The eEF1A protein in cancer: Clinical significance, oncogenic mechanisms, and targeted therapeutic strategies.

Eukaryotic elongation factor 1A (eEF1A) is among the most abundant proteins in eukaryotic cells. Evolutionarily conserved across species, eEF1A is in charge of translation elongation for protein biosynthesis as well as a plethora of non-translational moonlighting functions for cellular homeostasis. In malignant cells, however, eEF1A becomes a pleiotropic driver of cancer progression via a broad diversity of pathways, which are not limited to hyperactive translational output. In the past decades, mounting studies have demonstrated the causal link between eEF1A and carcinogenesis, gaining deeper insights into its multifaceted mechanisms and corroborating its value as a prognostic marker in various cancers. On the other hand, an increasing number of natural and synthetic compounds were discovered as anticancer eEF1A-targeting inhibitors. Among them, plitidepsin was approved for the treatment of multiple myeloma whereas metarrestin was currently under clinical development. Despite significant achievements in these two interrelated fields, hitherto there lacks a systematic examination of the eEF1A protein in the context of cancer research. Therefore, the present work aims to delineate its clinical implications, molecular oncogenic mechanisms, and targeted therapeutic strategies as reflected in the ever expanding body of literature, so as to deepen mechanistic understanding of eEF1A-involved tumorigenesis and inspire the development of eEF1A-targeted chemotherapeutics and biologics.

Two cases of driver death caused by airbag rupture.

OBJECTIVE: This article reports two accidents caused by defective Takata airbags ruptured, which led to the deaths of the drivers. This is the first public report on the deaths caused by Takata airbags in China. METHODS: Determine the relationship between the driver death and airbag rupture through autopsy indings and vehicle inspection. RESULTS: Due to defects in the design of Takata's inflator, moist air was permitted to slowly enter the inflator, resulting the PSAN slowly degraded physically. The damaged propellant burned more rapidly than intended and overpressurized the inflator's steel housing, causing fragmentation and flying debris at high speed, killing or injuring vehicle occupants. CONCLUSIONS: To date, there are still tens of millions of defective Takata airbags that have not been recalled for repair, posing safety risks. This article suggests taking preventive measures to avoid the occurrence of similar accidents.

Discovery of a nitroaromatic nannocystin with potent in vivo anticancer activity against colorectal cancer by targeting AKT1.

The development of targeted chemotherapeutic agents against colorectal cancer (CRC), one of the most common cancers with a high mortality rate, is in a constant need. Nannocystins are a family of myxobacterial secondary metabolites featuring a 21-membered depsipeptide ring. The in vitro anti-CRC activity of natural and synthetic nannocystins was well documented, but little is known about their in vivo efficacy and if positive, the underlying mechanism of action. In this study we synthesized a nitroaromatic nannocystin through improved preparation of a key fragment, and characterized its in vitro activity and in vivo efficacy against CRC. We first described the total synthesis of compounds 2-4 featuring Heck macrocyclization to forge their 21-membered macrocycle. In a panel of 7 cancer cell lines from different tissues, compound 4 inhibited the cell viability with IC values of 1-6 nM. In particular, compound 4 (1, 2, 4 nM) inhibited the proliferation of CRC cell lines (HCT8, HCT116 and LoVo) in both concentration and time dependent manners. Furthermore, compound 4 concentration-dependently inhibited the colony formation and migration of CRC cell lines. Moreover, compound 4 induced cell cycle arrest at sub-G1 phase, apoptosis and cellular senescence in CRC cell lines. In three patient-derived CRC organoids, compound 4 inhibited the PDO with IC values of 3.68, 28.93 and 11.81 nM, respectively. In a patient-derived xenograft mouse model, injection of compound 4 (4, 8 mg/kg, i.p.) every other day for 12 times dose-dependently inhibited the tumor growth without significant change in body weight. We conducted RNA-sequencing, molecular docking and cellular thermal shift assay to elucidate the anti-CRC mechanisms of compound 4, and revealed that it exerted its anti-CRC effect at least in part by targeting AKT1.

