KLF11 promotes the proliferation of breast cancer cells by inhibiting p53-MDM2 signaling.

Abnormal Krüppel-like factor 11 (KLF11) expression is frequently found in tumor tissues and is associated with cancer prognosis, but its biological functions and corresponding mechanisms remain elusive. Here, we demonstrated that KLF11 functions as an oncoprotein to promote tumor proliferation in breast cancer cells. Mechanistically, at the transcription level, KLF11 decreased TP53 mRNA expression. Notably, KLF11 also interacted with and stabilized MDM2 through inhibiting MDM2 ubiquitination and subsequent degradation. This increase in MDM2 in turn accelerated the ubiquitin-mediated proteolysis of p53, leading to the reduced expression of p53 and its target genes, including CDKN1A, BAX, and NOXA1. Accordingly, data from animals further confirmed that KLF11 significantly upregulated the growth of breast cancer cells and was inversely correlated with p53 expression. Taken together, our findings reveal a novel mechanism for breast cancer progression in which the function of the tumor suppressor p53 is dramatically weakened.

A Highly Sensitive and Selective Fluorescent Sensor for Folic Acid Detection Based on D-penicillamine Stabilized Ag/Cu Alloy Nanoclusters.

In this work, a highly sensitive and selective method for detecting folic acid (FA) was developed using D-penicillamine (DPA) stabilized Ag/Cu alloy nanoclusters (DPA@Ag/Cu NCs). The yellow emission of DPA@Ag/Cu NCs was found to be quenched upon the addition of FA to the system. The fluorescence intensity quenching value demonstrated a linear relationship with FA concentrations ranging from 0.01 to 1200 µM, with a limit of detection (LOD) of 5.3 nM. Furthermore, the detection mechanism was investigated through various characterization analyses, including high resolution transmission electron microscopy, fluorescence spectra, ultraviolet-visible absorption spectra, and fluorescence lifetime. The results indicated that the fluorescence quenching induced by FA was a result of electron transfer from FA to the ligands of DPA@Ag/Cu NCs. The selectivity of the FA sensor was also evaluated, showing that common amino acids and inorganic ions had minimal impact on the detection of FA. Moreover, the standard addition method was successfully applied to detect FA in human serum, chewable tablets and FA tablets with promising results. The use of DPA@Ag/Cu NCs demonstrates significant potential for detecting FA in complex biological samples.

Mild selective photochemical oxidation of an organic sulfide using OxP-polyimide porous polymers as singlet oxygen generators.

A series of porous organic polymers based on a singlet oxygen generating oxoporphyinogen ('OxP') has been successfully prepared from a pseudotetrahedral OxP-tetraamine precursor (OxP(4-NH2Bn)4) by its reaction with tetracarboxylic acid dianhydrides under suitable conditions. Of the compounds studied, those containing naphthalene (OxP-N) and perylene (OxP-P) spacers, respectively, have large surface areas (~530 m2 g-1). On the other hand, the derivative with a simple benzene spacer (OxP-B) exhibits the best 1O2 generating capability. Although the starting OxP-tetraamine precursor is a poor 1O2 generator, its incorporation into OxP POPs leads to a significant enhancement of 1O2 productivity, which is largely due to the transformation of NH2 groups to electron-withdrawing diimides. Overall 1O2 production efficacy of OxP-POPs under irradiation by visible light is significantly improved over the common reference material PCN-222. All the materials OxP-B, OxP-N and OxP-P promote oxidation of thioanisole involving conversion of ambient triplet state oxygen to singlet oxygen under visible light irradiation and its reaction with the sulfide. Although the reaction rate of the oxidation promoted by OxP POPs is generally lower than for conventional materials (such as PCN-222) or previously studied OxP derivatives, undesired overoxidation of the substrate to methyl phenyl sulfone is suppressed. For organic sulfides, selectivity of oxidation is especially important for detoxification of mustard gas (bis(2-chloroethyl)sulfide) or similarly toxic compounds since controlled oxidation leads to the low toxicity bis(2-chloroethyl)sulfoxide while overoxidation leads to intoxification (since bis(2-chloroethyl)sulfone presents greater toxicity to humans than the sulfide substrate). Therefore, OxP POPs capable of promoting selective oxidation of sulfides to sulfoxides have excellent potential to be used as mild and selective detoxification agents.

