Leverage machine learning to identify key measures in hospital operations management: a retrospective study to explore feasibility and performance of four common algorithms.

BACKGROUND: Measures in operations management are pivotal for monitoring and assessing various aspects of hospital performance. Existing literature highlights the importance of regularly updating key management measures to reflect changing trends and organizational goals. Advancements in machine learning (ML) have presented promising opportunities for enhancing the process of updating operations management measures. However, their specific application and performance remain relatively unexplored. We aimed to investigate the feasibility and effectiveness of using common ML techniques to identify and update key measures in hospital operations management. METHODS: Historical data on 43 measures on financial balance and quality of care under 4 categories were retrieved from the BI system of a regional health system in Central China. The dataset included 17 surgical and 15 non-surgical departments over 48 months. Four common ML techniques, linear models (LM), random forest (RF), partial least squares (PLS), and neural networks (NN), were used to identify the most important measures. Ordinary least square was employed to investigate the impact of the top 10 measures. A ground truth validation compared the ML-identified key measures against the humanly decided strategic measures from annual meeting minutes. RESULTS: For financial balancing, inpatient treatment revenue was an important measure in 3/4 years, followed by equipment depreciation costs. The measures identified using the same technique differed between years, though RF and PLS yielded relatively consistent results. For quality of care, none of the ML-identified measures repeated over the years. Those consistently important over four years differed almost entirely among four techniques. On ground truth validation, the 2016-2019 ML-identified measures were among the humanly identified measures, with the exception of equipment depreciation from the 2019 dataset. All the ML-identified measures for quality of care failed to coincide with the humanly decided measures. CONCLUSIONS: Using ML to identify key hospital operational measures is viable but performance of ML techniques vary considerably. RF performs best among the four techniques in identifying key measures in financial balance. None of the ML techniques seem effective for identifying quality of care measures. ML is suggested as a decision support tool to remind and inspire decision-makers in certain aspects of hospital operations management.

Toripalimab combined with definitive chemoradiotherapy for locally advanced cervical squamous cell carcinoma patients (TRACE): A single-arm, phase I/II trial.

PURPOSE: This phase I/II trial (ChiCTR2000032879) assessed the safety and efficacy of toripalimab combined with chemoradiotherapy for locally advanced cervical squamous cell carcinoma. METHODS AND MATERIALS: Twenty-two patients, regardless of their programmed death ligand-1 (PD-L1) status, received toripalimab combined with concurrent chemoradiotherapy (CCRT). CCRT included cisplatin (40 mg/m2, once weekly for 5 weeks), radiotherapy (45-50.4 Gy/25-28 Fx, 5 fractions weekly), followed by brachytherapy (24-30 Gy/3-5 Fx) and toripalimab (240 mg, intravenous) on days 1, 22 and 43 during CCRT. The primary endpoints were safety and 2-year progression-free survival (PFS). The secondary endpoints included 2-year local control (LC), local regional control and overall survival (OS). RESULTS: All patients successfully completed CCRT and toripalimab treatment. Grade III and higher adverse events (AEs) were observed in 11 patients (11/22, 50%), and no patient experienced grade V AEs. The objective response rate (ORR) was 100%. At the data cutoff (June 30, 2023), the median follow-up was 31.8 months (9.5 to 37.8 months). The 2-year PFS rate was 81.8%. The 2-year LC and local regional control rates were both 95.5%, and the 2-year OS rate was 90.9%. CONCLUSIONS: Toripalimab combined with CCRT achieved good tolerance and showed promising anti-tumor effects in patients with locally advanced cervical cancer.

Copper-catalyzed tandem cyclization reaction of ethynylbenzoxazinones and thiols: facile construction of 2-thiomethylene indoles.

The first successful copper-catalyzed decarboxylative cyclization reaction of ethynylbenzoxazinones and thiols has been developed. A rarely studied α-addition process to a copper-allenylidene intermediate promoted this reaction. Using this protocol, a range of 2-thiomethylene indole compounds have been obtained. This methodology offers significant advantages including mild reaction conditions, cheap catalysts, good yields and broad substrate compatibility.

[AI-HIP system for prosthesis size, global femoral offset and osteotomy in total hip arthroplasty].

