cells to chemotherapy of CDDP. The synergistic antitumor activity of the combination treatment may in part result from an increase in the apoptosis of tumor cells, inhibition of tumor angiogenesis and induction of a tumor-protective immune response.

Objective: To identify genetic variants associated with Stanford A thoracic aortic aneurysm and dissection (ATAAD) using whole-exome sequencing (WES) and analyze positive mutation rates among patients of different onset ages. Methods: WES was performed on 62 sporadic Chinese ATAAD patients (51-74 years old), and then grouped based on onset age together with 73 previously reported TAAD patients (19-50 years old): ≤35, 36-45, 46-55, and >55 years. The proportion of patients with pathogenic/likely pathogenic (P/LP) variants in TAAD causal genes was compared across groups. Results: The average onset age of the 62 patients was 57.66 years. Eight P/LP variants were identified (two novel, six previously described) in five known TAAD causal genes ( FBN1 , SMAD3 , TGFBR2 , TGFB2 , and MYLK ) in eight individuals. P/LP variant positive rates among patients across age groups were: 22.73% for ≤35 years, 32% for 36-45 years, 15.52% for 46-55 years, and 3.33% for >55 years. Significant differences ( p = 0.0077) were observed between 36-45 and >55 years group. Conclusions: ATAAD patients aged 36-45 years old at diagnosis had a higher chance of having a P/LP variant and patients >55 years old had the lowest P/LP diagnostic rate. Therefore, gene screening in ATAAD patients ≤55 years old is key to improved diagnostic rate.