Oxoporphyrinogen (OxP) is a unique chromophore compound in that it is intrinsically de-aggregated allowing large quantum yields of singlet oxygen generation. Due to its structure, OxP is also an ideal building block for porous systems. In this work, we describe the first incorporation of OxP in highly stable microporous polymers strongly enhanced singlet oxygen generation for selective oxidation of organic sulfides to sulfoxides (as a model reaction) under heterogeneous conditions. The novelty of this work lies in the high stability and easy recovery of the materials, the synergetic enhancement of singlet oxygen generation in the polymers over the starting OxP, and the excellent selectivity for the oxidation reaction.

Biocontrol efficiency and characterization of insecticidal protein from sugarcane endophytic Serratia marcescens (SM) against oriental armyworm Mythimna separata (Walker).

The plant endophytic bacteria are a great source of nature insecticides. However, no such endophytic bacteria have been found in sugarcane, to address this gap, we isolated and identified a strain of Serratia marcescens with moderate insecticidal activity from sugarcane. Taken armyworm Mythimna separata as example, the mortality rates of oral infection and injection infection were 47.06 % and 91 %, respectively. The SM has significant negative affect on the growth, development, and reproduction of M. separata. After determining that these insecticidal substances, 33 potential virulence proteins were screened through the identification and prediction of bacterial proteins. Later we confirmed serralysin was a vital toxic protein from SM that caused M. separata death by prokaryotic expression. In addition, we also found that the intestinal tissue cells infected with SM or serralysin were severely diseased, which may be a major factor in M. separata demise. Finally, through gene expression level, protein molecular docking, we found the aminopeptidase-N would be one of the potential receptors of serralysin. Taken together, our findings indicate that sugarcane endophyte S. marcescens may be beneficial for pest control in sugarcane and explain its insecticidal mechanism. This study provides new ideas and materials for the biological control of pests.

Photocleavable DNA Nanotube-Based Dual-Amplified Resonance Rayleigh Scattering System for MicroRNA Detection Incorporating Molecular Computing-Cascaded Keypad Lock Functionality.

Cascade molecular events in complex systems are of vital importance for enhancing molecular diagnosis and information processing. However, the conversion of a cascaded biosensing system into a multilayer encrypted molecular keypad lock remains a significant challenge in the development of molecular logic devices. In this study, we present a photocleavable DNA nanotube-based dual-amplified resonance Rayleigh scattering (RRS) system for detecting microRNA-126 (miR-126). The cascading dual-amplification biosensing system provides a multilayer-encrypted prototype with the functionality of a molecular computing cascade keypad lock. RRS signals were greatly amplified by using photocleavable DNA nanotubes and enzyme-assisted strand displacement amplification (SDA). In the presence of miR-126, enzyme-assisted SDA produced numerous identical nucleotide fragments as the target, which were then specifically attached to magnetic beads through the DNA nanotube by using a Y-shaped DNA scaffold. Upon ultraviolet irradiation, the DNA nanotube was released into the solution, resulting in an increase in the intensity of the RRS signal. This strategy demonstrated a low limit of detection (0.16 fM) and a wide dynamic range (1 fM to 1 nM) for miR-126. Impressively, the enzyme-assisted SDA offers a molecular computing model for generating the target pool, which serves as the input element for unlocking the system. By cascading the molecular computing process, we successfully constructed a molecular keypad lock with a multilevel authentication technique. The proposed system holds great potential for applications in molecular diagnosis and information security, indicating significant value in integrating molecular circuits for intelligent sensing.

Photocontrollable DNA Walker-Based Molecular Circuit for the Tunable Detection of MicroRNA-21 Using Metal-Organic Frameworks as Label-Free Fluorescence Tags.

Tunable detection of microRNA is crucial to meet the desired demand for sample species with varying concentrations in clinical settings. Herein, we present a DNA walker-based molecular circuit for the detection of miRNA-21 (miR-21) with tunable dynamic ranges and sensitivity levels ranging from fM to pM. The phosphate-activated fluorescence of UiO-66-NH2 metal-organic framework nanoparticles was used as label-free fluorescence tags due to their competitive coordination effect with the Zr atom, which significantly inhibited the ligand-to-metal charge transfer. To achieve a tunable detection performance for miR-21, the ultraviolet sensitive o-nitrobenzyl was induced as a photocleavable linker, which was inserted at various sites between the loop and the stem of the hairpin probe to regulate the DNA strand displacement reaction. The dynamic range can be precisely regulated from 700- to 67,000-fold with tunable limits of detection ranging from 2.5 fM to 36.7 pM. Impressively, a Boolean logic tree and complex molecular circuit were constructed for logic computation and cancer diagnosis in clinical blood samples. This intelligent biosensing method presents a powerful solution for converting complex biosensing systems into actionable healthcare decisions and will facilitate early disease diagnosis.

