A phase I trial of autologous RAK cell immunotherapy in metastatic renal cell carcinoma.

BACKGROUND: Treatment of metastatic renal cell carcinoma (mRCC) remains a challenge worldwide. Here, we introduced a phase I trial of autologous RAK cell therapy in patients with mRCC whose cancers progressed after prior systemic therapy. Although RAK cells have been used in clinic for many years, there has been no dose-escalation study to demonstrate its safety and efficacy. METHODS: We conducted a phase I trial with a 3 + 3 dose-escalation design to investigate the dose-related safety and efficacy of RAK cells in patients with mRCC whose cancers have failed to response to systemic therapy (ChiCTR1900021334). RESULTS: Autologous RAK cells, primarily composed of CD8+ T and NKT cells, were infused intravenously to patients at a dose of 5 × 109, 1 × 1010 or 1.5 × 1010 cells every 28 days per cycle. Our study demonstrated general safety of RAK cells in a total of 12 patients. Four patients (33.3%) showed tumor shrinkage, two of them achieved durable partial responses. Peripheral blood analysis showed a significant increase in absolute counts of CD3+ and CD8+ T cells after infusion, with a greater fold change observed in naive CD8+ T cells (CD8+CD45RA+). Higher peak values of IL-2 and IFN-γ were observed in responders after RAK infusion. CONCLUSION: This study suggests that autologous RAK cell immunotherapy is safe and has clinical activity in previously treated mRCC patients. The improvement in peripheral blood immune profiling after RAK cell infusion highlights its potential as a cancer treatment. Further investigation is necessary to understand its clinical utility.

First Report of Powdery Mildew on Cardamine violifolia in China.

Cardamine violifolia, also called Cardamine hupingshanensis, is an economically important medicinal plant renowned for accumulating selenium (Guo et al., 2022). Selenium is an essential trace element with anti-oxidant, anti-inflammatory, anti-cancer, and immune regulatory functions. In July 2023, an outbreak of powdery mildew was detected, infecting the leaves of numerous C. violifolia plants in Enshi (30°11'5.27''N; 109°48'48.45''E), Hubei Province, China. This disease caused severe damage to plant leaves and stems, starting as individual spots and merging into a large mold that covers the entire leaf. It affected nearly 25% all C. violifolia plants, resulting in significant yield loss, disruption of normal metabolism, and premature aging. The lower leaf blades and underside of the leaves were particularly vulnerable. The affected leaves were collected and subjected to morphological diagnostic analysis (Mori et al., 2000) (Fig. S1). The powdery mildew species aggressively spread throughout the leaves, pedicels, and pods, persisting until present and often covering the entire surface. The conidiophores were upright, cylindrical, composed of 3 to 4 cells, and measured 92.3 ± 12.9 × 9.2 ± 0.6 µm (n = 30). Conidial pedicels had 21.6 ± 3.4 µm (n = 50) long cylindrical podocytes. The monoconidia were columnar or barrel-columnar, 30.60-55.59 × 9.11-20.00 µm in size. Conidia lacked an obvious cellulose body. The bud tubes formed from the end of conidia, and papillary appressoria developed on the epiphytic mycelia. ITS region sequences were amplified using the specific powdery mildew universal primers ITS1 (5'-TCCGTAGGTGAACCTGCGG-3'), PM6 (5'-GYCRCYCTGTCGCGAG-3') for partial sequences of 18S and 28S ribosomal DNA genes (Takamatsu et al., 2001). The sequence was deposited in the GenBank under the accession number OR506156 and aligned with available sequences on NCBI, which were 99.2%(528/532) identical to the E. cruciferarum (MT309701, MF192845, and KY660929) sequences (Fig. S2). The ITS sequence from GenBank was used to conduct maximum likelihood phylogenetic analysis using MEGA 11.0. The analysis results showed both the strain and E. cruciferarum clustered on the same branch. To confirm Koch's postulates, pathogenicity testing was carried out using an illuminating incubator. Infected leaves were attached to healthy leaves of C. violifolia seedlings (n=8). All the plants were incubated under 25℃ and >80% relative humidity. After one month, all inoculated plants presented the same symptoms as those initially observed in the field. Morphological and molecular analysis confirmed the isolated fungi's identity as the same pathogen. Therefore, C. violifolia is a suitable host for E. cruciferarum in China. The growers must be informed of these findings to prevent serious economic losses caused by this pathogenic white powder and to prepare for proper management practices. To our knowledge, this is the first report of E. cruciferarum infecting C. violifolia in China.

Interleukin-17 and ischaemic stroke.