Macrophage polarization facilitates the inflammatory response and intensified fibrosis in the silicosis microenvironment by a mechanism related to macrophage pyroptosis, although the upstream target remains poorly defined. Currently, there are few reports on the development of drugs that alleviate macrophage polarization by dampening pyroptosis. The present study aims to explore the mechanics of silica mediating macrophage polarization and to investigate whether quercetin (Que) can depolarize macrophages with this mechanism. Silica processing led to prominent M1 polarization of macrophages. Additionally, significant macrophage polarization could be detected in the lung tissue of mice with airway-perfused silica. Further investigation turned out that pronounced mitochondria damage, mtDNA cytoplasmic ectomy, and pyroptosis occurred in response to silica. Nevertheless, Que treatment could effectively attenuate silica-induced mitochondria damage and pyroptosis as demonstrated in vitro and in vivo. Further exploration presented Que could bind to TOM70 and restore silica-induced mitochondrial damage. More importantly, the M1 polarization of macrophage was depressed with the co-treatment of Que and silica, wherein the inflammatory response and pulmonary fibrosis were also mitigated without obvious damage to vital organs. In conclusion, these findings proved that silica leads to mitochondrial damage, thereby evoking pyroptosis and promoting macrophage M1 polarization. Que could bind to TOM70 and restore its function, suppressing mitochondrial damage and pyroptosis, and depolarizing macrophages to reduce fibrosis, which provides a promising strategy for silicosis treatment in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ultrasonic-mediated plasmid transformation is a promising microbial transformation strategy with broad application prospects that has attracted interest across various fields. Limited research exists on developing a quantitative model to understand the relationship between transformation efficiency and ultrasonic power. Within the ultrasonic range that did not damage plasmids, the maximum transformation efficiency reached at 4.84 × 10 5 CFU/μg DNA. A kinetic model based on changes in membrane permeability was utilized to determine the membrane permeability at different power levels. The results indicated a linear correlation between ultrasonic power, transformation efficiency, and membrane permeability within a specific range. A quantitative relationship model was established based on ultrasonic power and transformation efficiency in E. coli. Electron microscopy revealed that E. coli cells subjected to ultrasonic treatment exhibited pore formation and cellular expansion. Furthermore, the integrity of the bacterial membrane was compromised as ultrasonic power increased. Nine genes associated with the functional terms of cell membrane components and transmembrane transport were identified in E. coli DH5α. According to qRT-PCR results, genes with these functions (including cusC, uidC, tolQ, tolA, ompC, yaiY) play crucial roles in ultrasound-mediated transformation of E. coli DH5α. This study suggested that ultrasound-mediated transformation in E. coli DH5α is not a simple physical-chemical process but rather involves the regulation of responsive membrane-related genes. This research establishes the groundwork for future comprehensive investigations into the molecular mechanism of ultrasound-mediated transformation and provides insights for the application of ultrasound technology in genetic engineering and related fields., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Stenotrophomonas rhizophila JC1 and its extracellular polysaccharides (EPS) have been shown to effectively adsorb heavy metals in previous studies. The fermentation conditions of EPS by S. rhizophila JC1 were optimized using the Box-Behnken design (BBD). The composition, structural characteristics, and heavy metal adsorption capacity of EPS were systematically evaluated. The alleviation mechanism of Pb 2+ stress on alfalfa was investigated through EPS inoculation. The maximum EPS yield reached 0.313 %. EPS consisted of glucose, glucosamine, galactose, and mannose in a molar ratio of 12.20:1:22.29:1.68. EPS also contained four distinct polymers with molecular weights of 623,683.71 Da, 144,072.27 Da, 105,892.21 Da, and 51,094.79 Da. The adsorption processes conformed to the pseudo-second-order model and Langmuir isotherm model. High Pb 2+ concentrations significantly reduced germination percentage, germinative force, root length, fresh weight, and soluble protein, inhibited photosynthesis, exacerbated oxidative stress, and caused damage to the antioxidant system, thereby inhibiting seedling growth. EPS at low concentrations can promote alfalfa seed germination and mitigate Pb 2+ stress by reducing the aforementioned damage. This study highlights the potential of EPS in soil remediation and enhancing plant resistance to heavy metal stress., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Background: Chemotherapy for colorectal cancer (CRC) urgently needs low-toxicity and highly effective phytomedicine. Cepharanthine (Cep) shown to have multiple anti-tumor effects, including colorectal cancer, whose pivotal mechanisms are not fully understood. Herein, the present work aims to reveal the impact of Cep on the mitochondrial and anti-injury functions of CRC cells., Methods: The TOM70/20 expression was screened by bioinformatic databases. SW480 cells were utilized as the colorectal cancer cell model. The expression of TOM70/20 and the downstream molecules were measured by western blots (WB). The ferroptosis was analyzed using Transmission electron microscopy (TEM), C11-BODIPY, PGSK, and DCFH-DA probes, wherein the detection was performed by flow cytometry and laser confocal microscopy. The anti-cancer efficacy was conducted by CCK-8 and Annexin-V/PI assay. The rescue experiments were carried out using Fer-1 and TOM70 plasmid transfection., Results: Bioinformatic data identified TOM20 and TOM70 were highly expressed in colorectal cancer, which could be down-regulated by Cep. Further findings disclosed that Cep treatment destroyed the mitochondria and inactivated the NRF2 signaling pathway, an essential pathway for resistance to ferroptosis, thereby promoting reactive oxygen species (ROS) generation in CRC cells. As a result, prominent ferroptosis could be observed in CRC cells in response to Cep, which thereby led to the reduced cell viability of cancer cells. On the contrary, recovery of TOM70 dampened the Cep-elicited mitochondria damage, ferroptosis, and anti-cancer efficacy., Conclusion: In summary, Cep-mediated TOM inhibition inactivates the NRF2 signaling pathway, thereby triggering ferroptosis and achieving an anti-colorectal cancer effect. The current study provides an innovative chemotherapeutic approach for colorectal cancer with phytomedicine., (© 2024. The Author(s).)

Bolivia has abundant pebbles, while the supply of crushed stone is limited and unstable. Thus, the resource utilization of local pebble as a coarse aggregate and the guarantee of concrete durability are the key scientific issues in the Sucre Highway Project. In this paper, a comparative analysis was conducted of the performance of crushed stone concrete and pebble concrete. Additionally, the impact of fly ash on the water permeability resistance of concrete was investigated. The results indicate that the apparent density, bulk density, and void ratio of pebbles are lower than those of crushed stone, and the aggregate gradation of pebbles is dispersed. The type of aggregate is the primary factor influencing the splitting tensile strength of concrete, with the main failure modes of pebble concrete being slurry cracking, aggregate crushing, and interface debonding. While aggregate and fly ash have a minor effect on compressive strength, they significantly impact flexural tensile strength; however, all concretes meet the requirements for extra-heavy, very heavy, and heavy traffic load levels. In terms of impermeability, fly ash effectively mitigates the negative impact of aggregate type on the impermeability of concrete. These findings support the application of pebble concrete in the highway project.