Bidirectional Relationship Between Circadian Rhythm and Frailty.

Coupled with the ageing population, frailty, characterized by high prevalence and difficult treatment, has progressively evolved into a significant public health concern. Frail individuals can often observe serious metabolic disorders and sleep-wake cycle disruption, which may be caused by the decline in physiological reserve and increased vulnerability. Moreover, sleep-wake cycle disruptions and metabolic dysfunctions associated with circadian rhythm disorders are considered to be a central part of the disorder. Previous studies have documented a correlation between frailty and sleep-wake disruptions; nevertheless, the association between circadian rhythm disorders and frailty has not yet been definitively established. Hence, we hypothesize a bidirectional link between circadian rhythm disorders and frailty, with each condition exerting a significant influence on the progression of the other's disease trajectory.

Structure-aware guided filtering for a ring artifact correction in synchrotron x-ray microtomography.

Synchrotron-based x-ray microtomography (S-µCT) is a powerful non-invasive three-dimensional (3D) imaging technique used for visualizing the internal structure of objects with micron-scale spatial resolution. However, in practical applications, ring artifacts often occur in S-µCT, which significantly degrades image quality and hinders interpretation. In this study, we propose a ring artifact correction method based on guided image filtering (GIF). The method first extracts structural prior from the input S-µCT images and then uses it as the guidance image to correct the ring artifacts. Finally, GIF with a self-guidance image is employed to further enhance image quality. Extensive comparisons and analyses on simulations and real data experiments demonstrate that the proposed method is capable of effectively correcting ring artifacts, accompanied by low-dose noise suppression and sparse-view artifact reduction. These findings suggest that the proposed method has great potential to promote the wider applications of S-µCT in the future.

The effect of chlorogenic acid, a potential botanical insecticide, on gene transcription and protein expression of carboxylesterases in the armyworm (Mythimna separata).

Chlorogenic acid (CGA) is a potential botanical insecticide metabolite that naturally occurs in various plants. Our previous studies revealed CGA is sufficient to control the armyworm Mythimna separata. In this study, we conducted a proteomic analysis of saliva collected from M. separata following exposure to CGA and found that differentially expressed proteins (DEPs) treated with CGA for 6 h and 24 h were primarily enriched in glutathione metabolism and the pentose phosphate pathway. Notably, we observed six carboxylesterase (CarE) proteins that were enriched at both time points. Additionally, these corresponding genes were expressed at levels 5.05 to 130.25 times higher in our laboratory-selected resistance strains. We also noted a significant increase in the enzyme activity of carboxylesterase following treatments with varying CGA concentrations. Finally, we confirmed that knockdown of MsCarE14, MsCarE28, and MsCCE001h decreased the susceptibility to CGA in resistance strain, indicating three CarE genes play crucial roles in CGA detoxification. This study presents the first report on the salivary proteomics of M. separata, offering valuable insights into the role of salivary proteins. Moreover, the determination of CarE mediated susceptibility change to CGA provides new targets for agricultural pest control and highlights the potential insecticide resistance mechanism for pest resistance management.

Fear of disease progression among breast cancer patients in China: a meta-analysis of studies using the fear of progression questionnaire short form.

Background: Fear of disease progression (FoP) is among the most prevalent and major psychological burdens breast cancer patients encounter. Excessive FoP may result in serious adverse effects for patients. FoP in breast cancer patients has gained attention recently; however, its prevalence in China is unknown. Objectives: This meta-analysis and systematic review aimed to assess the overall FoP among Chinese breast cancer patients to make recommendations for treatment and care. Methods: Systematic search databases included PubMed, EMbase, The Cohrane Library, Web of Science, CINAHL, PsycINFO and 4 Chinese databases (Wan Fang Data, CBM, VIP and CNKI). The retrieval time ranged from the database's establishment to March 20, 2023. After two researchers independently evaluated the literature, retrieved information, and assessed the risk of bias for the included literature, Stata 15.1 software was used to conduct a meta-analysis. Results: A total of 37 moderate or high-quality studies involving 9,689 breast cancer patients were included. Meta-analysis showed that the pooled mean score of FoP for Chinese breast cancer patients was 33.84 [95% CI (31.91, 35.77)], prediction interval (21.57 ~ 46.11). The subgroup study found that FoP levels varied among breast cancer patients of different regions, ages, educational levels, marital statuses, residences, illness stages, and disease statuses. Conclusion: Breast cancer patients have higher FoP scores. Healthcare workers should be concerned. We expect that more relevant research will be undertaken and more effective interventions will be developed. Patients can manage their illness and improve their quality of life by reducing their fears. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: PROSPERO CRD42023408914.