Interleukin-17 (IL-17) is a cytokine family that includes 6 members, IL-17A through IL-17F, most of them are reported to have pro-inflammatory role. Through binding to their receptors (IL-17Rs), IL-17 activates the intracellular signalling pathways to play an important role in autoimmune diseases, including rheumatoid arthritis (RA) and multiple sclerosis (MS). Ischaemic stroke is a complex pathophysiological process mainly caused by regional cerebral ischaemia. Inflammatory factors contribute to the physiological process of stroke that leads to poor prognosis. IL-17 plays a crucial role in promoting inflammatory response and inducing secondary injury in post-stroke. Though immune cells and inflammatory factors have been reported to be involved in the damage of stroke, the functions of IL-17 in this process need to be elucidated. This review focuses on the pathological modulation and the mechanism of IL-17 family in ischaemic stroke and seeking to provide new insights for future therapies.

Rapid Access to 2-Methylene Tetrahydrofurans and γ-Lactones: A Tandem Four-Step Process.

A one-pot tandem process involving hydrolysis, Knoevenagel condensation, Michael addition, and Conia-ene (HKMC) reactions has been developed for the rapid synthesis of indanone-fused 2-methylene tetrahydrofurans from the reaction of enynals and propynols. In this process, two rings and four bonds are generated with 100 % atom-economy and high step-efficiency. The resulting tetrahydrofurans were readily oxidized into α-methylene γ-lactones, which are one of the most important substructures in natural and bioactive compounds.

[A study of sub-healthy status of community residents and its relevant factors in Fuzhou City].

OBJECTIVE: To evaluate the sub-healthy status of community residents and its main relevant factors. METHODS: The proportional stratified random sampling was selected to take the sample of 5000 community residents from two communities in Fujian province. The sub-healthy status and its main influence factors were measured with the method of physical examination and questionnaire. RESULTS: The women, the oldest group (≥60 years old) and the divorce/widowed group were found to have the higher scores of sub-health status than others (P <0. 05). Multivariate analysis showed that female, age, education level and irregular eating were the main risk factors for the three dimensions of sub-health status. Divorced or widowed statue was unfavorable factors for physical and psychological sub-health status. Quit smoking was found to be significant risk factor for psychological and social sub-health status. Body mass index (BMI) was related to physical sub-health status, alone. While physical exercise was the main protective factor for sub-health status. CONCLUSION: Improving behavioral habits, maintaining stable family, maintaining normal BMI may be important to prevent sub-health status among community residents.

Synergistic Catalysis: Metal/Proton-Catalyzed Cyclization of Alkynones Toward Bicyclo[3.n.1]alkanones.

A highly efficient and practical synergistically metal/proton-catalyzed Conia-ene reaction for the synthesis of bicyclo[3.n.1]alkanones has been developed. This synergistic catalysis was successfully utilized in modifying natural compounds such as methyl dihydrojasmonate, α,ß-thujone, and 5α-cholestan-3-one. Furthermore, the bridged carbonyl group of bicyclo[3.2.1]alkanones could be easily attacked by nucleophiles to give the ring-opened cycloheptenone products or bicyclo[4.2.1]amide in excellent yields. These reactions provide rapid access to a diverse range of cyclic structures from simple starting materials or naturally occurring compounds.

Applications of deep learning models in precision prediction of survival rates for heart failure patients.

BACKGROUND: Heart failure poses a significant challenge in the global health domain, and accurate prediction of mortality is crucial for devising effective treatment plans. In this study, we employed a Seq2Seq model from deep learning, integrating 12 patient features. By finely modeling continuous medical records, we successfully enhanced the accuracy of mortality prediction. OBJECTIVE: The objective of this research was to leverage the Seq2Seq model in conjunction with patient features for precise mortality prediction in heart failure cases, surpassing the performance of traditional machine learning methods. METHODS: The study utilized a Seq2Seq model in deep learning, incorporating 12 patient features, to intricately model continuous medical records. The experimental design aimed to compare the performance of Seq2Seq with traditional machine learning methods in predicting mortality rates. RESULTS: The experimental results demonstrated that the Seq2Seq model outperformed conventional machine learning methods in terms of predictive accuracy. Feature importance analysis provided critical patient risk factors, offering robust support for formulating personalized treatment plans. CONCLUSIONS: This research sheds light on the significant applications of deep learning, specifically the Seq2Seq model, in enhancing the precision of mortality prediction in heart failure cases. The findings present a valuable direction for the application of deep learning in the medical field and provide crucial insights for future research and clinical practices.

Characterization of the complete chloroplast genome sequence of Bassia scoparia (L.) A. J. Scott 1978 (Amaranthaceae) and its phylogenetic analysis.