OBJECTIVE: To explore planning effect of AI-HIP assisted surgical planning system in primary unilateral total hip arthroplasty (THA) and its influence on clinical outcomes. METHODS: A retrospective analysis was conducted on clinical data of 36 patients who underwent their first unilateral THA from March 2022 to November 2022 and continuously used AI-HIP system (AI-HIP group), including 16 males and 20 females, aged from 43 to 81 years old with an average of (62.2±10.9) years old. According to the matching principle, 36 patients who were planned by the traditional template method at the same period were selected as the control group, including 16 males and 20 females, aged from 40 to 80 years old with an average of (60.9±12.1) years old. The accuracy between two groups of prostheses were compared, as well as the combined eccentricity difference between preoperative planning and postoperative practice, lower limb length difference, osteotomy height from the upper edge of the lesser trochanter and top shoulder distance to evaluate planning effect. Harris score and visual analogue scale (VAS) were used to evaluate clinical efficacy. RESULTS: Both groups were followed up for 12 to 18 months with an average of (14.5±2.1) months. The complete accuracy and approximate accuracy of acetabular cup and femoral stalk prosthesis in AI-HIP group were 72.2%, 100%, 58.3%, 88.9%, respectively, which were better than 44.4%, 83.3%, 33.3%, 66.7% in control group (P<0.05). There was no statistical significance in planning of femoral head prosthesis size (P>0.05). The actual combined eccentricity difference and combined eccentricity difference (practical-planning) in AI-HIP group were 1.0(0.2, 2.4) mm and 1.1(-2.1, 3.2) mm, respectively;which were better than 3.0 (1.4, 4.9) mm and 3.5 (-1.6, 6.5) mm in control group (P<0.05). There was no significant difference between two groups in actual osteotomy height of the upper margin of the lesser trochanter (P>0.05). In AI-HIP group, the actual difference of lower extremity length after surgery, the difference of lower extremity length (practical-planning), osteotomy height from the upper margin of lesser trochanter (practical-planning), actual topshoulder distance after surgery, and topshoulder distance (practical-planning) were 1.5 (0.2, 2.8), 1.1 (-0.3, 2.2), 2.1(-2.3, 4.1), (15.3±4.1), 2.2(-4.8, 0.3) mm, respectively;which were better than control group of 2.6(1.3, 4.1), 2.5 (0.3, 3.8), 5.8(-2.4, 7.7), (13.0±4.3), -5.7(-9.4, -2.2) mm(P<0.05). At final follow-up, there were no significant differences in Harris scores of pain, function, deformity, total scores and VAS between two groups (P>0.05). The range of motion score was 4.8±0.6 in AI-HIP group, which was higher than that in control group (4.4±0.8)(P<0.05). CONCLUSION: Compared with traditional template planning, AI-HIP assisted surgical planning system has good accuracy in predicting the prosthetic size of the acetabular cup and femoral stalk, restoring joint eccentricity, planning lower limb length, osteotomy height and top shoulder distance on the first unilateral THA, and the clinical follow-up effect is satisfactory.

BRCA1 promotes repair of DNA damage in cochlear hair cells and prevents hearing loss.

Cochlear hair cells (HCs) sense sound waves and allow us to hear. Loss of HCs will cause irreversible sensorineural hearing loss. It is well known that DNA damage repair plays a critical role in protecting cells in many organs. However, how HCs respond to DNA damage and how defective DNA damage repair contributes to hearing loss remain elusive.In this study, we showed that cisplatin induced DNA damage in outer hair cells (OHCs) and promoted OHC loss, leading to hearing loss in mice of either sex. Cisplatin induced the expression of Brca1, a DNA damage repair factor, in OHCs. Deficiency of Brca1 induced OHC and hearing loss, and further promoted cisplatin-induced DNA damage in OHCs, accelerating OHC loss. This study provides the first in vivo evidence demonstrating that cisplatin mainly induces DNA damage in OHCs and that BRCA1 promotes repair of DNA damage in OHCs and prevents hearing loss. Our findings not only demonstrate that DNA-damage inducible agent generates DNA damage in postmitotic HCs, but also suggest that DNA repair factors, like BRCA1, protect postmitotic HCs from DNA-damage induced cell death and hearing loss.Significance statement Sensorineural hearing loss is the most severe hearing loss caused by irreversible loss of cochlear hair cells. Hair cells are vulnerable to aging and ototoxic drug. Though DNA damage repair plays a critical role in protecting cells in many organs, it is poorly understood how DNA damage is repaired in hair cells. This study provides the first in vivo evidence demonstrating that cisplatin mainly induces DNA damage in outer hair cells and that BRCA1 promotes repair of DNA damage in outer hair cells and prevents outer hair cell loss as well as hearing loss.