DNA Tile and Invading Stacking Primer-Assisted CRISPR-Cas12a Multiple Amplification System for Entropy-Driven Electrochemical Detection of MicroRNA with Tunable Sensitivity.

Conventional electrochemical detection of microRNA (miRNA) encounters issues of poor sensitivity and fixed dynamic range. Here, we report a DNA tile and invading stacking primer-assisted CRISPR-Cas12a multiple amplification strategy to construct an entropy-controlled electrochemical biosensor for the detection of miRNA with tunable sensitivity and dynamic range. To amplify the signal, a cascade amplification of the CRISPR-Cas12a system along with invading stacking primer signal amplification (ISPSA) was designed to detect trace amounts of miRNA-31 (miR-31). The target miR-31 could activate ISPSA and produce numerous DNAs, triggering the cleavage of the single-stranded linker probe (LP) that connects a methylene blue-labeled DNA tile with a DNA tetrahedron to form a Y-shaped DNA scaffold on the electrode. Based on the decrease of current, miR-31 can be accurately and efficiently detected. Impressively, by changing the loop length of the LP, it is possible to finely tune the entropic contribution while keeping the enthalpic contribution constant. This strategy has shown a tunable limit of detection for miRNA from 0.31 fM to 0.56 pM, as well as a dynamic range from ∼2200-fold to ∼270,000-fold. Moreover, it demonstrated satisfactory results in identifying cancer cells with a high expression of miR-31. Our strategy broadens the application of conventional electrochemical biosensing and provides a tunable strategy for detecting miRNAs at varying concentrations.

Incidence of delirium after non-cardiac surgery in the Chinese elderly population: a systematic review and meta-analysis.

Background: POD places a heavy burden on the healthcare system as the number of elderly people undergoing surgery is increasing annually because of the aging population. As a large country with a severely aging population, China's elderly population has reached 267 million. There has been no summary analysis of the pooled incidence of POD in the elderly Chinese population. Methods: Systematic search databases included PubMed, Web of Science, EMBASE, Cochrane Library Databases, China Knowledge Resource Integrated Database (CNKI), Chinese Biomedical Database (CBM), WanFang Database, and Chinese Science and Technology Periodicals (VIP). The retrieval time ranged from the database's establishment to February 8, 2023. The pooled incidence of delirium after non-cardiac surgery was calculated using a random effects model. Meta-regression, subgroup, and sensitivity analyses were used to explore the source of heterogeneity. Results: A total of 52 studies met the inclusion criteria, involving 18,410 participants. The pooled incidence of delirium after non-cardiac surgery in the elderly Chinese population was 18.6% (95% CI: 16.4-20.8%). The meta-regression results revealed anesthesia method and year of publication as a source of heterogeneity. In the subgroup analysis, the gender subgroup revealed a POD incidence of 19.6% (95% CI: 16.9-22.3%) in males and 18.3% (95% CI: 15.7-20.9%) in females. The year of publication subgroup analysis revealed a POD incidence of 20.3% (95% CI: 17.4-23.3%) after 2018 and 14.6 (95% CI: 11.6-17.6%) in 2018 and before. In the subgroup of surgical types, the incidence of hip fracture surgery POD was 20.7% (95% CI: 17.6-24.3%), the incidence of non-cardiac surgery POD was 18.4% (95% CI: 11.8-25.1%), the incidence of orthopedic surgery POD was 16.6% (95% CI: 11.8-21.5%), the incidence of abdominal neoplasms surgery POD was 14.3% (95% CI: 7.6-21.1%); the incidence of abdominal surgery POD was 13.9% (95% CI: 6.4-21.4%). The anesthesia methods subgroup revealed a POD incidence of 21.5% (95% CI: 17.9-25.1%) for general anesthesia, 15.0% (95% CI: 10.6-19.3%) for intraspinal anesthesia, and 8.3% (95% CI: 10.6-19.3%) for regional anesthesia. The measurement tool subgroup revealed a POD incidence of 19.3% (95% CI: 16.7-21.9%) with CAM and 16.8% (95% CI: 12.6-21.0%) with DSM. The sample size subgroup revealed a POD incidence of 19.4% (95% CI: 16.8-22.1%) for patients ≤ 500 and 15.3% (95% CI: 11.0-19.7%) for patients > 500. The sensitivity analysis suggested that the pooled incidence of postoperative delirium in this study was stable. Conclusion: Our systematic review of the incidence of delirium after non-cardiac surgery in elderly Chinese patients revealed a high incidence of postoperative delirium. Except for cardiac surgery, the incidence of postoperative delirium was higher for hip fracture surgery than for other types of surgery. However, this finding must be further explored in future large-sample studies. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: PROSPERO CRD42023397883.

