The PKA-CREB1 axis regulates coronavirus proliferation by viral helicase nsp13 association.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a worldwide threat in the past 3 years. Although it has been widely and intensively investigated, the mechanism underlying the coronavirus-host interaction requires further elucidation, which may contribute to the development of new antiviral strategies. Here, we demonstrated that the host cAMP-responsive element-binding protein (CREB1) interacts with the non-structural protein 13 (nsp13) of SARS-CoV-2, a conserved helicase for coronavirus replication, both in cells and in lung tissues subjected to SARS-CoV-2 infection. The ATPase and helicase activity of viral nsp13 were shown to be potentiated by CREB1 association, as well as by Protein kinase A (PKA)-mediated CREB1 activation. SARS-CoV-2 replication is significantly suppressed by PKA Cα, cAMP-activated protein kinase catalytic subunit alpha (PRKACA), and CREB1 knockdown or inhibition. Consistently, the CREB1 inhibitor 666-15 has shown significant antiviral effects against both the WIV04 strain and the Omicron strain of the SARS-CoV-2. Our findings indicate that the PKA-CREB1 signaling axis may serve as a novel therapeutic target against coronavirus infection. IMPORTANCE: In this study, we provide solid evidence that host transcription factor cAMP-responsive element-binding protein (CREB1) interacts directly with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) helicase non-structural protein 13 (nsp13) and potentiate its ATPase and helicase activity. And by live SARS-CoV-2 virus infection, the inhibition of CREB1 dramatically impairs SARS-CoV-2 replication in vivo. Notably, the IC50 of CREB1 inhibitor 666-15 is comparable to that of remdesivir. These results may extend to all highly pathogenic coronaviruses due to the conserved nsp13 sequences in the virus.

Comprehensive analysis of environmental exposure to hazardous trace elements and lung function: a national cross-sectional study.

BACKGROUND: There is growing interest in the joint effects of hazardous trace elements (HTEs) on lung function deficits, but the data are limited. This is a critical research gap given increased global industrialisation. METHODS: A national cross-sectional study including spirometry was performed among 2112 adults across 11 provinces in China between 2020 and 2021. A total of 27 HTEs were quantified from urine samples. Generalised linear models and quantile-based g-computation were used to explore the individual and joint effects of urinary HTEs on lung function, respectively. RESULTS: Overall, there were negative associations between forced expiratory volume in 1 s (FEV1) and urinary arsenic (As) (z-score coefficient, -0.150; 95% CI, -0.262 to -0.038 per 1 ln-unit increase), barium (Ba) (-0.148, 95% CI: -0.258 to -0.039), cadmium (Cd) (-0.132, 95% CI: -0.236 to -0.028), thallium (Tl) (-0.137, 95% CI: -0.257 to -0.018), strontium (Sr) (-0.147, 95% CI: -0.273 to -0.022) and lead (Pb) (-0.121, 95% CI: -0.219 to -0.023). Similar results were observed for forced vital capacity (FVC) with urinary As, Ba and Pb and FEV1/FVC with titanium (Ti), As, Sr, Cd, Tl and Pb. We found borderline associations between the ln-quartile of joint HTEs and decreased FEV1 (-20 mL, 95% CI: -48 to +8) and FVC (-14 mL, 95% CI: -49 to+2). Ba and Ti were assigned the largest negative weights for FEV1 and FVC within the model, respectively. CONCLUSION: Our study investigating a wide range of HTEs in a highly polluted setting suggests that higher urinary HTE concentrations are associated with lower lung function, especially for emerging Ti and Ba, which need to be monitored or regulated to improve lung health.

Effects of a co-bacterial agent on the growth, disease control, and quality of ginseng based on rhizosphere microbial diversity.