Effects of lower-limb active resistance exercise on mobility, physical function, knee strength and pain intensity in patients with total knee arthroplasty: a systematic review and meta-analysis.

BACKGROUND: Total knee arthroplasty (TKA) successfully alleviates pain from knee osteoarthritis, but muscle strength and function are reduced for a long period postoperatively. Postoperative active resistance exercise may play a relevant role. PURPOSE: To systematically evaluate effects of lower-limb active resistance exercise (ARE) on mobility, physical function, muscle strength and pain intensity in patients with TKA. METHODS: A search was conducted in PubMed, EMBASE, and Cochrane Library databases from inception to September 2023. Only randomized controlled trials (RCTs) that compared the effects of ARE and no intervention or other rehabilitation program without PRE were included. The outcome variables were mobility (Maximal walking speed [MWS]/6-Minute Walk Test[6MWT]), physical function (Stair Climb Test [SCT]/Timed Up and Go [TUG]), knee extension/ flexion power(KEP/KFP), joint range of motion (ROM) and pain. Standardized Mean Differences (SMD) or Mean Differences (MD) and 95% confidence intervals (CI) were calculated and combined in meta-analyses. The Cochrane Collaboration's Handbook were used for the methodological quality assessments. GRADE was used to assess the quality of evidence. The meta-analysis was performed using the RevMan 5.4 software. RESULTS: A total of 14 randomized controlled trials, involving 880 patients, were finally included. The lower-limb ARE exhibited significantly greater improvement in MWS (MD 0.13, 95%CI 0.08-0.18, P < 0.00001), TUG(MD -0.92, 95%CI -1.55- -0.28, P = 0.005), KEP (SMD 0.58, 95%CI 0.20-0.96, P = 0.003), KFP (SMD 0.38, 95%CI 0.13-0.63, P = 0.003), ROM-flexion (MD 2.74, 95%CI 1.82-3.67, P < 0.00001) and VAS (MD - 4.65, 95% CI - 7.86- -1.44, p = 0.005) compared to conventional exercise(CE) immediately post-intervention. However, there were no statistically significant differences between both groups in regard to 6MWT (MD 7.98, 95%CI -4.60-20.56, P = 0.21), SCT (MD -0.79, 95%CI -1.69-0.10, P = 0.08) and ROM-extension (MD -0.60, 95%CI -1.23-0.03, P = 0.06). CONCLUSIONS: According to the results of meta-analysis, patients undergoing TKA who receive the lower extremity ARE show better clinical effects in terms of pain relief, strength recovery and knee ROM. Simultaneously, it may be beneficial to improve mobility and physical function of patients after TKA.

Integrative analysis of miRNA profile and degradome reveals post-transcription regulation involved in fragrance formation of Rosa rugosa.

Rosa rugosa is renowned for its fragrant essential oils (EOs) including the primary volatile compounds such as terpenes (geraniol and citronellol) and 2-phenylethanol. While the role of miRNAs in plant secondary metabolism has been explored, their involvement in EOs metabolism remains largely unknown. Sequencing of the petals of R. rugosa identified 383 conserved miRNAs and 625 novel miRNAs including 53 miRNAs differentially expressed in a strong fragrance variety R. rugosa 'White Purple Branch'. Degradome sequencing predicted 1969 targets enriched in GO terms involved in the negative regulation of macromolecule metabolic process. Furthermore, 122 targets of differentially expressed miRNAs were enriched in phenylalanine metabolism and other KEGG pathways. A post-transcriptional regulation network of 52 miRNAs and 70 miRNA-transcription factor modules target terpene and 2-phenylethanol biosynthesis pathways. Six interactions including miR535f-RrHMGR, NOV146-RrNUDX1, miR166l-RrHY5 and miR156c-RrSPL2 were validated using RNA ligase-mediated RACE. Sequence alignment revealed that the NOV146-RrNUDX1 was conserved in the Rosa genus. Moreover, weaker silencing of RrNUDX1 by NOV146 contributed to the stronger fragrance of R. rugosa. These findings offer a comprehensive understanding of the post-transcriptional regulation involved in essential oil biosynthesis and identify candidate miRNAs for further genetic improvement of EO yields in R. rugosa.