In this study, we assessed the impact of varied water deficit irrigation frequencies (T1: 2.5 L/4 days; T2: 5 L/8 days; CK: 5 L/4 days) on Zitian Seedless grapes from veraison to post-ripening. Notably, total soluble solids increased during on-tree storage compared to at maturity, while total anthocyanin content decreased, particularly in CK (60.16%), T1 (62.35%), and less in T2 (50.54%). Glucose and fructose levels increased significantly in T1 and T2, more so in T2, but slightly declined in CK. Tartaric acid content increased by 41.42% in T2. Moreover, compared to regular irrigation, water deficit treatments enhanced phenolic metabolites and volatile compounds, including chlorogenic acid, various flavonoids, viniferin, hexanal, 2-nonenal, 2-hexen-1-ol, (E)-, 3-hydroxy-dodecanoic acid, and 1-hexanol, etc. Overall, the T2 treatment outperformed T1 and CK in maintaining grape quality. This study reveals that combining on-tree storage with water deficit irrigation not only improves grape quality but also water efficiency., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Knotted proteins are fascinating natural biomolecules whose backbones entangle themselves in a knot. Their particular knotted configurations provide them with a wide range of topological features. However, their folding/unfolding mechanisms, stability, and function are poorly understood. In the present work, native trapped ion mobility spectrometry-mass spectrometry (TIMS-MS) was used for characterizing structural features of two model knotted proteins: a Gordian 5 2 knot ubiquitin C-terminal hydrolase (UCH) and a Stevedore 6 1 knot (α-haloacid dehalogenase, DehI). Experimental results showed structural transitions of UCH and DehI as a function of solution composition (0-50% MeOH) and temperature ( T ∼20-95 °C). An increase in the protein charge states and collision cross sections (∼2750-8750 Å 2 and ∼3250-15,385 Å 2 for UCH and DehI, respectively) with the solution organic content (OC) and temperature suggested a three-step unfolding pathway with at least four structural transitions. Results also showed that the integrity of the UCH knot core was more resistant to thermal unfolding when compared to DehI; however, both knot cores can be disrupted with the increase in the solution OC. Additional enzymatic digestion experiments using carboxypeptidase Y combined with molecular dynamics simulations showed that the knot core was preserved between Glu20 and Glu188 and Arg89 and His304 residues for UCH and DehI, respectively, where disruption of the knot core led to structural collapse followed by unfolding events. This work highlights the potential of solution OC and temperature studies combined with native TIMS-MS for the comprehensive characterization of knotted proteins to gain a better understanding of their structural transitions.

Codonopsis pilosula , commonly known as Dangshen, is a valuable medicinal plant, but its slow growth and susceptibility to environmental stress pose challenges for its cultivation. In pursuit of sustainable agricultural practices to enhance the yield and quality of Dangshen, the present study isolated a bacterial strain exhibiting plant growth-promoting potential from the rhizosphere of C. pilosula . This strain was subsequently identified as Bacillus licheniformis YB06. Assessment of its plant growth-promoting attributes revealed the potential of B. licheniformis YB06 as a biofertilizer. Whole-genome sequencing of B. licheniformis YB06 revealed a genome size of 4,226,888 bp with a GC content of 46.22%, harboring 4325 predicted protein-coding sequences. Genomic analysis of B. licheniformis YB06 revealed a diverse array of genes linked to induced systemic resistance (ISR) and plant growth-promoting (PGP) traits, encompassing phytohormone production, nitrogen assimilation and reduction, siderophore biosynthesis, phosphate solubilization, biofilm formation, synthesis of PGP-related amino acids, and flagellar motility. Seed germination assays demonstrated the positive effects of B. licheniformis YB06 on the germination and growth of C. pilosula seedlings. Furthermore, we explored various fertilization regimes, particularly the B. licheniformis YB06-based biofertilizer, were investigated for their impact on the structure and diversity of the C. pilosula rhizosphere soil bacterial community. Our findings revealed that fertilization significantly impacted soil bacterial composition and diversity, with the combined application of B. licheniformis YB06-based biofertilizer and organic fertilizer exhibiting a particularly pronounced enhancement of rhizosphere bacterial community structure and diversity. This study represents the first report on the beneficial effects of B. licheniformis YB06 on both the growth of C. pilosula and the composition of its rhizosphere soil microbial community. These findings provide a theoretical foundation and practical guidance for the development of novel bio-organic compound fertilizers, thereby contributing to the sustainable cultivation of C. pilosula .