BACKGROUND: The ginseng endophyte Paenibacillus polymyxa Pp-7250 (Pp-7250) has multifaceted roles such as preventing ginseng diseases, promoting growth, increasing ginsenoside accumulation, and degrading pesticide residues, however, these effects still have room for improvements. Composite fungicides are an effective means to improve the biocontrol effect of fungicides, but the effect of Pp-7250 in combination with its symbiotic bacteria on ginseng needs to be further investigated, and its mechanism of action has not been elucidated. In this study, a series of experiments was conducted to elucidate the effect of Paenibacillus polymyxa and Bacillus cereus co-bacterial agent on the yield and quality of understory ginseng, and to investigate their mechanism of action. RESULTS: The results indicated that P. polymyxa and B. cereus co-bacterial agent (PB) treatment improved ginseng yield, ginsenoside accumulation, disease prevention, and pesticide degradation. The mechanism is that PB treatment increased the abundance of beneficial microorganisms, including Rhodanobacter, Pseudolabrys, Gemmatimonas, Bacillus, Paenibacillus, Cortinarius, Russula, Paecilomyces, and Trechispora, and decreased the abundance of pathogenic microorganisms, including Ellin6067, Acidibacter, Fusarium, Tetracladium, Alternaria, and Ilyonectria in ginseng rhizosphere soil. PB co-bacterial agents enhanced the function of microbial metabolic pathways, biosynthesis of secondary metabolites, biosynthesis of antibiotics, biosynthesis of amino acids, carbon fixation pathways in prokaryotes, DNA replication, and terpenoid backbone biosynthesis, and decreased the function of microbial plant pathogens and animal pathogens. CONCLUSION: The combination of P. polymyxa and B. cereus may be a potential biocontrol agent to promote the resistance of ginseng to disease and improve the yield, quality, and pesticide degradation.

Key Role of Vegetation Cover in Alleviating Microplastic-Enhanced Carbon Emissions.

Microplastics (MPs) are considered to influence fundamental biogeochemical processes, but the effects of plant residue-MP interactions on soil carbon turnover in urban greenspaces are virtually unknown. Here, an 84-day incubation experiment was constructed using four types of single-vegetation-covered soils (6 years), showing that polystyrene MP (PSMP) pollution caused an unexpectedly large increase in soil CO2 emissions. The additional CO2 originating from highly bioavailable active dissolved organic matter molecules (<380 °C, predominantly polysaccharides) was converted from persistent carbon (380-650 °C, predominantly aromatic compounds) rather than PSMP derivatives. However, the priming effect of PSMP derivatives was weakened in plant-driven soils (resistivity: shrub > tree > grass). This can be explained from two perspectives: (1) Plant residue-driven humification processes reduced the percentage of bioavailable active dissolved organic matter derived from the priming effects of PSMPs. (2) Plant residues accelerated bacterial community succession (dominated by plant residue types) but slowed fungal community demise (retained carbon turnover-related functional taxa), enabling specific enrichment of glycolysis, the citric acid cycle and the pentose phosphate pathway. These results provide a necessary theoretical basis to understand the role of plant residues in reducing PSMP harm at the ecological level and refresh knowledge about the importance of biodiversity for ecosystem stability.

A Nanoconfined FeCo2O4-Embedded Ceramic Membrane Regulates Electron Transfer in Peroxymonosulfate Activation to Selectively Generate Singlet Oxygen for Water Decontamination.

Peroxymonosulfate (PMS)-based advanced oxidation processes (AOPs), as a promising technology for water decontamination, are constrained by low reaction kinetics due to limited reaction selectivity and mass transfer. Herein, we designed a nanoconfined FeCo2O4-embedded ceramic membrane (FeCo2O4-CM) under flow-through pattern for PMS activation. Confining PMS and FeCo2O4 within nanochannels (3.0-4.7 nm) enhanced adsorption interactions (-7.84 eV vs -2.20 eV), thus boosting mass transfer. Nanoconfinement effect regulated electron transfer pathways from PMS to FeCo2O4-CM by modulating the active site transformation to ≡Co(III) in nanoconfined FeCo2O4-CM, enabling selectively generating 1O2. The primary role of 1O2 in the nanoconfined system was confirmed by kinetic solvent isotope experiments and indicative anthracene endoperoxide (DPAO2). The system enabled 100% removal of atrazine (ATZ) within a hydraulic retention time of 2.124 ms, demonstrating a rate constant over 5 orders of magnitude higher than the nonconfined system (3.50 × 103 s-1 vs 0.42 min-1). It also exhibited strong resilience to pH variations (3.3-9.0) and coexisting substances, demonstrating excellent stability indicated by consistent 100% ATZ removal for 14 days. This study sheds light on regulating electron transfer pathways to selectively generate 1O2 through the nanoconfinement effect, boosting the practical application of PMS-based AOPs in environmental remediation and potentially applying them to various other AOPs.