Polystyrene microplastics enhance oxidative dissolution but suppress the aquatic acute toxicity of a commercial cadmium yellow pigment under simulated irradiation.

Commercial cadmium yellow (CdS) pigment widely coexist with microplastics (MPs) in surface water, thus it is important to understand how MPs affect CdS pigment stability and toxicity under irradiation. Herein, the dissolution of CdS pigment (krelease = 0.118 h-1) under irradiation was visibly increased to 0.144 h-1 by polystyrene (PS) MPs, due to reactive species generation such as 1O2, •OH and 3PS* , while O2•- was unimportant to this process. The O2, humic acid, photoaging status of PS MPs could promote PS MPs-related CdS pigment dissolution rate by modifying reactive species generation. However, the CO32-, PO43- and alkaline condition significantly decreased the dissolution rate to 0.091, 0.053 and 0.094 h-1, respectively, through modifying free Cd2+ stability. Comparably, PS MPs-related CdS pigment dissolution was relatively slow in natural water samples (krelease = 0.075 h-1). PS MPs at environmental concentration can also promote CdS pigment dissolution and Cd2+ release, but suppress acute toxicity of CdS pigment to zebrafish larvae as increasing 10 h survival from 65% to 85% by adsorbing the Cd2+ and decreasing Cd2+ bioavailability. This study emphasized the environmental risks and human safety of CdS pigment should be carefully evaluated in the presence of PS MPs in aquatic environments.

[Surgical technique of lateral unicompartmental knee arthroplasty and discussion of the maximum correction value in the treatment of knee valgus deformity].

Objective: To investigate the surgical technique and the short-term effectivenss of lateral unicompartmental knee arthroplasty (LUKA) through lateral approach in the treatment of valgus knee and to calculate the maximum value of the theoretical correction of knee valgus deformity. Methods: A retrospective analysis was performed on 16 patients (20 knees) who underwent LUKA and met the selection criteria between April 2021 and July 2022. There were 2 males and 14 females, aged 57-85 years (mean, 71.5 years). The disease duration ranged from 1 to 18 years, with an average of 11.9 years. Knee valgus was staged according to Ranawat classification, there were 6 knees of type Ⅰ, 13 knees of type Ⅱ, and 1 knee of type Ⅲ. All patients were assigned the expected correction value of genu valgus deformity by preoperative planning, including the correction value of lateral approach, intra-articular correction value, and residual knee valgus deformity value. The actual postoperative corrected values of the above indicators were recorded and the theoretical maximum correctable knee valgus deformity values were extrapolated. The operation time, intraoperative blood loss, incision length, hospital stay, hip-knee-ankle angle (HKA), mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibia angle (mMPTA), joint line convergence angle (JLCA), posterior tibial slope (PTS), range of motion (ROM), Hospital for Special Surgery (HSS) score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score were also recorded for effectiveness evaluation. Results: The patients' incision length averaged 13.83 cm, operation time averaged 85.8 minutes, intraoperative blood loss averaged 74.9 mL, and hospital stay averaged 6.7 days. None of the patients suffered any significant intraoperative neurological or vascular injuries. All patients were followed up 10-27 months, with a mean of 17.9 months. One patient with bilateral knee valgus deformities had intra-articular infection in the left knee at 1 month after operation and the remaining patients had no complication such as prosthesis loosening, dislocation, and infection. The ROM, HSS score, and WOMAC score of knee joint significantly improved at each time point after operation when compared to those before operation, and the indicators further improved with time after operation, the differences were all significant ( P<0.05). Imaging measurement showed that HKA, mLDFA, JLCA, and PTS significantly improved at 3 days after operation ( P<0.05) except for mMPTA ( P>0.05). Postoperative evaluation of the knee valgus deformity correction values showed that the actual intra-articular correction values ranged from 0.54° to 10.97°, with a mean of 3.84°. The postoperative residual knee valgus deformity values ranged from 0.42° to 5.30°, with a mean of 3.59°. The actual correction values of lateral approach ranged from 0.21° to 12.73°, with a mean of 4.26°. Conclusion: LUKA through lateral approach for knee valgus deformity can achieve good early effectiveness. Preoperative planning can help surgeons rationally allocate the correction value of knee valgus deformity, provide corresponding treatment strategies, and the maximum theoretical correction value of knee valgus deformity can reach 25°.