Metabolite and Transcriptome Profiling Analysis Provides New Insights into the Distinctive Effects of Exogenous Melatonin on Flavonoids Biosynthesis in Rosa rugosa.

Although the petals of Rosa rugosa are rich in flavonoids and their bioactivity has a significant impact on human health, the flavonoid content decreases during flower development. In this study, R. rugosa 'Feng hua' was used to investigate the effects of the melatonin foliar spray on enhancing the quality of rose by focusing on major flavonoids. The results showed that the contents of total flavonoids in rose petals at the full bloom stage induced by melatonin obeyed a bell-shaped curve, with a maximum at 0.3 mM, indicating the concentration-dependent up-regulation of flavonoid biosynthesis. In the treatment with 0.3 mM melatonin, metabolomic analyses showed that the concentrations of ten main flavonoids were identified to be increased by melatonin induction, with high levels and increases observed in three flavonols and two anthocyanins. KEGG enrichment of transcriptomic analysis revealed a remarkable enrichment of DEGs in flavonoid and flavonol biosynthesis, such as Rr4CL, RrF3H, and RrANS. Furthermore, functional validation using virus-induced gene silencing technology demonstrated that Rr4CL3 is the crucial gene regulating flavonoid biosynthesis in response to the stimulant of melatonin. This study provides insights into the exogenous melatonin regulation mechanism of biosynthesis of flavonoids, thereby offering potential industrial applications.

The Integrated Analysis of miRNome and Degradome Sequencing Reveals the Regulatory Mechanisms of Seed Development and Oil Biosynthesis in Pecan (Carya illinoinensis).

Pecan seed oil is a valuable source of essential fatty acids and various bioactive compounds; however, the functions of microRNAs and their targets in oil biosynthesis during seed development are still unknown. Here, we found that the oil content increased rapidly in the three early stages in three cultivars, and that oleic acid was the predominant fatty acid component in the mature pecan embryos. We identified, analyzed, and validated the expression levels of miRNAs related to seed development and oil biosynthesis, as well as their potential target genes, using small RNA sequencing data from three stages (120, 135, and 150 days after flowering). During the seed development process, 365 known and 321 novel miRNAs were discovered. In total, 91 known and 181 novel miRNAs were found to be differentially expressed, and 633 target genes were further investigated. The expression trend analysis revealed that the 91 known miRNAs were classified into eight groups, approximately two-thirds of which were up-regulated, whereas most novel miRNAs were down-regulated. The qRT-PCR and degradome sequencing data were used to identify five miRNA- target pairs. Overall, our study provides valuable insights into the molecular regulation of oil biosynthesis in pecan seeds.

Lateral flow chromatography strip system for rapid fluorescence determination of phycocyanin in water samples.

Phycocyanin (PC) is of great significance to biomedicine and water environmental safety. Hence, it is indispensable to develop facile and rapid method for PC determination. In this investigation, a system containing lateral flow chromatography (LFC) strip (which was deposited with molecularly imprinted polymer (MIP) capped CdTe quantum dots (QDs) based mesoporous structured coated silica nanoparticles, SiO2@QDs@ms-MIP NPs) and miniaturized fluorimeter was first fabricated. In detail, a two-step strategy was utilized for preparation of SiO2@QDs@ms-MIP NPs, which consisted of modification of CdTe QDs onto the silica NPs first, and synthesis of mesoporous imprinting shell by using PC as template molecule and cetyltrimethylammonium bromide (CTAB) as surfactant. After that, novel fluorescence NPs possessing specific recognition and sensitivity toward PC in seawater and lake water were acquired. The resulting fluorescent sensing system exhibited outstanding performances, which included excellent sensitivity (4.5 nmol/L), satisfactory specificity (imprinting factor, 2.31), appropriate linearity range (0.01-5 µmol/L), good recovery (96.0-101.7 %), excellent stability (relative standard deviation, RSD<1.1 %), wonderful reproducibility (RSD<1.1 %), and excellent anti-interference ability. The results of the fluorescent sensing system were superior to those of the commonly used ultraviolet (UV) method. The proposed strategy showed great potential for fast (<10 min) and convenient fluorescence detection of PC in real samples.