Environmental remediation and sustainable design of iron oxide nanoparticles for removal of petroleum-derived pollutants from water: A critical review.

The global problem of major oil spills not only generates crude oil pollution, but produces many derivatives that pose ecological and human health challenges. While extensive research has focused on understanding the types of these contaminants, their transport modes, detection techniques, and ecotoxicological impacts, there are still significant research gaps in mechanisms for removal of petroleum-derived pollutants by iron oxide nanoparticles (IONPs). This work summarizes systematically the types and green synthesis of IONPs for the environmental remediation of various petroleum contaminants. We also provide comprehensive coverage of the excellent removal capacity and latest environmental remediation of IONPs-based materials (e.g., pristine, modified, or porous-supported IONPs materials) for the removal of petroleum-derived pollutants, potential interaction mechanisms (e.g., adsorption, photocatalytic oxidation, and synergistic biodegradation). A sustainable framework was highlighted in depth based on a careful assessment of the environmental impacts, associated hazards, and economic viability. Finally, the review provides an possible improvements of IONPs for petroleum-derived pollutants remediation and sustainable design on future prospect. In the current global environment of pollution reduction and carbon reduction, this information is very important for researchers to synthesize and screen suitable IONPs for the control and eradication of future petroleum-based pollutants with low environmental impact.

Photoaged polystyrene microplastics result in neurotoxicity associated with neurotransmission and neurodevelopment in zebrafish larvae (Danio rerio).

Microplastics (MPs) are emerging pollutants widely distributed in the environment, inducing toxic effects in various organisms. However, the neurotoxicity and underlying mechanisms of simulated sunlight-aged MPs have rarely been investigated. In this study, zebrafish (Danio rerio) were exposed to environmentally relevant concentrations (0, 0.1, 1, 10, and 100 µg/L) of virgin polystyrene (V-PS) and aged polystyrene (A-PS) for 120 hpf to evaluate the neurotoxicity. The results demonstrated that simulated sunlight irradiation altered the physicochemical properties (morphology, functional groups, and chemical composition) of V-PS. Exposure to A-PS causes greater toxicity on locomotor ability in larval zebrafish than V-PS. Motor neuron development was disrupted by transgenic (hb9-GFP) zebrafish larvae exposed to A-PS, with significant alterations in neurotransmitter levels (ACh, DA, 5-HT, and GABA) and enzyme activity (AChE, ChAT, and ChE). Further investigation found that exposure to A-PS had a significantly impact on the expression of neurotransmission and neurodevelopment-related genes in zebrafish. These findings suggest that A-PS induces neurotoxicity by its effects on neurotransmission and neurodevelopment. This study highlights the neurotoxic effects and mechanisms of simulated sunlight irradiation of MPs, providing new insights for assessing the ecological risks of photoaged MPs in the environment.

Rerouting phytosterol degradation pathway for directed androst-1,4-diene-3,17-dione microbial bioconversion.

Steroid-based drugs are now mainly produced by the microbial transformation of phytosterol, and a two-step bioprocess is adopted to reach high space-time yields, but byproducts are frequently observed during the bioprocessing. In this study, the catabolic switch between the C19- and C22-steroidal subpathways was investigated in resting cells of Mycobacterium neoaurum NRRL B-3805, and a dose-dependent transcriptional response toward the induction of phytosterol with increased concentrations was found in the putative node enzymes including ChoM2, KstD1, OpccR, Sal, and Hsd4A. Aldolase Sal presented a dominant role in the C22 steroidal side-chain cleavage, and the byproduct was eliminated after sequential deletion of opccR and sal. Meanwhile, the molar yield of androst-1,4-diene-3,17-dione (ADD) was increased from 59.4 to 71.3%. With the regard of insufficient activity of rate-limiting enzymes may also cause byproduct accumulation, a chromosomal integration platform for target gene overexpression was established supported by a strong promoter L2 combined with site-specific recombination in the engineered cell. Rate-limiting steps of ADD bioconversion were further characterized and overcome. Overexpression of the kstD1 gene further strengthened the bioconversion from AD to ADD. After subsequential optimization of the bioconversion system, the directed biotransformation route was developed and allowed up to 82.0% molar yield with a space-time yield of 4.22 g·L-1·day-1. The catabolic diversion elements and the genetic overexpression tools as confirmed and developed in present study offer new ideas of M. neoaurum cell factory development for directed biotransformation for C19- and C22-steroidal drug intermediates from phytosterol. KEY POINTS: • Resting cells exhibited a catabolic switch between the C19- and C22-steroidal subpathways. • The C22-steroidal byproduct was eliminated after sequential deletion of opccR and sal. • Rate-limiting steps were overcome by promoter engineering and chromosomal integration.