Digestive perianastomotic ulcerations after intestinal resection in children.

Digestive perianastomotic ulceration (DPAU) is a rare complication after intestinal resection and anastomosis occurring at or near the anastomosis site. The purpose of this review is to summarize the characteristics of DPAU, including the etiology, diagnosis and differential diagnosis, clinical manifestations, treatment, and future research. All recent literature on DPAU was searched in PubMed, Embase, and Cochrane and then reviewed. The clinical manifestations of DPAU are mainly gastrointestinal symptoms such as bloody stool and chronic anemia. The diagnosis of DPAU is difficult. Specific diseases, such as Crohn's disease, must be ruled out before a diagnosis can be made. In addition, there are no clear treatment guidelines due to the high degree of heterogeneity in response to drugs and surgery. It is recommended to adjust medication in time and combine various treatment methods. In addition, the mechanism that causes DPAU is not well understood; however, several possible mechanisms have been proposed, such as scar tissue ischemia and underlying diseases. Moreover, there is a high risk of relapses, and a long-term follow-up is necessary. Numerous issues remain to be solved in this area; therefore, more randomized controlled trials and studies should be carried out to further understand this disease.

Prevalence and genetic diversity of multidrug-resistant Salmonella Typhimurium monophasic variant in a swine farm from China.

Salmonella 4,[5],12:i:-, a monophasic variant of S. Typhimurium, has become a global serovar causing animal and human infections since its first emergence in the late 1980's. Several previous studies showed the increasing prevalence of S. 4,[5],12:i:- in China, most of which were from swine with multidrug resistance (MDR) profiles. However, the molecular characteristic and evolution of S. 4,[5],12:i:- in the same swine farm are still unknown. In this study, a total of 54 S. enterica strains were isolated from different fattening pigs aged 1, 3, and 6 months, most of which belonged to S. 4,[5],12:i:-. Whole-genome sequencing revealed that all 45 S. 4,[5],12:i:- strains belonged to ST34 and were further divided into two different ribosomal STs and nine different core-genome STs. Phylogenetic analysis of 286 S. 4,[5],12:i:- strains in China, including 241 from the EnteroBase Salmonella database, revealed the genetic diversity of S. 4,[5],12:i:- and indicated that S. 4,[5],12:i:- in this swine farm might have multiple origins. Three different IncHI2 plasmids carrying various resistance genes were characterized by nanopore sequencing and could be conjugated to Escherichia coli. The colistin resistance gene mcr-1 and ESBLs gene blaCTX - M-14 were co-located on the chromosome of one strain. The dynamic changes in antimicrobial resistance regions and transferability of IncHI2 plasmids, as well as the chromosomal location of resistance genes, facilitated the diversity of the antimicrobial resistance characteristics in S. 4,[5],12:i:-. Since the swine farm is regarded as the important reservoir of MDR S. 4,[5],12:i:-, the prevalence and evolution of S. 4,[5],12:i:- from swine farms to pig products and humans should be continually monitored.

Heck Macrocyclization in Forging Non-Natural Large Rings including Macrocyclic Drugs.