USP11 deubiquitinates E-cadherin and maintains luminal fate of mammary tumor cells to suppress breast cancer.

Basal-like breast cancer may originate from luminal epithelial or cancerous cells. Inadequately repaired DNA damage impairs luminal differentiation and promotes aberrant luminal to basal trans-differentiation in mammary epithelial cells (MECs). Ubiquitin-specific peptidase 11 (USP11), a deubiquitinase, plays a critical role in DNA damage repair. The role of USP11 in controlling mammary cell differentiation and tumorigenesis remains poorly understood. We generated Usp11 knockout mice and breast cancer cell lines expressing wild-type (WT) and mutant form of USP11. By using these mutant mice, cell lines, and human USP11-deficient and -proficient breast cancer tissues, we tested how USP11 controls mammary cell fate. We generated Usp11 knock-out mice and found that deletion of Usp11 reduced the expression of E-cadherin and promoted DNA damage in MECs. Overexpression of WT USP11, but not a deubiquitinase-inactive mutant form of USP11, promoted luminal differentiation, enhanced DNA damage repair, and suppressed tumorigenesis in mice. Mechanistically, we found that USP11 enhanced the protein expression of E-cadherin dependent on its deubiquitinase activity, and that USP11 deubiquitinated E-cadherin at K738. We discovered that USP11 bound to E-cadherin through its C-terminal region. In human breast cancers, expression of USP11 was positively correlated with that of E-cadherin, and high USP11 predicted better recurrence-free survival. Our findings provide compelling genetic and biochemical evidence that USP11 not only promotes DNA damage repair but also deubiquitinates E-cadherin and maintains the luminal feature of mammary tumor cells, thereby suppressing luminal breast cancer.

Discovery of Novel PROTAC SIRT6 Degraders with Potent Efficacy against Hepatocellular Carcinoma.

Sirtuin 6 (SIRT6), a member of the SIRT family, plays essential roles in the regulation of metabolism, inflammation, aging, DNA repair, and cancer development, making it a promising anticancer drug target. Herein, we present our use of proteolysis-targeting chimera (PROTAC) technology to formulate a series of highly potent and selective SIRT6 degraders. One of the degraders, SZU-B6, induced the near-complete degradation of SIRT6 in both SK-HEP-1 and Huh-7 cell lines and more potently inhibited hepatocellular carcinoma (HCC) cell proliferation than the parental inhibitors. In preliminary mechanistic studies, SZU-B6 hampered DNA damage repair, promoting the cellular radiosensitization of cancer cells. Our SIRT6 degrader SZU-B6 displayed promising antitumor activity, particularly when combined with the well-known kinase inhibitor sorafenib or irradiation in an SK-HEP-1 xenograft mouse model. Our results suggest that these PROTACs might constitute a potent therapeutic strategy for HCC.

Preventing future zoonosis: SARS-CoV-2 mutations enhance human-animal cross-transmission.

The COVID-19 pandemic has driven substantial evolution of the SARS-CoV-2 virus, yielding subvariants that exhibit enhanced infectiousness in humans. However, this adaptive advantage may not universally extend to zoonotic transmission. In this work, we hypothesize that viral adaptations favoring animal hosts do not necessarily correlate with increased human infectivity. In addition, we consider the potential for gain-of-function mutations that could facilitate the virus's rapid evolution in humans following adaptation in animal hosts. Specifically, we identify the SARS-CoV-2 receptor-binding domain (RBD) mutations that enhance human-animal cross-transmission. To this end, we construct a multitask deep learning model, MT-TopLap trained on multiple deep mutational scanning datasets, to accurately predict the binding free energy changes upon mutation for the RBD to ACE2 of various species, including humans, cats, bats, deer, and hamsters. By analyzing these changes, we identified key RBD mutations such as Q498H in SARS-CoV-2 and R493K in the BA.2 variant that are likely to increase the potential for human-animal cross-transmission.

