Identification of candidate genes involved in wax deposition in Poa pratensis by RNA-seq

A, Randomness test of cDNA fragments; B, Sequencing saturation analysis. T1 and T2 represent NEZm; T3 and T4 represent EBZ. (PDF 290 kb

Revisiting Scalarization in Multi-Task Learning: A Theoretical Perspective

Linear scalarization, i.e., combining all loss functions by a weighted sum, has been the default choice in the literature of multi-task learning (MTL) since its inception. In recent years, there is a surge of interest in developing Specialized Multi-Task Optimizers (SMTOs) that treat MTL as a multi-objective optimization problem. However, it remains open whether there is a fundamental advantage of SMTOs over scalarization. In fact, heated debates exist in the community comparing these two types of algorithms, mostly from an empirical perspective. To approach the above question, in this paper, we revisit scalarization from a theoretical perspective. We focus on linear MTL models and study whether scalarization is capable of fully exploring the Pareto front. Our findings reveal that, in contrast to recent works that claimed empirical advantages of scalarization, scalarization is inherently incapable of full exploration, especially for those Pareto optimal solutions that strike the balanced trade-offs between multiple tasks. More concretely, when the model is under-parametrized, we reveal a multi-surface structure of the feasible region and identify necessary and sufficient conditions for full exploration. This leads to the conclusion that scalarization is in general incapable of tracing out the Pareto front. Our theoretical results partially answer the open questions in Xin et al. (2021), and provide a more intuitive explanation on why scalarization fails beyond non-convexity. We additionally perform experiments on a real-world dataset using both scalarization and state-of-the-art SMTOs. The experimental results not only corroborate our theoretical findings, but also unveil the potential of SMTOs in finding balanced solutions, which cannot be achieved by scalarization.Comment: Accepted at NeurIPS 202

Species-Specific Expansion and Molecular Evolution of the 3-hydroxy-3-methylglutaryl Coenzyme A Reductase (HMGR) Gene Family in Plants

Kazakh dandelion (Taraxacum kok-saghyz, Tk) is a rubber-producing plant currently being investigated as a source of natural rubber for industrial applications. Like many other isoprenoids, rubber is a downstream product of the mevalonate pathway. The 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) enzyme catalyzes the conversion of 3-hydroxy-3-methylglutaryl-CoA to mevalonic acid, a key regulatory step in the MVA pathway. Such regulated steps provide targets for increases in isoprenoid and rubber contents via genetic engineering to increase enzyme activities. In this study, we identify a TkHMGR1 gene that is highly expressed in the roots of Kazakh dandelion, the main tissue where rubber is synthesized and stored. This finding paves the way for further molecular and genetic studies of the TkHMGR1 gene, and its role in rubber biosynthesis in Tk and other rubber-producing plants

Perceptions of clinicians and research ethics boards regarding ethical issues in investigator-initiated trials: a multicenter qualitative study in China

Purpose: This multicenter qualitative study aimed to explore the perceptions of clinicians and research ethics boards (REBs) regarding ethical issues in Investigator Initiated Trials (IITs). Methods: Between February and April 2024, semi-structured interviews were conducted with 27 participants from 15 tertiary hospitals, including clinical doctors and members of REBs. Responses were grouped and analyzed using a descriptive phenomenological approach. Results: Clinicians expressed challenges in navigating the formal review process due to limited access to information and unclear guidelines. Academic review highlighted a deficiency in research literacy among clinical investigators, leading to flawed study design. Ethical review revealed concerns about inadequate ethical awareness among clinicians, resulting in failed ethical approvals. Moreover, delays in review processes and resource shortages were noted, hindering the efficient conduct of IITs. Conclusion: The findings underscore the need for comprehensive training programs to enhance clinicians’ research literacy and ethical awareness. Establishing a comprehensive system to support IITs, including enhanced guidance and support from REBs, is essential to ensure the quality and integrity of IITs in China

Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for patients with unresectable hepatocellular carcinoma: a cost–utility analysis in China and the United States