Background: Sepsis is a heterogeneous syndrome. This study aimed to identify new sepsis sub-phenotypes using plasma cortisol trajectory., Methods: This retrospective study included patients with sepsis admitted to the intensive care unit of Zhongshan Hospital Fudan University between March 2020 and July 2022. A group-based cortisol trajectory model was used to classify septic patients into different sub-phenotypes. The clinical characteristics, biomarkers, and outcomes were compared between sub-phenotypes., Results: A total of 258 patients with sepsis were included, of whom 186 were male. Patients were divided into two trajectory groups: the lower-cortisol group (n = 217) exhibited consistently low and slowly declining cortisol levels, while the higher-cortisol group (n = 41) showed relatively higher levels in comparison. The 28-day mortality (65.9% vs.16.1%, P < 0.001) and 90-day mortality (65.9% vs. 19.8%, P < 0.001) of the higher-cortisol group were significantly higher than the lower-cortisol group. Multivariable Cox regression analysis showed that the trajectory sub-phenotype (HR = 5.292; 95% CI 2.218-12.626; P < 0.001), APACHE II (HR = 1.109; 95% CI 1.030-1.193; P = 0.006), SOFA (HR = 1.161; 95% CI 1.045-1.291; P = 0.006), and IL-1β (HR = 1.001; 95% CI 1.000-1.002; P = 0.007) were independent risk factors for 28-day mortality. Besides, the trajectory sub-phenotype (HR = 4.571; 95% CI 1.980-10.551; P < 0.001), APACHE II (HR = 1.108; 95% CI 1.043-1.177; P = 0.001), SOFA (HR = 1.270; 95% CI 1.130-1.428; P < 0.001), and IL-1β (HR = 1.001; 95% CI 1.000-1.001; P = 0.015) were also independent risk factors for 90-day mortality., Conclusion: This study identified two novel cortisol trajectory sub-phenotypes in patients with sepsis. The trajectories were associated with mortality, providing new insights into sepsis classification., (© 2024. The Author(s).)

Despite the effectiveness of microbial-phytoremediation for remediating total petroleum hydrocarbons (TPH)-contaminated soil, the underlying mechanisms remain elusive. This study investigated the whole-genome and biological activity of Rhodococcus erythropolis KB1, revealing its plant growth promotion (PGP), TPH degradation, and stress resistance capabilities. Phytoremediation (using alfalfa) and plant-microbial remediation (using alfalfa and KB1) were employed to degrade TPH. The highest TPH degradation rate, reaching 95%, was observed with plant-microbial remediation. This is attributed to KB1's ability to promote alfalfa growth, induce the release of signaling molecules to activate plant antioxidant enzymes, actively recruit TPH-degrading bacteria (e.g., Sphingomonas, Pseudomonas, C1-B045), and increase soil nitrogen and phosphorus levels, thereby accelerating TPH degradation by both plants and microorganisms. This study demonstrates that R. erythropolis KB1 holds great potential for enhancing the remediation of TPH-contaminated soil through its multifaceted mechanisms, particularly in plant-microbial remediation strategies, providing valuable theoretical support for the application of this technology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Uveal melanoma is the most common intraocular malignant tumor in adults. For patients presenting with cataracts and glaucoma, it is recommended to assess whether an intraocular lesion is present as the primary cause. The present study describes the case of a 52-year-old man with primary intraocular malignant melanoma. The patient experienced painless vision loss in the right eye for 1 year, with recent onset of eye swelling and pain in the week prior to seeking medical attention. A slit-lamp examination revealed a shallow anterior chamber in the right eye, a visibly opaque lens and a faint reflection of the tumor surface in the vitreous humor. In addition, the intraocular pressure of this eye was >60 mmHg. Magnetic resonance imaging revealed a large tumor behind the lens measuring 16×18×14 mm. Pathological examination confirmed the diagnosis of malignant melanoma. No BRCA-associated protein-1 somatic mutation was detected, whereas germline mutations of MutL protein homolog 1, RAD54 like, and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 were identified. Extensive systemic examination excluded the possibility that the tumors originated from another part of the body. The present case report highlights the crucial role of slit-lamp examination in the detection of ocular tumors. It is advocated that for patients presenting with cataracts, attention should be paid to the possibility of intraocular tumors. Meticulous slit-lamp microscopy may reveal a reflection of the surface of a malignant melanoma, preventing misdiagnosis., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Wang et al.)