Clinical features, disease progression, and nuclear imaging in ATXN2-related parkinsonism in a longitudinal cohort.

BACKGROUND: Spinocerebellar ataxia 2 (SCA2) with a low range of CAG repeat expansion of ATXN2 gene can present with predominant or isolated parkinsonism that closely resembles Parkinson's disease (PD). This study is aimed at comparing clinical features, disease progression, and nuclear imaging between ATXN2-related parkinsonism (ATXN2-P) and PD. METHODS: Three hundred and seventy-seven clinically diagnosed PD with family history were screened by multiplex ligation-dependent probe amplification, whole-exome sequencing or target sequencing, and dynamic mutation testing of 10 SCA subtypes. The baseline and longitudinal clinical features as well as the dual-tracer positron emission tomography (PET) imaging were compared between ATXN2-P and genetically undefined familial PD (GU-fPD). RESULTS: Fifteen ATXN2-P patients from 7 families and 50 randomly selected GU-fPD patients were evaluated. Significantly less resting tremor and more symmetric signs were observed in ATXN2-P than GU-fPD. No significant difference was found in motor progression and duration from onset to occurrence of fluctuation, dyskinesia, and recurrent falls between the two groups. Cognitive impairment and rapid-eye-movement sleep behavior disorder were more common in ATXN2-P. During follow-up, olfaction was relatively spared, and no obvious progression of cognition dysfunction evaluated by Mini-Mental State Examination scores was found in ATXN2-P. PET results of ATXN2-P demonstrated a symmetric, diffuse, and homogenous dopamine transporter loss of bilateral striatum and a glucose metabolism pattern inconsistent with that in PD. CONCLUSIONS: Symmetric motor signs and unique nuclear imaging might be the clues to distinguish ATXN2-P from GU-fPD.

Unraveling the link between childhood maltreatment and depression: Insights from the role of ventral striatum and middle cingulate cortex in hedonic experience and emotion regulation.

Childhood maltreatment is an established risk factor for psychopathology. However, it remains unclear how childhood traumatic events relate to mental health problems and how the brain is involved. This study examined the serial mediation effect of brain morphological alterations and emotion-/reward-related functions on linking the relationship from maltreatment to depression. We recruited 156 healthy adolescents and young adults and an additional sample of 31 adolescents with major depressive disorder for assessment of childhood maltreatment, depressive symptoms, cognitive reappraisal and anticipatory/consummatory pleasure. Structural MRI data were acquired to identify maltreatment-related cortical and subcortical morphological differences. The mediation models suggested that emotional maltreatment of abuse and neglect, was respectively associated with increased gray matter volume in the ventral striatum and greater thickness in the middle cingulate cortex. These structural alterations were further related to reduced anticipatory pleasure and disrupted cognitive reappraisal, which contributed to more severe depressive symptoms among healthy individuals. The above mediating effects were not replicated in our clinical group partly due to the small sample size. Preventative interventions can target emotional and reward systems to foster resilience and reduce the likelihood of future psychiatric disorders among individuals with a history of maltreatment.

Intraoperative cell salvage reduces postoperative allogeneic blood transfusion and shortens off-bed time in simultaneous bilateral total hip arthroplasty: a single-center retrospective study.