Bassia scoparia, an annual potherb belonging to the family Amaranthaceae, has been widely used in traditional Chinese and Japanese medicine for over 2000 years. Herein, we presented its complete chloroplast. The chloroplast genome sequence was 151,278 bp in length with a 36.6% content of GC. The genome showed the typical quadripartite structure, comprising a pair of inverted repeat (IR) regions (24,353 bp) separated by a large single-copy (LSC) region (84,067 bp) and a small single-copy (SSC) region (18,505 bp). This chloroplast genome harbored 133 predicted genes, including 88 protein-coding genes, 37 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. The phylogenetic analysis indicated that B. scoparia was closely related to B. littorea. This newly sequenced chloroplast genome not only enhances our understanding of the genome of Bassia but also provides valuable insights for the evolutionary study of the family Amaranthaceae.

The complete chloroplast genome sequence of Hydrocotyle vulgaris L. (Araliaceae).

Hydrocotyle vulgaris is a perennial wetland clonal plant in the Araliaceae family, which was introduced to China as an ornamental plant in the 1990s. Although H. vulgaris is now considered a potential invasiveness species in China, it also plays a significant role in the remediation of water pollution. Here, we reported its complete chloroplast genome and analyzed the basic characteristics. The chloroplast genome was 153,165 bp in length, including a pair of inverted repeat (IR) regions of 25,072 bp separated by a large single-copy (LSC) region of 84,291 bp and a small single-copy (SSC) region of 18,730 bp. The H. vulgaris chloroplast genome contained 132 predicted genes, and its overall GC content was 37.60%. Phylogenetic analysis revealed that H. vulgaris was closely related to H. verticillata. The H. vulgaris chloroplast genome presented in this study will lay a foundation for further genetic and genomic studies of the genus Hydrocotyle.

Paraquat and MPTP induce alteration in the expression profile of long noncoding RNAs in the substantia nigra of mice: Role of the transcription factor Nrf2.

Parkinson's disease (PD) is a common age-related degenerative disease of the central nervous system caused mainly by hereditary, pesticides, metals, and polychlorinated biphenyls. Paraquat (PQ), a widely used herbicide, causes PD. Long noncoding RNAs (lncRNAs) are nonprotein-coding transcripts, expressed in the brain and play irreplaceable roles in neurodegenerative diseases. NF-E2-related factor-2 (Nrf2) is an important genetic transcription regulator in oxidative stress. We aimed to discover novel PQ or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-Nrf2-related lncRNAs and explore their association with PD. 17157 lncRNAs and 13707 mRNAs (fold change ≥2, P < 0.05) were identified by Microarray. And the expressions of six lncRNAs were confirmed by using qRT-PCR and two by FISH. Coding-noncoding analysis and qRT-PCR were applied to discover the functions of lncRNAs and predict the targeted genes. In mice, PQ and MPTP exposure caused alteration of the lncRNA expression profile, suggesting lncRNAs may be involved in PQ- and MPTP-induced neurotoxicity. The changes in their lncRNA expression were distinct but related. PQ caused lncRNA expression profiling alteration in the substantia nigra (SN) through an interaction with Nrf2, thus changing the NR_027648/Zc3h14/Cybb and NR_030777/Zfp326/Cpne5 mRNA pathways. Similarly, MPTP caused lncRNA expression profiling alteration in SN through an interaction with Nrf2. Nrf2 may be involved in the development of neurodegeneration induced by PQ and MPTP via interaction with lncRNAs as the molecular mechanism. Our findings indicate the potential roles of lncRNAs in the development of PD by PQ or MPTP and provide positive insights into future mechanism studies.

Solution-Processed Cu9S5 as a Hole Transport Layer for Efficient and Stable Perovskite Solar Cells.

Organic-inorganic perovskite solar cells have seen tremendous developments in recent years. As a hole transport material, 2,2',7,7'-tetrakis( N, N-di- p-methoxyphenylamine)-9,9'-spirobifluorene (Spiro-OMeTAD) is widely used in n-i-p perovskite solar cells. However, it may lead to the perovskite film degradation due to the dopant lithium bis((trifluoromethyl)sulfonyl)amide (Li-TFSI), which has strong hydrophilicity. Cu9S5 is considered as a superior p-type transport material, which also has a favorable energy level matching with the highest occupied molecular orbital of Spiro-OMeTAD. Herein, a solution-processed organic-inorganic-integrated hole transport layer was reported, which is composed of the undoped Spiro-OMeTAD and Cu9S5 layer. Since there is no Li-TFSI doping, it is extremely conductive to the long-term stability of the solar cells. In the meantime, we proposed a method to adjust the lowest unoccupied molecular orbital (LUMO) of SnO2 via nitrogen implantation (N:SnO2). The LUMO of SnO2 can be tuned from -4.33 to -3.91 eV, which matches well with the LUMO of CH3NH3PbI3 (-3.90 eV), and thus helps to reduce hysteresis. The modified hole and electron transport layers were applied in n-i-p perovskite solar cells, which achieve a maximum power conversion efficiency (PCE) of 17.10 and 96% retention of PCE after 1200 h in air atmosphere without any encapsulation.