Analysis of resting status reveals distinct elevational variation in metabolisms of lizards.

Animals spend a considerable proportion of their life span at rest. However, resting status has often been overlooked when investigating how species respond to environmental conditions. This may induce a large bias in understanding the local adaptation of species across environmental gradients and their vulnerability to potential environmental change. Here, we conducted an empirical study on montane agamid lizards, combined with mechanistic modeling, to compare elevational variations in body temperature and metabolisms (cumulative digestion and maintenance cost) between resting and active status. Our study on three populations of an agamid lizard along an elevational gradient revealed a trend of decreasing body temperature toward higher elevations, the main contributor of which was resting status of the lizards. Using population-specific reaction norms, we predicted greater elevational variation in hourly and cumulative digestion for resting lizards than for active lizards. Climate-change impacts, estimated as the change in cumulative digestion, also show greater elevational variation when resting status is factored into the analysis. Further, our global analysis of 98 agamid species revealed that in about half of their combined distributional range, the contribution of resting status in determining the elevational variation in cumulative digestion and maintenance cost of lizards was greater than the contribution made by a lizard's active status. Our study highlights the importance of considering resting status when investigating how species respond to environmental conditions, especially for those distributed over tropical and subtropical mountain areas.

Key role of CYP17A1 in Leydig cell function and testicular development in Qianbei Ma goats.

Reproductive traits are vital economic parameters in goat production, and boosting the reproductive capacity of breeding rams is crucial for enhancing the profitability of goat farming. Currently, research on the reproductive performance of Qianbei Ma goats mainly centers on investigating mechanisms associated with prolificacy and estrous ovulation in ewes, with limited emphasis on ram reproductive aspects. This study used scanning electron microscopy and enzyme-linked immunosorbent assay (ELISA) to profile the morphology of testis and the dynamic changes of Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), and Testosterone (T) in serum at different developmental stages of Qianbei Ma goats. Meanwhile, transcriptome sequencing technology was used to investigate the mRNA expression patterns in testicular tissues at different developmental stages: newborn (0 M), puberty (6 M), sexual maturity (12 M), and physical maturity (18 M). The results showed that the diameter, circumference, and area of the testicular seminiferous tubules gradually increased with age. The levels of T and LH in serum significantly increased from 0 to 6 months after birth (p < 0.05), followed by a stabilization of T levels and a significant decrease in LH levels (p < 0.05). Meanwhile, FSH shows a decreasing trend between 0 and 18 months after birth. A total of 26,437 differentially expressed genes were identified in 6 comparison groups, which involve various biological processes such as immunity, growth, metabolism, development, and reproduction, and are significantly enriched in signaling pathways related to testicular development and spermatogenesis. WGCNA analysis identified 6 regions significantly associated with testicular development and spermatogenesis, and selected 320 genes for constructing a PPI network. Ten candidate genes related to testicular development and spermatogenesis were identified, including TP53, PLK4, RPS9, PFN4, ACTB, CYP17A1, GPX4, CLDN1, AMH and DHH. Of these, the CYP17A1 gene promotes interstitial cell proliferation, and promotes T synthesis. This study provides a theoretical basis and data support for promoting efficient breeding of goats and early breeding of excellent male goats.

Avermectin induced vascular damage in zebrafish larvae: association with mitochondria-mediated apoptosis and VEGF/Notch signaling pathway.

Avermectin is a highly effective insecticide that has been widely used in agriculture since the 1990s. In recent years, the safety of avermectin for non-target organisms has received much attention. The vasculature is important organs in the body and participate in the composition of other organs. However, studies on the vascular safety of avermectin are lacking. The vasculature of zebrafish larvae is characterized by ease of observation and it is a commonly used model for vascular studies. Therefore, zebrafish larvae were used to explore the potential risk of avermectin on the vasculature. The results showed that avermectin induced vascular damage throughout the body of zebrafish larvae, including the head, eyes, intestine, somite, tail and other vasculature. The main forms of damage are reduction in vascular diameter, vascular area and vascular abundance. Meanwhile, avermectin induced a decrease in the number of endothelial cells and apoptosis within the vasculature. In addition, vascular damage may be related to impairment of mitochondrial function and mitochondria-mediated apoptosis. Finally, exploration of the molecular mechanisms revealed abnormal alterations in the expression of genes related to the VEGF/Notch signaling pathway. Therefore, the VEGF/Notch signaling pathway may be an important mechanism for avermectin-induced vascular damage in zebrafish larvae. This study demonstrates the vascular toxicity of avermectin in zebrafish larvae and reveals the possible molecular mechanism, which would hopefully draw more attention to the safety of avermectin in non-target organisms.