BACKGROUND: Simultaneous bilateral total hip arthroplasty (SI-THA) results in more blood loss and a greater need for postoperative allogeneic blood transfusion (ABT). Previous studies have reported that multimodal patient blood management (PBM) strategies were associated with a smaller effect of intraoperative cell salvage (ICS) in unilateral total hip arthroplasty. However, there are few studies on the role of ICS in SI-THA. This study aims to explore the effect of ICS with multimodal PBM strategies on SI-THA and to identify risk factors associated with ABT. METHODS: This retrospective matched cohort study included 72 patients in the ICS group and 72 patients in the control group who were matched according to age, sex, and year of hospitalization. Demographic data, hematological indicators, blood loss, and ABT were compared between the two groups. Logistic regression analysis was performed to identify independent risk factors for postoperative ABT. Postoperative outcomes were also recorded. RESULTS: In the cohort of 144 patients, 27 patients (37.5%) in the ICS group while 45 patients (62.5%) in the control group received postoperative ABT after SI-THA. Compared with the control group, the ICS group showed significant differences in terms of blood loss, postoperative hemoglobin and hematocrit. The transfused volume of allogeneic red blood cells per ABT patient was also lower in the ICS group. Multivariate logistic regression analysis indicated that sex, the utilization of ICS, and preoperative hematocrit level were identified as independent factors associated with postoperative ABT. The utilization of ICS significantly shortened off-bed time and length of hospital stay, but had no effect on early pain and functional outcomes. CONCLUSION: The utilization of ICS can significantly affect postoperative ABT in SI-THA patients with multimodal PBM strategies. Sex, the utilization of ICS and preoperative hematocrit level were identified as independent factors associated with postoperative ABT. The utilization of ICS promoted weight-bearing functional exercises, but had no effect on early outcomes.

Effect of lower limb alignment on outcome after lateral unicompartmental knee arthroplasty: a retrospective study.

PURPOSE: The objective of this study was to investigate the correlation between lower limb alignment and patient outcomes after lateral unicompartmental knee arthroplasty (LUKA). METHODS: In this retrospective study, the information of 51 patients who underwent lateral UKA was collected after an average of 27months of follow-up (13 to 60 months). Evaluation indicators include the AKS and WOMAC score. The Kellgren-Lawrence grade is used to evaluate the severity of osteoarthritis, while the hip-knee-ankle (HKA) angle is utilized to measure the valgus angle of lower limb alignment. RESULT: Patients with postoperative valgus (≥ 3°) alignment had the best outcomes, while those with varus (≤-3°) alignment had the worst outcomes (p < 0.001). Furthermore, it was noted that patients with preoperative mild valgus (≤ 4°) alignment had worse postoperative outcomes than those with severe valgus (≥ 7°) alignment (p < 0.05). The study also revealed a positive correlation between postoperative valgus and WOMAC scores (p < 0.001), whereas a negative correlation was observed between the change in valgus angle and WOMAC scores (p = 0.005). CONCLUSION: During follow-ups, we found that lower limb alignment seems to be an independent predictor of postoperative outcomes. It is recommended that more than 3° of valgus alignment should be maintained after LUKA. Surgeons performing lateral UKA should be cautious of overcorrecting alignment, particularly in patients with preoperative mild valgus alignment.

Unicompartmental knee arthroplasty combined with posterior cruciate ligament reconstruction: a case report.

BACKGROUND: In this study, we present the unique case of a patient with knee osteoarthritis (OA) of the medial compartment and posterior cruciate ligament (PCL) deficiency who underwent simultaneous medial unicompartmental knee arthroplasty (UKA) and PCL reconstruction. CASE PRESENTATION: A 49-year-old male patient presented with a 1-year history of pain and instability in the left knee. The patient had previously experienced a trauma-related injury to the PCL of the left knee that was left untreated. Imaging and physical examination confirmed the presence of left medial knee OA along with PCL rupture. To address these issues, the patient underwent UKA combined with PCL reconstruction. The patient's Lysholm score was 47 before surgery and 81 three months after surgery, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was 29 before surgery and 18 three months after surgery, and the International Knee Documentation Committee (IKDC) subjective score was 56.3 before surgery and 74.7 three months after surgery. Six months after surgery, the patient's gait returned to normal, and he was able to jog. CONCLUSION: This case report presents the first instance of UKA combined with PCL reconstruction and introduces a novel treatment approach for patients suffering from medial knee OA and ligament injury.

Human molybdenum exposure risk in industrial regions of China: New critical effect indicators and reference dose.