The Dawn of Lead-Free Perovskite Solar Cell: Highly Stable Double Perovskite Cs2AgBiBr6 Film.

Recently, lead-free double perovskites have emerged as a promising environmentally friendly photovoltaic material for their intrinsic thermodynamic stability, appropriate bandgaps, small carrier effective masses, and low exciton binding energies. However, currently no solar cell based on these double perovskites has been reported, due to the challenge in film processing. Herein, a first lead-free double perovskite planar heterojunction solar cell with a high quality Cs2AgBiBr6 film, fabricated by low-pressure assisted solution processing under ambient conditions, is reported. The device presents a best power conversion efficiency of 1.44%. The preliminary efficiency and the high stability under ambient condition without encapsulation, together with the high film quality with simple processing, demonstrate promise for lead-free perovskite solar cells.

Production and anti-diabetic activity of soluble dietary fiber from apricot pulp by Trichoderma viride fermentation.

Soluble dietary fiber (SDF) was prepared by Trichoderma viride fermentation by using apricot pulp as the raw material. A four-factor and three-level response surface methodology was applied to optimize the fermentation conditions affecting the extraction rate of SDF. The optimum fermentation conditions were listed: crude enzyme volume, 9.59 mL g(-1); fermentation temperature, 43 °C; initial pH, 5.36; fermentation time, 6.47 h. Under these conditions, 15.69% yield was obtained and its relative error with the predicted theoretical value (15.87%) was 1.14%. The dietary fiber content of SDF was 84.0% whereas it was found to be 43.1% in apricot pulp flour. The anti-diabetic effect of apricot pulp SDF on rat models of diabetes was investigated. Both the blood glucose level and body weight were significantly changed in apricot pulp SDF-treated groups compared with the diabetic group (p < 0.01) after intragastric administration for 28 days. In addition, SDF elicited inhibitory effects on the α-glucosidase activity with an IC50 of 17.458 mg mL(-1). These results implied that apricot pulp SDF relieved the symptoms of diabetic rats.

Comparison of physical properties of regenerated cellulose films fabricated with different cellulose feedstocks in ionic liquid.

With the serious "white pollution" resulted from the non-biodegradable plastic films, considerable attention has been directed toward the development of renewable and biodegradable cellulose-based film materials as substitutes of petroleum-derived materials. In this study, environmentally friendly cellulose films were successfully prepared using different celluloses (pine, cotton, bamboo, MCC) as raw materials and ionic liquid 1-ethyl-3-methylimidazolium acetate as a solvent. The SEM and AFM indicated that all cellulose films displayed a homogeneous and smooth surface. In addition, the FT-IR and XRD analysis showed the transition from cellulose I to II was occurred after the dissolution and regeneration process. Furthermore, the cellulose films prepared by cotton linters and pine possessed the most excellent thermal stability and mechanical properties, which were suggested by the highest onset temperature (285°C) and tensile stress (120 MPa), respectively. Their excellent properties of regenerated cellulose films are promising for applications in food packaging and medical materials.

Experimental study on transient behavior of semi-open two-phase thermosyphon.

An experimental system was set up to measure the temperature, pressure, heat transfer rate and mass flow rate in a semi-open two-phase thermosyphon. The behaviors of a semi-open two-phase thermosyphon during startup, shutdown and lack of water were studied to get complete understanding of its thermal characteristics. The variation of wall temperature, heat-exchange condition and pressure fluctuations of semi-open two-phase thermosyphons showed that the startup of SOTPT needs about 60-70 min; the startup speed of SOTPT is determined by the startup speed of the condensation section; the average pressure in the heat pipe is equal to the environmental pressure usually; the shutdown of SOTPT needs about 30-50 min; a semi-open two-phase thermosyphon has good response to lack of water accident.

A study on workplace violence and its effect on quality of life among medical professionals in China.

The present study was conducted to investigate workplace violence and to examine how it is associated with quality of life (QOL) among medical professionals in China. A total of 2,464 medical professionals were selected from Fujian Province and Henan Province by using stratified cluster-sampling method. A Chinese version of the workplace violence scale was used to measure the incidence of workplace violence. The Short Form-36 Health Survey was employed to assess their QOL. Approximately 50% of the participants reported at least one type of workplace violence occurring in the previous 12 months. The multivariate analysis demonstrated workplace violence as a significant predictor for QOL among medical professionals, after controlling for other potential predictors. It suggests that the implementation of violence prevention policies and strategies to reduce workplace violence may improve QOL of medical professionals in China.