The intramolecular Heck reaction is a well-established strategy for natural product total synthesis. When constructing large rings, this reaction is also referred to as Heck macrocyclization, which has proved a viable avenue to access diverse naturally occurring macrocycles. Less noticed but likewise valuable, it has created novel macrocycles of non-natural origin that neither serve as nor derive from natural products. This review presents a systematic account of the title reaction in forging this non-natural subset of large rings, thereby addressing a topic rarely covered in the literature. Walking through two complementary sections, namely (1) drug discovery research and (2) synthetic methodology development, it demonstrates that beyond the well-known domain of natural product synthesis, Heck macrocyclization also plays a remarkable role in forming synthetic macrocycles, in particular macrocyclic drugs.

Anticancer Small-Molecule Agents Targeting Eukaryotic Elongation Factor 1A: State of the Art.

Eukaryotic elongation factor 1A (eEF1A) canonically delivers amino acyl tRNA to the ribosomal A site during the elongation stage of protein biosynthesis. Yet paradoxically, the oncogenic nature of this instrumental protein has long been recognized. Consistently, eEF1A has proven to be targeted by a wide assortment of small molecules with excellent anticancer activity, among which plitidepsin has been granted approval for the treatment of multiple myeloma. Meanwhile, metarrestin is currently under clinical development for metastatic cancers. Bearing these exciting advances in mind, it would be desirable to present a systematic up-to-date account of the title topic, which, to the best of our knowledge, has thus far been unavailable in the literature. The present review summarizes recent advances in eEF1A-targeting anticancer agents, both naturally occurring and synthetically crafted, with regard to their discovery or design, target identification, structure-activity relationship, and mode of action. Their structural diversity and differential eEF1A-targeting mechanisms warrant continuing research in pursuit of curing eEF1A-driven malignancy.

Site-directed late-stage diversification of macrocyclic nannocystins facilitating anticancer SAR and mode of action studies.

Nannocystins are a family of 21-membered cyclodepsipeptides with excellent anticancer activity. However, their macrocyclic architecture poses a significant challenge to structure modification. Herein, this issue is addressed by leveraging the strategy of post-macrocyclization diversification. In particular, a novel serine-incorporating nannocystin was designed so that its appending hydroxyl group could diversify into a wide variety of side chain analogues. Such effort facilitated not only structure-activity correlation at the subdomain of interest, but also the development of a macrocyclic coumarin-labeled fluorescence probe. Uptake experiments indicated good cell permeability of the probe, and endoplasmic reticulum was identified as its subcellular localization site.

Mid-Term Outcomes of Navigation-Assisted Primary Total Knee Arthroplasty Using Adjusted Mechanical Alignment.

OBJECTIVE: The adjusted mechanical alignment (aMA) technique is an extension of conventional mechanical alignment (MA), which has rarely been reported. The purpose of this study was to evaluate mid-term outcomes of navigation-assisted total knee arthroplasty (TKA) using aMA. METHODS: This retrospective cohort study enrolled 63 consecutive patients (77 knees) who underwent navigation-assisted TKA using aMA between September 2017 and October 2019. Fifty-two consecutive patients (61 knees) who underwent TKA using MA during the same period were assessed as the controlled group. The demographic data and perioperative data were recorded. The parameters of resection and soft tissue balance including tibia resection angle, frontal femoral angle, axial femoral angle, joint line translation, medial and lateral gap in extension and flexion position were recorded. Radiographic parameters and functional scores including the Hospital for Special Surgery (HSS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and Forgotten Joint Score-12 (FJS-12) were evaluated. Surgery-related complications were recorded. The average follow-up was 3.5 years, with a minimum of 2.4 years. RESULTS: The frontal femoral angle was 2.55° ± 1.08° in aMA group versus 0.26° ± 0.60° in MA group (p < 0.001). The axial femoral angle was 3.07° ± 2.23° external in aMA group versus 2.30° ± 1.70° in MA group (p = 0.027). The lateral flexion gap was wider in the aMA group, with a mean of 0.71 mm more laxity (p = 0.001). Postoperative coronal alignment was 177.03° ± 1.82° in aMA group versus 178.14° ± 1.69° in MA group (p < 0.001). The coronal femoral component angle was 92.62° ± 2.78° in aMA group versus 90.85° ± 2.01° in MA group (p < 0.001). Both aMA-TKA and MA-TKA achieved satisfactory mid-term clinical outcomes. However, the HSS scores at 1 month postoperatively were significantly higher using aMA than using MA (p < 0.001). CONCLUSION: Navigation-assisted TKA using aMA technique obtained satisfactory mid-term clinical outcomes. The aMA technique aims to produce a biomimetic wider lateral flexion-extension gap and minimize releases of soft tissues, which might be associated with better early clinical outcomes than MA technique.