ObjectiveCamrelizumab plus rivoceranib (camr-rivo) has been shown to significantly improve overall survival (OS) in patients with unresectable or advanced hepatocellular carcinoma (HCC) in the CARES-310 trial. However, the cost-utility of this treatment remains unclear. Therefore, this study evaluated the cost–utility of camr-rivo versus sorafenib as a first-line systemic therapy for patients with unresectable or advanced HCC from the perspectives of the Chinese healthcare system and the United States (US) payers.MethodsBased on the CARES-310 trial, a partitioned survival model was constructed to estimate economic costs and health outcomes over a 10-year lifetime horizon. Drug costs were obtained from the public database, Red Book, and relevant literature. Health utility values were derived from the literature. One-way and probabilistic sensitivity analyses were performed. The willingness-to-pay (WTP) threshold was $36,627.25/QALY in China and$150,000.00/QALY in the United States.ResultsCamr-rivo yielded an additional 0.34 quality-adjusted life years (QALY) compared to sorafenib for patients with unresectable or advanced HCC. The incremental costs in China and the United States were $4,762.10 and$92,700.49, respectively, and the incremental cost–utility ratios (ICURs) were $14,174.40/QALY and$272,852.59/QALY, respectively. Sensitivity analyses indicated that the cost of rivoceranib and camrelizumab had the greatest impact on the ICUR in China and the United States. Scenario analyses showed that a price reduction of approximately 30% for camrelizumab and rivoceranib could make camr-rivo a cost-utility option in the United States.ConclusionAt the set WTP threshold, camr-rivo is a cost–utility treatment strategy compared to sorafenib as a first-line therapy for patients with unresectable or advanced HCC in China but not in the United States

Influence of anionic species on the low temperature pyrolysis performance of heated tobacco sheets catalyzed by sodium salts

Development of low temperature catalytic pyrolysis technology for heated tobacco sheets is expected to increase the aroma of heated tobacco products and improve their overall smoking quality. In this study, the low temperature pyrolysis performances of heated tobacco sheets catalyzed by various anionic sodium salts were investigated using TG-DTG, Py-GC-MS technology and smoke routine chemical composition analysis. The results showed that the total weight loss between 100°C and 300°C increased by 7.8%–13.15% after adding various anionic sodium salts, among which, sodium acetate and sodium tartrate showed a relatively higher weight loss. The relative content of free hydroxyacetone, furfuryl alcohol, butyrolactone and megastigmatrienone in the pyrolysis gas increased, while the relative content of free nicotine decreased. With the change of anionic species, the catalytic decomposition ability of cellulose, lignin, and other substances may change, resulting in the distribution alteration of compounds in the pyrolysis gas. After adding sodium acetate and sodium citrate, the release of total particulate matter (TPM), glycerol, and nicotine in flue gas increased. Overall, the addition of sodium acetate and sodium citrate showed a higher low temperature pyrolysis performance of heated tobacco sheets. The research results in this paper provide data support for changing the low temperature catalytic pyrolysis performance of heated tobacco sheets by adjusting the type of anions in sodium salts

Bacteroides fragilis capsular polysaccharide A ameliorates ulcerative colitis in rat by recovering intestinal barrier integrity and restoring gut microbiota

Bacteroides fragilis (B. fragilis) is a Gram-negative, obligate anaerobic, commensal bacterium residing in the human gut and holds therapeutic potential for ulcerative colitis (UC). Previous studies have indicated that capsular polysaccharide A (PSA) of B. fragilis is a crucial component for its effectiveness, possessing various biological activities such as anti-inflammatory, anti-tumor, and immune-modulating effects. We previously isolated and characterized the B. fragilis strain ZY-312 from the feces of a healthy breastfed infant, and extracted its PSA, named TP2. In this study, we explored the impact of TP2 on colonic inflammation and delved into its potential mechanisms. Initially, we used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce colitis in rats and found that TP2 treatment significantly ameliorated TNBS-induced weight loss, increased clinical scores, extensive ulcers, and intestinal epithelial damage in UC rats. Further analysis revealed that TP2 effectively restored the intestinal barrier integrity in UC rats by regulating the expression of Muc-2, tight junction proteins (ZO-1, occludin, claudin-1, and claudin-2), as well as apoptosis-related proteins Bcl-2, BAX, and Cleaved-Caspase-3. Additionally, TP2 suppressed the expression of pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and IL23, while promoting the secretion of anti-inflammatory cytokines IL-10 and IL-22, thereby inhibiting the occurrence of inflammation. TP2 also downregulated the phosphorylation levels of AKT and PI3K, effectively inhibiting the abnormal activation of the PI3K/AKT signaling pathway. More interestingly, 16S rRNA sequencing results showed that TP2 restored the ecological imbalance of the rat intestinal microbiota, with an increase in beneficial bacteria such as Lactobacillus and Limosilactobacillus observed in the treatment group. In conclusion, TP2 through the regulation of intestinal barrier-related cells and proteins, inhibition of apoptosis, modulation of inflammation-related cytokine levels, and control of abnormal activation of the PI3K/AKT signaling pathway, restores intestinal barrier integrity. Additionally, by reshaping the ecological imbalance of the gut microbiota, TP2 ultimately alleviates ulcerative colitis in rats