Daunorubicin and doxorubicin are among the most potent anti-cancer drugs and bind to DNA through intercalation. In this paper, we demonstrate that formaldehyde can efficiently and specifically conjugate daunorubicin and doxorubicin to GTP, resulting in the formation of daunorubicin-GTP-1 and doxorubicin-GTP-1 conjugates. The linkage occurs between the 2-NH 2 of guanine and the 3'-NH 2 of daunosamine. We characterized these daunorubicin/doxorubicin-GTP conjugates using various methods, including UV-Vis, fluorescence, CD, FT-IR, and mass spectrometry. Our results also indicate that these daunorubicin/doxorubicin-GTP conjugates bind to DNA via intercalation. Furthermore, we observed rapid accumulation of these conjugates in human cancer cells and observed cytotoxic effects in both doxorubicin-sensitive SK-OV-3 and doxorubicin-resistant NCI/ADR-RES cells, suggesting that these daunorubicin and doxorubicin derivatives can overcome doxorubicin resistance., (© 2024 Wiley-VCH GmbH.)

One of the fundamental techniques in genetic engineering is the creation of Escherichia coli competent cells using the CaCl 2 method. However, little is known about the mechanism of E. coli competence formation. We have previously found that the cspA gene may play an indispensable role in the preparation of E. coli DH5α competent cells through multiomics analysis. In the present study, the cellular localization, physicochemical properties, and function of the protein expressed by the cspA gene were analyzed. To investigate the role of the cspA gene in E. coli transformation, cspA-deficient mutant was constructed by red homologous recombination. The growth, transformation efficiency, and cell morphology of the cspA-deficient strain and E. coli were compared. It was found that there were no noticeable differences in growth and morphology between E. coli and the cspA-deficient strain cultured at 37°C, but the mutant exhibited increased transformation efficiencies compared to E. coli DH5α for plasmids pUC19, pET-32a, and p1304, with enhancements of 2.23, 2.24, and 3.46 times, respectively. It was proved that cspA gene is an important negative regulatory gene in the CaCl 2 preparation of competent cells., (© 2024 Wiley‐VCH GmbH.)

Single-cell RNA sequencing (scRNA-seq) has emerged as a valuable tool for studying cellular heterogeneity in various fields, particularly in virological research. By studying the viral and cellular transcriptomes, the dynamics of viral infection can be investigated at a single-cell resolution. However, limited studies have been conducted to investigate whether RNA transcripts from clinical samples contain substantial amounts of viral RNAs, and a specific computational framework for efficiently detecting viral reads based on scRNA-seq data has not been developed. Hence, we introduce DVsc, an open-source framework for precise quantitative analysis of viral infection from single-cell transcriptomics data. When applied to approximately 200 diverse clinical samples that were infected by more than 10 different viruses, DVsc demonstrated high accuracy in systematically detecting viral infection across a wide array of cell types. This innovative bioinformatics pipeline could be crucial for addressing the potential effects of surreptitiously invading viruses on certain illnesses, as well as for designing novel medicines to target viruses in specific host cell subsets and evaluating the efficacy of treatment. DVsc supports the FASTQ format as an input and is compatible with multiple single-cell sequencing platforms. Moreover, it could also be applied to sequences from bulk RNA sequencing data. DVsc is available at http://62.234.32.33:5000/DVsc., (© The Author(s) 2024. Published by Oxford University Press and Science Press on behalf of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China.)