d-Penicillamine@Ag/Cu Nanocluster-Based Fluorescent Nanoneuron for Logic Screening Phosphonate-Type Organophosphate Pesticides and Steganographically Encrypting Information.

Organophosphate pesticides are used in agriculture due to their high effectiveness and low persistence in eradicating insects and pests. However, conventional detection methods encounter the limitation of undesired detection specificity. Thus, screening phosphonate-type organophosphate pesticides (OOPs) from their analogues, phosphorothioate organophosphate pesticides (SOPs), remains a challenge. Here, we reported a d-penicillamine@Ag/Cu nanocluster (DPA@Ag/Cu NCs)-based fluorescence assay to screen OOPs from 21 kinds of organophosphate pesticides, which can be used for logic sensing and information encryption. Acetylthiocholine chloride was enzymatically split by acetylcholinesterase (AChE) to produce thiocholine, which reduced the fluorescence of DPA@Ag/Cu NCs due to the transmission of electrons from DPA@Ag/Cu NCs donor to the thiol group acceptor. Impressively, OOPs acted as an AChE inhibitor and retained the high fluorescence of DPA@Ag/Cu NCs due to the stronger positive electricity of the phosphorus atom. Conversely, SOPs possessed weak toxicity to AChE, which led to low fluorescence intensity. By setting 21 kinds of organophosphate pesticides as the inputs and the fluorescence of the resulting products as the outputs, DPA@Ag/Cu NCs could serve as a fluorescent nanoneuron to construct Boolean logic tree and complex logic circuit for molecular computing. As a proof of concept, by converting the selective response patterns of DPA@Ag/Cu NCs into binary strings, molecular crypto-steganography for encoding, storing, and concealing information was successfully achieved. This study is expected to advance the progress and practical application of nanoclusters in the area of logic detection and information security while also enhancing the relationship between molecular sensors and the world of information.

Benefit analysis of multi-approach biomass energy utilization toward carbon neutrality.

To reduce greenhouse gas (GHG) emissions, biomass has been increasingly developed as a renewable and clean alternative to fossil fuels because of its carbon-neutral characteristics. China has been investigating the rational development and use of bioenergy for developing its clean energy and achieving carbon neutrality. Substituting fossil fuels with multi-source and multi-approach utilized bioenergy and corresponding carbon reduction in China remain largely unexplored. Here, a comprehensive bioenergy accounting model with a multi-dimensional analysis was developed by combining spatial, life cycle, and multi-path analyses. Accordingly, the bioenergy production potential and GHG emission reduction for each distinct type of biomass feedstock through different conversion pathways were estimated. The sum of all available organic waste (21.55 EJ yr-1) and energy plants on marginal land (11.77 EJ yr-1) in China produced 23.30 EJ of bioenergy and reduced 2,535.32 Mt CO2-eq emissions, accounting for 19.48% and 25.61% of China's total energy production and carbon emissions in 2020, respectively. When focusing on the carbon emission mitigation potential of substituting bioenergy for conventional counterparts, bioelectricity was the most effective, and its potential was 4.45 and 8.58 times higher than that of gaseous and liquid fuel alternatives, respectively. In this study, life cycle emission reductions were maximized by a mix of bioenergy end uses based on biomass properties, with an optimal 78.56% bioenergy allocation from biodiesel, densified solid biofuel, biohydrogen, and biochar. The main regional bioenergy GHG mitigation focused on the Jiangsu, Sichuan, Guangxi, Henan, and Guangdong provinces, contributing to 31.32% of the total GHG mitigation potential. This study provides valuable guidance on exploiting untapped biomass resources in China to secure carbon neutrality by 2060.