Evidence increasingly suggests molybdenum exposure at environmental levels is still associated with adverse human health, emphasizing the necessity to establish a more protective reference dose (RfD). Herein, we conducted a study measuring 15 urinary metals and 30 clinical health indicators in 2267 participants residing near chemical enterprises across 11 Chinese provinces to investigate their relationships. The kidney and cystatin-C emerged as the most sensitive organ and critical effect indicator of molybdenum exposure, respectively. Odds of cystatin-C-defined chronic kidney disease (CKD) in the highest quantile of molybdenum exposure significantly increased by 133.5% (odds ratio [OR]: 2.34, 95% CI: 1.78, 3.11) and 75.8% (OR: 1.76, 95% CI: 1.24, 2.49) before and after adjusting for urinary 14 metals, respectively. Intriguingly, cystatin-C significantly mediated 15.9-89.5% of molybdenum's impacts on liver and lung function, suggesting nephrotoxicity from molybdenum exposure may trigger hepatotoxicity and pulmonary toxicity. We derived a new RfD for molybdenum exposure (0.87 µg/kg-day) based on cystatin-C-defined estimated glomerular filtration rate by employing Bayesian Benchmark Dose modeling analysis. This RfD is significantly lower than current exposure guidance values (5-30 µg/kg-day). Remarkably, >90% of participants exceeded the new RfD, underscoring the significant health impacts of environmental molybdenum exposure on populations in industrial regions of China.

Surgical treatment for recurrent patellar dislocation with severe torsional deformities: Double-level derotational osteotomy may not have a clear advantage over single-level derotational osteotomy in improving clinical and radiological outcomes.

PURPOSE: The purpose of this study was to investigate whether double-level (femur + tibia) derotational osteotomy is superior to single-level femoral derotational osteotomy for recurrent patellar dislocation with severe femoral and tibial rotational deformities (femoral anteversion >30° and external tibial torsion >30°). METHODS: Between January 2015 and June 2020, a total of 115 knees with recurrent patellar dislocation treated with combined medial patellofemoral ligament reconstruction (MPFL-R) and derotational osteotomies were evaluated after a minimum follow-up of 2 years. Among these cases, 15 knees that underwent double-level derotational osteotomy were included in the double-level group, which was propensity-matched in a 1:2 ratio to a single-level group of patients who underwent single-level femoral derotational osteotomy (30 knees). The clinical and radiological outcomes were evaluated and compared between the groups. Furthermore, the foot progression angle was measured preoperatively and 2 years after surgery. RESULTS: The patient-specific variables did not differ significantly between the double- and the single-level groups after propensity score matching. The postoperative mean foot progression angle was significantly lower in the double-level group than in the single-level group (9° ± 8° vs. 15° ± 11°; p = 0.014); however, there were no statistically significant differences between the groups in terms of any other clinical and radiological assessments. CONCLUSION: For patients with severe femoral and tibial torsional deformities (femoral anteversion >30° and external tibial torsion >30°), the double-level derotational osteotomy is superior to single-level osteotomy in maintaining normal foot progression angle, but it does not show an advantage in terms of patient-reported outcomes, radiological results and redislocation rate at minimum 2 years of follow-up. Furthermore, concomitant excessive external tibial torsion (>30°) did not have an adverse effect on clinical outcomes in patients who underwent derotational distal femoral osteotomy with MPFL-R due to excessive femoral anteversion. LEVEL OF EVIDENCE: Level III.

Habitual patellar dislocation exhibits less severe rotational deformities but poorer trochlear development and higher incidence of patella baja compared with recurrent patellar dislocation in skeletally mature patients.

PURPOSE: This study compared the radiological characteristics between habitual and recurrent patellar dislocation in skeletally mature patients. METHODS: From 2017 to 2019, 77 skeletally mature patients with habitual patellar dislocation were surgically treated at a single institution and reviewed retrospectively. A total of 55 knees from these patients were included in the habitual patellar dislocation group. During the same period, 55 knees with recurrent patellar dislocation were randomly selected from 242 patients and included in the recurrent patellar dislocation group. Various bony deformities were measured and compared between the two groups. Additionally, a subgroup analysis was conducted among patients with habitual patellar dislocation, comparing those with and without an 'invisible patella' observed on true lateral views with 30° of knee flexion. RESULTS: The femoral anteversion angle (21.8° vs. 26.3°, p = 0.041), tibiofemoral rotation angle (9.7° vs. 12.4°, p = 0.042) and external tibial rotation angle (24.3° vs. 29.6°, p = 0.001) in the habitual patellar dislocation group were significantly lower than those in the recurrent patellar dislocation group. 54% of knees in the habitual patellar dislocation group had a patella baja, and this was in sharp contrast to the recurrent patellar dislocation group in which none of the knees had a patella baja. 49.1% of knees in the habitual patellar dislocation group showed 'invisible patella' at 30° of knee flexion, and knees with 'invisible patella' had significantly higher tibial tubercle-trochlear groove (TT-TG) distance (30.4 vs. 19.8, p < 0.001) and tibiofemoral rotation angle (13.2° vs. 6.4°, p < 0.001) than knees with a visible patella. CONCLUSIONS: A distinct difference in bony anatomical features was observed between habitual and recurrent patellar dislocation in skeletally mature patients. Habitual patellar dislocation exhibited less severe rotational deformities of the lower extremity but showed poorer trochlear and patellar development, a larger TT-TG distance and a higher incidence of patella baja compared with recurrent patellar dislocation. LEVEL OF EVIDENCE: Level III.

