Three consecutive cytosolic glycolysis enzymes modulate autophagic flux.

Autophagy serves as an important recycling route for the growth and survival of eukaryotic organisms in nutrient-deficient conditions. Since starvation induces massive changes in the metabolic flux that are coordinated by key metabolic enzymes, specific processing steps of autophagy may be linked with metabolic flux-monitoring enzymes. We attempted to identify carbon metabolic genes that modulate autophagy using VIGS screening of 45 glycolysis- and Calvin-Benson cycle-related genes in Arabidopsis (Arabidopsis thaliana). Here, we report that three consecutive triose-phosphate-processing enzymes involved in cytosolic glycolysis, triose-phosphate-isomerase (TPI), glyceraldehyde-3-phosphate dehydrogenase (GAPC), and phosphoglycerate kinase (PGK), designated TGP, negatively regulate autophagy. Depletion of TGP enzymes causes spontaneous autophagy induction and increases AUTOPHAGY-RELATED 1 (ATG1) kinase activity. TGP enzymes interact with ATG101, a regulatory component of the ATG1 kinase complex. Spontaneous autophagy induction and abnormal growth under insufficient sugar in TGP mutants are suppressed by crossing with the atg101 mutant. Considering that triose-phosphates are photosynthates transported to the cytosol from active chloroplasts, the TGP enzymes would be strategically positioned to monitor the flow of photosynthetic sugars and modulate autophagy accordingly. Collectively, these results suggest that TGP enzymes negatively control autophagy acting upstream of the ATG1 complex, which is critical for seedling development.

Stress-responsive Gdf15 counteracts renointestinal toxicity via autophagic and microbiota reprogramming.

The integrated stress response (ISR) plays a pivotal role in the cellular stress response, primarily through global translational arrest and the upregulation of cellular adaptation-linked molecules. Growth differentiation factor 15 (Gdf15) is a potent stress-responsive biomarker of clinical inflammatory and metabolic distress in various types of diseases. Herein, we assess whether ISR-driven cellular stress contributes to pathophysiological outcomes by modulating Gdf15. Clinical transcriptome analysis demonstrates that PKR is positively associated with Gdf15 expression in patients with renal injury. Gdf15 expression is dependent on protein kinase R (PKR)-linked ISR during acute renointestinal distress in mice and genetic ablation of Gdf15 aggravates chemical-induced lesions in renal tissues and the gut barrier. An in-depth evaluation of the gut microbiota indicates that Gdf15 is associated with the abundance of mucin metabolism-linked bacteria and their enzymes. Moreover, stress-responsive Gdf15 facilitates mucin production and cellular survival via the reorganization of the autophagy regulatory network. Collectively, ISR-activated Gdf15 counteracts pathological processes via the protective reprogramming of the autophagic network and microbial community, thereby providing robust predictive biomarkers and interventions against renointestinal distress.

Does ankle arthrodesis induce satisfactory changes in the medial longitudinal arch height of the foot for severe varus ankle arthritis?

PURPOSE: We designed this study to determine how changes in coronal ankle alignment affect sagittal alignment of the foot. Specifically, we focused on the changes in medial longitudinal arch height, which could be reflected by the medial cuneiform height (MCH), Meary's angle, and calcaneal pitch angle (CPA). METHODS: We retrospectively analyzed the radiographic findings of 37 patients who underwent open ankle arthrodesis without inframalleolar correction (such as first metatarsal dorsal closing wedge osteotomy, calcaneal osteotomies, tendon transfers, or tarsal joint arthrodesis) of severe varus ankle arthritis. The inclusion criterion was a pre-operative tibial axis to talar dome angle of 80 degrees or less. The enrolled patients were divided into two groups according to the post-operative decrease in MCH (≥ 2 mm or < 2 mm). RESULTS: A post-operative MCH decrease of ≥ 2 mm was observed in 43.2% (16 patients). Although the degree of coronal ankle varus correction was similar, the decrease in the Meary's angle was significantly greater in the group with a post-operative MCH decrease of ≥ 2 mm than in those with < 2 mm (- 4.1 degrees vs. - 1.3 degrees, P = 0.01). The changes in CPA were not significantly different (P = 0.172). CONCLUSION: Correction of ankle varus deformity via ankle arthrodesis could lead to a decrease in the medial longitudinal arch height in less than half of the enrolled patients. In these patients, a cavus component of the foot might be an important factor in determining a successful sagittal foot alignment change, while the CPA was maintained post-operatively.