Homeostasis of flavonoids and triterpenoids most likely modulates starch metabolism for pollen tube penetration in rice.

In angiosperms, the timely delivery of sperm cell nuclei by pollen tube (PT) to the ovule is vital for double fertilization. Penetration of PT into maternal stigma tissue is a critical step for sperm cell nuclei delivery, yet little is known about the process. Here, a male-specific and sporophytic mutant xt6, where PTs are able to germinate but unable to penetrate the stigma tissue, is reported in Oryza sativa. Through genetic study, the causative gene was identified as Chalcone synthase (OsCHS1), encoding the first enzyme in flavonoid biosynthesis. Indeed, flavonols were undetected in mutant pollen grains and PTs, indicating that the mutation abolished flavonoid biosynthesis. Nevertheless, the phenotype cannot be rescued by exogenous application of quercetin and kaempferol as reported in maize and petunia, suggesting a different mechanism exists in rice. Further analysis showed that loss of OsCHS1 function disrupted the homeostasis of flavonoid and triterpenoid metabolism and led to the accumulation of triterpenoid, which inhibits significantly α-amylase activity, amyloplast hydrolysis and monosaccharide content in xt6, these ultimately impaired tricarboxylic acid (TCA) cycle, reduced ATP content and lowered the turgor pressure as well. Our findings reveal a new mechanism that OsCHS1 modulates starch hydrolysis and glycometabolism through modulating the metabolic homeostasis of flavonoids and triterpenoids which affects α-amylase activity to maintain PT penetration in rice, which contributes to a better understanding of the function of CHS1 in crop fertility and breeding.

A dual-signal fluorescent colorimetric tetracyclines sensor based on multicolor carbon dots as probes and smartphone-assisted visual assay.

The widespread presence of tetracyclines in the environment has raised concerns about the potential risks to ecosystems and human health. The ratiometric fluorescence sensor for detecting tetracyclines was developed using europium-doped carbon dots (Eu-CDs) as probes under alkaline conditions. The sensing mechanism of sensor for tetracyclines was considered as inner filter effect (IFE), antenna effect (AE), and self-quenching effect (SQE). The sensor had a wide linear detection range than the reported europium ions-based tetracyclines sensors. The linear detection ranges of oxytetracycline (OTC), tetracycline (TC), doxycycline (DC) and chlorotetracycline (CTC) were respectively 0.00-603.75 µM, 0.00-623.82 µM, 0.00-594.61 µM and 0.00-601.54 µM, and the corresponding detection limits were respectively 9.50 nM, 15.80 nM, 10.40 nM and 90.30 nM. The smartphone with RGB Color Picker was further employed to analyze the concentration of tetracyclines, which provided a new method for visual tetracyclines detection. The application of Eu-CDs test paper was also explored, and the results showed that the Eu-CDs test paper has great potential application in the visual detection of tetracyclines. In addition, the accuracy of the established tetracyclines sensor was compared with that of the China national standard method by high-performance liquid chromatography (HPLC), and the results showed that the established method in this work has similar accuracy to the China national standard method. The sensor has been employed to detect tetracyclines in the actual samples with satisfactory results, which indicated that this method has promising applications in the real-time monitoring tetracyclines of food and environment.

Morphological Risk Factors for Posterior Cruciate Ligament Tear and Tibial Avulsion Injuries of the Tibial Plateau and Femoral Condyle.