Polystyrene microplastics reduce Cr(VI) and decrease its aquatic toxicity under simulated sunlight.

Microplastics (MPs) serve as vectors for chromium (Cr), influencing its fate and toxicity in aquatic environments, and have attracted much attention recently. However, it is still unknown whether MPs mediate Cr species transformation under sunlight irradiation. This study confirmed that polystyrene (PS) MPs could reduce Cr(VI) to Cr(III) under sunlight irradiation, with a photoreduction rate constant of 0.0023 h-1. PS MPs-mediated Cr(VI) reduction was predominantly dependent on O2•- and simultaneously suppressed by 1O2, •OH and 3PS* . Aged PS MPs were exposed to simulated sunlight irradiation for 0, 200, 500, and 800 h, and Cr(VI) reduction was hindered by increased 1O2 and •OH formation and light-screening effects (decreased photon absorption). The size, functional groups and concentration of PS MPs and environmental factors (e.g., humic acid, pH, Mg2+, Fe3+ and O2) strongly affected Cr(VI) reduction. Furthermore, Cr(VI) reduction induced by PS MPs could occur in reservoir water, and the reduction rate was faster than that in double distilled (DD) water. Correspondingly, PS MPs (1 mg/L) decreased the oxidative stress induced by Cr(VI) to Lemna minor in reservoir water after 96 h of sunlight irradiation. This study provided deep insight into how PS MPs affect Cr species transformations and hazardous effects in realistic aquatic environments under sunlight conditions.

Polystyrene microplastics protect lettuce (Lactuca sativa) from the hazardous effects of Cu(OH)2 nanopesticides.

Copper-based nanopesticides are released into the environment during foliar spray application, and they could, on their own or in combination with microplastics (MPs), pose threats to environmental safety and human health. In this study, Cu(OH)2 nanowires greatly decreased the vigor of lettuce seeds (p< 0.01) and the root length of lettuce seedlings (p< 0.01) and significantly altered the lettuce antioxidant defence system and MDA content (p< 0.05). Released Cu2+ played a critical role in the toxicity mechanism of Cu(OH)2 nanowires in lettuce seedlings, as evidenced by the substantial accumulation of Cu in the seedling roots (p< 0.01) rather than in the leaves. Polystyrene (PS) MPs (1 mg/L) stimulated lettuce seedling growth, as shown by the (highly) significant increase in root and leaf length and in the seed vigor index (p< 0.01 or 0.05). Notably, PS MPs (1 mg/L) neutralized the hazardous effects of 1 mg/L Cu(OH)2 nanowire treatment on lettuce growth, as reflected by the vitality and root length of the seedlings returning to normal levels. The PS MPs (1 mg/L) absorbed on middle root surfaces and strongly hindered Cu accumulation in lettuce roots, which was the predominant mechanism by which PS MPs suppressed the hazardous effects of the Cu(OH)2 nanowires. This study strengthens the understanding of the toxicity and toxicity mechanisms of Cu(OH)2 nanowires with or without PS MPs in the environment.

Biomechanical and Finite-Element Analysis of Femoral Pin-Site Fractures Following Navigation-Assisted Total Knee Arthroplasty.