Derotational distal femoral osteotomy improves subjective function and patellar tracking after medial patellofemoral ligament reconstruction in recurrent patellar dislocation patients with increased femoral anteversion: A systematic review and meta-analysis.

PURPOSE: The purpose of this study is to systematically review and quantitatively analyse the clinical outcomes of combined derotational distal femoral osteotomy (D-DFO) and medial patellofemoral ligament reconstruction (MPFL-R) in the treatment of recurrent patellar dislocation (RPD) with increased femoral anteversion angle (FAA). METHODS: This study was performed in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the Methodological Quality Of Systematic Reviews) Guidelines. PubMed, Embase, Web of Science and Cochrane Library databases were searched to identify studies reporting clinical outcomes of combined D-DFO and MPFL-R in RPD patients with increased FAA. Data on patient-reported outcome measures, radiological parameters, patellar tracking as revealed by J-sign and complications were extracted based on the inclusion criteria. The Methodological Index for Non-Randomized Study score was used for quality assessment. Review Manager and R statistical software were used to perform the statistical analysis. RESULTS: Eleven studies with a total of 569 knees in 553 patients were included. Patients were predominantly female (79%). The weighted mean of FAA decreased from 33.6° to 13.0° (weighted mean difference = 20.59; p < 0.00001) after the combined procedure. Significant improvements (p < 0.00001) were identified in the Lysholm score (weighted mean: 55.5 vs. 80.4), International Knee Documentation Committee (IKDC) score (weighted mean: 52.8 vs. 78.6) and Kujala score (weighted mean: 54.5 vs. 80.6). The incidence of residual J-sign ranged from 14.3% to 38.3% with an overall pooled rate of 28.2% (95% confidence interval = 22.8%-33.6%). The overall redislocation rate was 1.1%. No patients experienced surgical site infection or bone nonunion. Two studies compared the clinical outcomes of MPFL-R with and without D-DFO. Compared with isolated MPFL-R, the combined procedure yielded a better Lysholm score (weighted mean: 84.9 vs. 79.3, p < 0.0001), IKDC score (weighted mean: 84.1 vs. 79.9, p = 0.001), Kujala score (weighted mean: 84.3 vs. 79.4, p < 0.0001) and a lower residual J-sign rate (26/97 [26.8%] vs. 44/105 [41.9%], p = 0.02), respectively. CONCLUSION: The combination of D-DFO and MPFL-R led to improved clinical outcomes and a low redislocation rate in patients with RPD and increased FAA. Additional D-DFO can achieve more favourable results in subjective function and patellar tracking than isolated MPFL-R in the setting of excessive FAA. LEVEL OF EVIDENCE: Level IV.

Recurrent patellar dislocation patients with high-grade J-sign have multiple structural bone abnormalities in the lower limbs.