BACKGROUND: Identification of morphological risk factors associated with the knee that threaten ligaments is important for understanding injury mechanisms and prevention. However, the morphological risk factors for posterior cruciate ligament (PCL) lesions are not clearly understood. PURPOSE: To investigate whether the medial tibial depth (MTD), medial and lateral posterior tibial slope, asymmetry of the medial and lateral slopes, radius of the sagittal plane medial femoral condyle, coronal tibial slope, and notch width index (NWI) were risk factors for PCL intrasubstance tearing (PCLIT) and tibial avulsion fractures (PCLAF). STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Between January 2015 and March 2022, 82 patients with isolated PCLIT, 68 patients with isolated PCLAF, and 82 controls without any ligamentous or meniscal pathologic findings as determined via physical examination and magnetic resonance imaging were included. Values were compared among the 3 groups. Logistic regression analysis was performed to confirm the risk factors. Receiver operating characteristic curves were defined for the morphological indicators and combination of risk factors. RESULTS: Logistic regression analysis revealed (1) MTD, lateral minus medial posterior tibial slope, radius of the posterior circle of the medial femoral condyle, and NWI as significant independent predictors for PCLIT and (2) MTD and NWI for PCLAF. The areas under the curve combining the 4 indicators for PCLIT and noncontact PCLIT were 0.79 (95% CI, 0.72-0.86) and 0.90 (95% CI, 0.85-0.96), respectively. The area under the curve for the combination of MTD and NWI for PCLAF was 0.78 (95% CI, 0.70-0.86). CONCLUSION: Decreased MTD and NWI were associated with an increased incidence of PCLIT and PCLAF. Increased asymmetry of the medial and lateral slopes and the radius of the posterior circle of the medial femoral condyle were associated with the presence of PCLIT. In addition, the model of a combination of risk factors showed good predictive ability for noncontact PCLIT. These findings may aid clinicians in identifying patients at risk for PCL lesions. Further studies are warranted for identifying the effect of these factors on biomechanical mechanisms.

Metabolic and Nonmetabolic Functions of PSAT1 Coordinate Signaling Cascades to Confer EGFR Inhibitor Resistance and Drive Progression in Lung Adenocarcinoma.

Emerging evidence demonstrates that the dysregulated metabolic enzymes can accelerate tumorigenesis and progression via both metabolic and nonmetabolic functions. Further elucidation of the role of metabolic enzymes in EGFR inhibitor resistance and metastasis, two of the leading causes of death in lung adenocarcinoma, could help improve patient outcomes. Here, we found that aberrant upregulation of phosphoserine aminotransferase 1 (PSAT1) confers erlotinib resistance and tumor metastasis in lung adenocarcinoma. Depletion of PSAT1 restored sensitivity to erlotinib and synergistically augmented the tumoricidal effect. Mechanistically, inhibition of PSAT1 activated the ROS-dependent JNK/c-Jun pathway to induce cell apoptosis. In addition, PSAT1 interacted with IQGAP1, subsequently activating STAT3-mediated cell migration independent of its metabolic activity. Clinical analyses showed that PSAT1 expression positively correlated with the progression of human lung adenocarcinoma. Collectively, these findings reveal the multifunctionality of PSAT1 in promoting tumor malignancy through its metabolic and nonmetabolic activities. SIGNIFICANCE: Metabolic and nonmetabolic functions of PSAT1 confer EGFR inhibitor resistance and promote metastasis in lung adenocarcinoma, suggesting therapeutic targeting of PSAT1 may attenuate the malignant features of lung cancer.

The insecticidal effect of the botanical insecticide chlorogenic acid on Mythimna separata (Walker) is related to changes in MsCYP450 gene expression.

The oriental armyworm Mythimna separata (Walker) (Lepidoptera: Noctuidae) can feed on the leaves of many crops, resulting in vast areas of damage and severe losses. Therefore, this insect has become a significant agricultural pest in north Asia. In this study, we fed 3rd instar larvae with artificial diets containing different concentrations of chlorogenic acid and found a significant lethal effect and the mortality increased with increasing chlorogenic acid concentration. Next, we measured the sublethal effect of chlorogenic acid at LC20 on the growth and development of M. separata larvae. The durations of the 4th and 5th instar were longer than those of the control group (prolonged by 0.8 and 0.6 days, respectively), and the 6th instar was shorter (by 1.1 days). The total survival rate, pupation rate, eclosion rate, sex ratio, and oviposition amount in the LC20 chlorogenic acid-treated group were significantly lower than those in the control group. Furthermore, transcriptome analysis of 3rd instar larvae fed various concentrations of chlorogenic acid revealed that several MsCYP450 genes were significantly up-regulated, and this finding was further validated by qRT-PCR. In addition, various concentrations of chlorogenic acid and different treatment times significantly affected the enzyme activity of CYP450 in 3rd instar larvae. Importantly, dietary ingestion of dsMsCYP450 significantly reduced the mRNA level of MsCYP450 genes and increased mortality in the presence of chlorogenic acid. Our results revealed that MsCYP6B6, MsCYP321A7, and MsCYP6B7-like play an essential role in the detoxification of chlorogenic acid by M. separata. This study provides evidence of control effect by botanical insecticide chlorogenic acid on M. separata, and potential detoxification mechanism mediated by P450 of botanical insecticide in arthropods.