BACKGROUND: Femoral pin-site fracture is one of the most serious complications of navigation-assisted total knee arthroplasty (TKA). Its occurrence is associated with the loss of biomechanical strength caused by intraoperative femoral drilling. This study aimed to investigate the drilling location as a risk factor for pin-site fracture. METHODS: A biomechanical analysis using rabbit femora was performed to determine the effects of drilling eccentricity and height. Torsional, 3-point bending, and axial compression tests were performed to evaluate biomechanical parameters, including failure strength, failure displacement, and stiffness. Fracture type and the presence of comminution were noted and analyzed. Finite-element analysis (FEA) was utilized to assess the stress distribution and deformation. The cumulative sum (CUSUM) method was applied to define the safe range for drilling eccentricity. RESULTS: Drilling operations were accurately implemented. Biomechanical tests confirmed that severely eccentric drilling significantly reduced the biomechanical strength of the femur, especially in torsion. FEA results provided evidence of threatening stress concentration in severely eccentric drilling. The overall safe range of eccentricity relative to the center of the femur was found to be between 50% of the radius in the anterolateral direction and 70% of the radius in the posteromedial direction. CONCLUSIONS: Severely eccentric drilling significantly increased the risk of femoral pin-site fracture, especially under torsional stress. Femoral drilling should be performed in the safe zone that was identified.

Anti-inflammatory Study on the Constituents of Angelica sinensis (Oliv.) Diels, Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav., Angelica pubescence Maxim and Foeniculum vulgare Mill. Essential Oils.

Umbelliferae plants, which are widely used as traditional Chinese medicine because of their characteristics of relieving rheumatism, alleviating fever, circulating blood and easing pain. This experimental study was based on ear edema model caused by 12-O-tetracycline-propylphenol-13-acetic acid (TPA) in mice and compared with the Ibuprofen (Ib) group. Gas chromatography-mass spectrometry (GC-MS) was used to analyse the composition of the essential oils from the four studied Umbelliferae plants (Angelica sinensis (Oliv.) Diels, A. dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav., A. pubescens Maxim and Foeniculum vulgare Mill.). Biologically active components in volatile oils from the four studied Umbelliferae plants were evaluated. The expression levels of inflammatory cytokines Tumor Necrosis Factor-α (TNF-α), Cyclooxygenase-2 (COX-2), Interleukin-6 (IL-6) and RelA (p65) in mouse skin were determined by immunohistochemical method. The refractive index of the four essential oils was calculated. A total of 239 compounds were identified by GC-MS from the four studied plants, and the main constituents were osthole (44.61%, APEOs), obepin (0.59%, APEOs & 86.58%, FVEOs), undecanol (8.58%, ADEOs), α-muurolene (7.95%, ADEOs) and cis-anethol (9.11%, ADEOs). E-ligustilide (0.14%, APEOs & 81.14%, ASEOs), (-)-spathulenol (0.08%, FVEOs & 1.21%, ASEOs), (-)-terpinen-4-ol (4.91%, FVEOs), 2-butylthiolane (5.76%, APEOs) and α-bisabolol (3.80%, APEOs). This study showed that all the essential oils from the four studied Umbelliferae plants contained various lactones, including ligustrongolactone, trans-anisol and imperatorin. According to the results of the TPA induction test in the mouse ear edema model, the essential oils of four Umbelliferae plants reduced the levels of inflammatory cytokines TNF-α, COX-2, IL-6 and p65. All of them showed extraordinary biological activity in anti-inflammatory, so they have potential application value for biomedical products, pharmaceutical preparations, natural functional nutrients and cosmetic additives.

Aromatic-turmerone ameliorates DSS-induced ulcerative colitis via modulating gut microbiota in mice.