Evaluation of AlphaFold 3's Protein-Protein Complexes for Predicting Binding Free Energy Changes upon Mutation.

AlphaFold 3 (AF3), the latest version of protein structure prediction software, goes beyond its predecessors by predicting protein-protein complexes. It could revolutionize drug discovery and protein engineering, marking a major step toward comprehensive, automated protein structure prediction. However, independent validation of AF3's predictions is necessary. In this work, we evaluate AF3 complex structures using the SKEMPI 2.0 database which involves 317 protein-protein complexes and 8338 mutations. AF3 complex structures when applied to the most advanced TDL model, MT-TopLap (MultiTask-Topological Laplacian), give rise to a very good Pearson correlation coefficient of 0.86 for predicting protein-protein binding free energy changes upon mutation, which is slightly less than the 0.88 achieved earlier with the Protein Data Bank (PDB) structures. Nonetheless, AF3 complex structures led to a 8.6% increase in the prediction RMSE compared to original PDB complex structures. Additionally, some of AF3's complex structures have large errors, which were not captured in its ipTM performance metric. Finally, it is found that AF3's complex structures are not reliable for intrinsically flexible regions or domains.

Probing spin hydrodynamics on a superconducting quantum simulator.

Characterizing the nature of hydrodynamical transport properties in quantum dynamics provides valuable insights into the fundamental understanding of exotic non-equilibrium phases of matter. Experimentally simulating infinite-temperature transport on large-scale complex quantum systems is of considerable interest. Here, using a controllable and coherent superconducting quantum simulator, we experimentally realize the analog quantum circuit, which can efficiently prepare the Haar-random states, and probe spin transport at infinite temperature. We observe diffusive spin transport during the unitary evolution of the ladder-type quantum simulator with ergodic dynamics. Moreover, we explore the transport properties of the systems subjected to strong disorder or a tilted potential, revealing signatures of anomalous subdiffusion in accompany with the breakdown of thermalization. Our work demonstrates a scalable method of probing infinite-temperature spin transport on analog quantum simulators, which paves the way to study other intriguing out-of-equilibrium phenomena from the perspective of transport.

Expression of Foxtail Millet bZIP Transcription Factor SibZIP67 Enhances Drought Tolerance in Arabidopsis.

Foxtail millet is a drought-tolerant cereal and forage crop. The basic leucine zipper (bZIP) gene family plays important roles in regulating plant development and responding to stresses. However, the roles of bZIP genes in foxtail millet remain largely uninvestigated. In this study, 92 members of the bZIP transcription factors were identified in foxtail millet and clustered into ten clades. The expression levels of four SibZIP genes (SibZIP11, SibZIP12, SibZIP41, and SibZIP67) were significantly induced after PEG treatment, and SibZIP67 was chosen for further analysis. The studies showed that ectopic overexpression of SibZIP67 in Arabidopsis enhanced the plant drought tolerance. Detached leaves of SibZIP67 overexpressing plants had lower leaf water loss rates than those of wild-type plants. SibZIP67 overexpressing plants improved survival rates under drought conditions compared to wild-type plants. Additionally, overexpressing SibZIP67 in plants displayed reduced malondialdehyde (MDA) levels and enhanced activities of antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD) under drought stress. Furthermore, the drought-related genes, such as AtRD29A, AtRD22, AtNCED3, AtABF3, AtABI1, and AtABI5, were found to be regulated in SibZIP67 transgenic plants than in wild-type Arabidopsis under drought conditions. These data suggested that SibZIP67 conferred drought tolerance in transgenic Arabidopsis by regulating antioxidant enzyme activities and the expression of stress-related genes. The study reveals that SibZIP67 plays a beneficial role in drought response in plants, offering a valuable genetic resource for agricultural improvement in arid environments.