Effects of microbial fermentation on the anti-inflammatory activity of Chinese yam polysaccharides

In this study, Chinese yam polysaccharides (CYPs) were fermented using Lactobacillus plantarum M616, and changes in the chemical composition, structure, and anti-inflammatory activity of CYPs before and after fermentation were investigated. The carbohydrate content of L. plantarum M616-fermented CYP (CYP-LP) increased from 71.03% ± 2.75 to 76.28% ± 2.37%, whereas protein and polyphenol content were almost unaffected compared with those of the unfermented CYP (CYP-NF). The monosaccharide composition of CYP-NF included rhamnose, arabinose, galactose, glucose, and mannose in a molar ratio of 0.493:0.6695:0.9738:0.7655:12.4365. CYP-LP had the same monosaccharides as CYP-NF, but the molar ratio was 0.3237:0.3457:0.8278:2.5541:10.4995. Meanwhile, the molecular weight and polydispersity of CYP-LP, respectively, increased from 124.774 kDa and 6.58 (CYP-NF) to 376.628 kDa and 17.928, indicating a low homogeneity. In vitro antioxidant analysis showed that L. plantarum M616 fermentation had varying effects on CYP-LP against DPPH, ABTS, hydroxyl, and superoxide radicals. However, CYP-LP had superior anti-inflammatory activity to CYP-NF and is more effective in regulating superoxide dismutase, catalase, glutathione peroxidase, malondialdehyde, nitric oxide, tumor necrosis factor-α, interleukin-1β, and interleukin-6 release in lipopolysaccharide-induced RAW 264.7 macrophages. This study suggested that CYP-LP is a potential anti-inflammatory ingredient in drugs and functional food

Sexually transmitted infections and semen quality from subfertile men with and without leukocytospermia

Background: The role of sexually transmitted infections (STIs) in semen parameters and male infertility is still a controversial area. Previous studies have found bacterial infection in a minority of infertile leukocytospermic males. This study aims to investigate the prevalence of STIs in semen from subfertile men with leukocytospermia (LCS) and without leukocytospermia (non-LCS) and their associations with sperm quality. Methods: Semen samples were collected from 195 men who asked for a fertility evaluation. Infection with the above 6 pathogens was assessed in each sample. Sperm quality was compared in subfertile men with and without LCS. Results: The LCS group had significantly decreased semen volume, sperm concentration, progressive motility, total motility and normal morphology. The infection rates of Ureaplasma urealyticum (Uuu), Ureaplasma parvum (Uup), Mycoplasma hominis (MH), Mycoplasma genitalium (MG), Chlamydia trachomatis (CT), herpes simplex virus-2 (HSV-2) and Neisseria gonorrhoeae (NG) were 8.7 %, 21.0 %, 8.2 %, 2.1 %, 3.6 %, 1.0 and 0 %, respectively. The STI detection rates of patients with LCS were higher than those of the non-LCS group (52.3 % vs. 39.3 %), although there was no statistically significant difference between the two groups (P = 0.07). All semen parameters were not significantly different between LCS with STIs and without STIs, except the semen volume in the MG-infected patients with LCS was significantly lower than that in the noninfected group. Conclusions: LCS was associated with a reduction in semen quality, but was not associated with STIs