Curcuma longa L. is one of the traditional Chinese herbs in the list of medicinal and food homology. Aromatic-turmerone is the main ingredient in turmeric essential oil. The aim of the present study is to investigate the treatment of Aromatic-turmerone on DSS-included colitis and its regulatory effect on intestinal flora disorder. Male KM mice supplemented with different concentration of aromatic-turmerone and mesalazine are subjected to 2% DSS in drinking water to induce colitis. Colon and cecum contents were collected for colitis lesion evaluation and inflammation-related gene analysis and colon contents for gut microbiota. The results show that treatments with Aromatic-turmerone significantly prevents colon shortening, alleviates the damage of colonic tissue, and reduces colonic inflammatory cytokines TNF-α and COX-2. Furthermore, the 16S rDNA gene sequence data indicate that Aromatic-turmerone improve the abundance of bacterial species, maintain some beneficial bacteria, and reduce harmful bacteria. Aromatic-turmerone downregulates the colonic inflammatory cytokines and modulates the abundance of intestinal flora, which is conductive to ameliorates DSS-induced colitis. Regularly intake of the edible herb may be help to prevent ulcerative colitis-related diseases.

Total Knee Arthroplasty Using Adjusted Restricted Kinematic Alignment for the Treatment of Severe Varus Deformity: Technical Note.

OBJECTIVE: To describe a new alignment technique of adjusted restricted kinematic alignment (arKA) for the treatment of severe varus deformity in total knee arthroplasty. METHODS: Three female patients (three severe varus knees) who underwent navigation-assisted total knee arthroplasty (TKA) using arKA from April 2020 to September 2020 were included in this study, with an average age of 71.33 years (range, 61 to 80 years). General anesthesia was given to all patients. Intraoperative observations including tibia resection angle, frontal femoral angle, axial femoral angle, medial and lateral gap in the extension and flexion positions and joint line translation were recorded. Also, operation duration and drainage volume were recorded. Radiographic parameters including the mechanical axis (α), coronal femoral component angle (ß), coronal tibial component angle (γ), sagittal femoral component angle (δ), tibial posterior slope angle (ε), femoral-patella angle (θ), and femoral notching were assessed. Clinical evaluation was performed using the Hospital for Special Surgery (HSS) Score and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Score. Both individual and mean measurement data were displayed. RESULTS: The mean tibial resection was 4.00° varus (range, 3° to 5°), and the mean frontal femoral angle was 3.67° varus (range, 3° to 4°) in extension. The flexion lateral gap was wider than the medial gap with a mean laxity of 1.34 mm. Moreover, the mean axial femoral angle was 2.67° external (range, 0° to 6°) in flexion, and the mean joint line translation was 1.00 mm proximal (range, 0 to 3 mm). In addition, the mean preoperative mechanical axis was 156.22° (range, 153.65° to 158.90°) and the mean postoperative mechanical axis was 174.04° (range, 173.83° to 174.17°) with a mean correction of 17.82°. The mean femoral angle was 92.60° (range, 91.29° to 93.30°) and the mean tibial angle was 86.95° (range, 86.83° to 87.04°) in coronal plane. The HSS score improved from an average of 46.67 points (range, 42 to 51) preoperatively to 83.67 points (range, 81 to 86) at 3 months postoperatively. The mean WOMAC score was 16.33 points at 3 months postoperatively. CONCLUSIONS: The new alignment technique of arKA aims to balance the flexion and extension gap without extensive releases of soft tissue and restore the native pre-arthritic alignment, may be a promising alignment strategy for treating severe varus deformity. However, further study and comparison with other alignment techniques is needed.