PURPOSE: To explore the relationship between preoperative J-sign grading and structural bone abnormalities in patients with recurrent patellar dislocation (RPD). METHODS: A retrospective study was conducted on RPD patients over 5 years. Patients were categorised based on J-sign grade into low (J- and J1+), moderate (J2+) and high groups (J3+). Trochlear dysplasia (TD) and osseous structures (femoral anteversion angle [FAA], knee torsion, tibial tuberosity-trochlear groove [TT-TG] distance, Caton-Deschamps index) were assessed and grouped according to risk factor thresholds. The χ2 test was used to compare composition ratio differences of structural bone abnormalities among the groups. RESULTS: A total of 256 patients were included, with 206 (80.5%) females. The distribution of J-sign grade was as follows: 89 knees (34.8%) of low grade, 86 moderate (33.6%) and 81 high (31.6%). Among the five structural bone abnormalities, TD was the most common with a prevalence of 78.5%, followed by increased TT-TG at 47.4%. Excessive tibiofemoral rotation had the lowest occurrence at 28.9%. There were 173 (67.6%) patients who had two or more abnormalities, while 45 (17.6%) had four to five bony abnormalities. Among patients with any bony abnormality, the proportion of high-grade J-sign surpassed 40%. Patients with moderate and high-grade J-sign had more increased FAA and more pronounced patella alta (all p < 0.001). The proportion of excessive knee torsion and TD increased with increasing each J-sign grade, with the more notable tendency in knee torsion (high vs. moderate vs. low-grade: 61% vs. 22% vs 7%, p < 0.001). Furthermore, the higher J-sign grade was also associated with more combined bony abnormalities (p < 0.001). In the high-grade J-sign group, 90.2% of the knees had two or more bony risk factors and 40.7% had four or more, which were significantly higher than the moderate and low-grade J-sign groups (40.7% vs. 11.6% vs. 2.2%, p < 0.001). CONCLUSION: In patients with a high-grade J-sign, over 90% of the lower limbs had two or more structural bone risk factors, and more than 40% had four or more. These proportions were significantly higher compared to knees with low-grade and moderate J-sign. In clinical practice, when treating high-grade patellar mal-tracking, it is important to focus on and correct these strongly correlated abnormal bone structures. LEVEL OF EVIDENCE: Level III.

Galactic Cosmic Ray Particle Exposure Does Not Increase Protein Levels of Inflammation or Oxidative Stress Markers in Rat Microglial Cells In Vitro.

Astronauts on exploratory missions will be exposed to galactic cosmic rays (GCR), which can induce neuroinflammation and oxidative stress (OS) and may increase the risk of neurodegenerative disease. As key regulators of inflammation and OS in the CNS, microglial cells may be involved in GCR-induced deficits, and therefore could be a target for neuroprotection. This study assessed the effects of exposure to helium (4He) and iron (56Fe) particles on inflammation and OS in microglia in vitro, to establish a model for testing countermeasure efficacy. Rat microglia were exposed to a single dose of 20 cGy (300 MeV/n) 4He or 2 Gy 56Fe (600 MeV/n), while the control cells were not exposed (0 cGy). Immediately following irradiation, fresh media was applied to the cells, and biomarkers of inflammation (cyclooxygenase-2 [COX-2], nitric oxide synthase [iNOS], phosphorylated IκB-α [pIκB-α], tumor necrosis factor-α [TNFα], and nitrite [NO2-]) and OS (NADPH oxidase [NOX2]) were assessed 24 h later using standard immunochemical techniques. Results showed that radiation did not increase levels of NO2- or protein levels of COX-2, iNOS, pIκB-α, TNFα, or NOX2 compared to non-irradiated control conditions in microglial cells (p > 0.05). Therefore, microglia in isolation may not be the primary cause of neuroinflammation and OS following exposures to helium or iron GCR particles.

Using unsupervised learning to classify inlet water for more stable design of water reuse in industrial parks.

The water reuse facilities of industrial parks face the challenge of managing a growing variety of wastewater sources as their inlet water. Typically, this clustering outcome is designed by engineers with extensive expertise. This paper presents an innovative application of unsupervised learning methods to classify inlet water in Chinese water reuse stations, aiming to reduce reliance on engineer experience. The concept of 'water quality distance' was incorporated into three unsupervised learning clustering algorithms (K-means, DBSCAN, and AGNES), which were validated through six case studies. Of the six cases, three were employed to illustrate the feasibility of the unsupervised learning clustering algorithm. The results indicated that the clustering algorithm exhibited greater stability and excellence compared to both artificial clustering and ChatGPT-based clustering. The remaining three cases were utilized to showcase the reliability of the three clustering algorithms. The findings revealed that the AGNES algorithm demonstrated superior potential application ability. The average purity in six cases of K-means, DBSCAN, and AGNES were 0.947, 0.852, and 0.955, respectively.