Chemical constituents, biological activities and anti-rheumatoid arthritic properties of four citrus essential oils.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease with predominant synovitis that has no complete cure or preventive treatment. Citrus essential oils, used in natural fragrances, contain a variety of functional ingredients that are worthy of investigation for their potential as natural anti-inflammatory drug sources. In this study, essential oils were hydro distilled from the peels of four citrus species: Citrus sinensis (L.) Osbeck (CSEOs), Citrus paradisi Macfad. (CPEOs), Citrus limon (L.) Osbeck (CLEOs) and Citri Reticulatae Pericarpium (CREOs). Altogether, 81 compounds were identified using gas chromatography-mass spectrometry (GC-MS), of which d-limonene (17.96%-94.66%) was an abundant component of all four oils. The stable 1,1-diphenyl-2-pyrrole hydrazine (DPPH) free radical test showed that all four essential oils had excellent antioxidant properties (IC50 , 0.76-13.86 µg/mL). Furthermore, the oils remarkably increased the first G1 phase of the cell cycle, which inhibited the pro-inflammatory factor expression. An immunohistochemical analysis indicated that the four essential oils inhibited the expression of tumor necrosis factor-α and cyclooxygenase-2 and they exhibited anti-inflammatory activity in a rat model that was similar to that of the common drug, Ibuprofen. These results show that the CSEOs, CPEOs, CLEOs, and CREOs have significant antirheumatic activities and thus have great potential in developing functional food or drugs for treating RA.

Polystyrene microplastics sunlight-induce oxidative dissolution, chemical transformation and toxicity enhancement of silver nanoparticles.

The coexistence of microplastics (MPs) and nanomaterials has been increasingly studied, but the influence of MPs on the chemical transformation of nanomaterials remains unclear. Herein, it was demonstrated that polystyrene (PS) MPs induce the oxidative dissolution, transformation and toxicity of silver nanoparticles (Ag NPs) under simulated sunlight irradiation. The PS MPs induced the oxidation dissolution of pristine Ag NPs by 1O2, OH and/or acid release and simultaneously reduced the released Ag+ to secondary Ag NPs by O2-. The sizes, functional groups and ageing status of the PS MPs and pH characterized secondary Ag NPs formation. Secondary formation of Ag NPs induced by PS MPs also occurred in realistic water and was governed by dissolved organic matter (DOM) and Cl-, rather than SO42- or CO32-. Moreover, PS MPs remarkably promoted Ag+ release, altered the Ag+:Ag0 ratio, and presented vehicle effects on Ag+ toxicity to Daphnia magna. The concentration addition model demonstrated that the ion-related toxicity of Ag NPs was significantly increased by PS MPs. Therefore, PS MPs induced the oxidative dissolution, transformation and toxicity enhancement of Ag NPs under sunlight irradiation, and accordingly, the coexistence of PS MPs and Ag NPs in freshwater environments should be seriously considered.

Zinc oxide nanoparticles dissolution and toxicity enhancement by polystyrene microplastics under sunlight irradiation.

Zinc oxide nanoparticles (ZnO NPs) dissolution is a critical process for the transformation and toxicity of ZnO NPs in aquatic environments. However, the effect of microplastics (MPs) on dissolution and toxicity of ZnO NPs under sunlight irradiation is still lacking. Herein, the dramatic increase in sunlight-induced ZnO NPs dissolution by polystyrene (PS) MPs was proven, which was attributed to the increase in h+-dependent and proton-dependent ZnO NPs dissolution by PS MPs, yielding 1O2 generation inhibition and acid release, respectively. The sizes, functional groups and aging status of PS MPs and pH were characteristic ZnO NPs dissolution through modifying 1O2, •OH and O2•- generation and acid release. Furthermore, the ZnO NPs dissolution affected by PS MPs also occurred in three realistic water samples, which were mainly governed by dissolved organic matter (DOM) and CO32-, rather than Cl- or SO42-. The PS MPs (1 µg/mL) dramatically altered the Zn2+:ZnO ratio in ZnO NPs suspension after 96 h of sunlight irradiation and presented vehicle effects on Zn2+, which in turn significantly increased the ion-related toxicity of ZnO NPs to Daphnia magna. Based on the PS MPs enhanced dissolution and toxicity of ZnO NPs, the effects of PS MPs on the environmental risk assessment of ZnO NPs should be seriously considered in freshwater environments under sunlight irradiation.