Enhanced Room-Temperature Ethanol Detection by Quasi 2D Nanosheets of an Exfoliated Polymeric Graphitized Carbon Nitride Composite-Based Patterned Sensor.

A novel room-temperature gas sensor composed of polymeric graphitic carbon nitride composite was fabricated and used for the detection of ethanol vapor under ambient conditions. Polymeric carbon nitride (PCN) microstructures composed of fluffy nanosheets were synthesized via a thermal polycondensation mechanism using melamine as the precursor, followed by vigorous chemical exfoliation. These sheet-like microstructures were employed as active materials in the form of composites, along with carbon paste consisting of graphite nanoplatelets and carbon black. The active sensing layer was fabricated on a PET sheet and assembled on an interdigitated gold electrode. The as-fabricated sensor exhibited excellent sensing efficiency (>100% response at 10 ppm) along with high selectivity and stability. In particular, for ultralow concentrations such as 1 ppm (>10% response), this resistive-based sensor exhibited a swift response time provided under ambient conditions. The exfoliated PCN composite sensor was found to be working with appreciable efficiency at moderate relative humidity (%) with the least fluctuation in response signals also demonstrating long-term stability for 30 days with consistent response signals.

Impact of the Coronavirus Disease Pandemic and Related Vaccination in an Orthopedic Clinic in the United Arab Emirates: An Observational Study.

The coronavirus disease (COVID-19) pandemic has influenced hospital visiting patterns. Although vaccination has decreased infection rates and disease severity, hospital visiting patterns and associated treatment changes related to orthopedics remain unexplored in the Middle East. Therefore, this study aimed to examine the impact of the COVID-19 pandemic and vaccination on individual departments dealing with musculoskeletal disorders in the United Arab Emirates. Relationships between publicly available national data on the number of COVID-19 polymerase chain reaction tests and confirmed and recovered cases during May 2020-July 2021 and hospital data on the number of outpatients, inpatients, operations, and physiotherapy consultations were analyzed. In January 2021, the relationship between vaccination rate and orthopedic unit utilization was evaluated after vaccination campaign initiation. Multifactorial analysis revealed that an increased number of COVID-19-related deaths correlated with a decreased number of joint operations. Negative linear relationships were observed among confirmed and death cases with inpatient treatment and joint operation as well as recovered cases with inpatient treatment. Recovered cases with inpatient treatment and joint operation showed a positive linear relationship. Inpatient spine treatment showed a positive relationship with vaccination rates. The COVID-19 pandemic influenced orthopedic treatment in the Middle East, and vaccination campaigns facilitated inpatient spine treatment.

Outcome of proximal triple derotational metatarsal osteotomy for three-dimensional correction of hallux valgus deformity.

PURPOSE: To correct hallux valgus deformities in patients with a greater pronation of the first metatarsal, we designed a novel proximal triple derotational metatarsal osteotomy (PTDMO), which could be used to achieve three-dimensional correction of hallux valgus deformities at the proximal metatarsal level. METHODS: We prospectively evaluated the radiographic and clinical outcomes of 13 consecutive cases underwent PTDMO between November 2018 and May 2020. The minimum follow-up for inclusion was 12 months. The hallux valgus angle (HVA), first-to-second intermetatarsal angle (IMA), distal metatarsal articular angle (DMAA), relative length of the second metatarsal, and medial sesamoid position on the weight bearing foot anteroposterior radiographs, and the degree of the first metatarsal pronation on forefoot axial radiographs were measured pre-operatively, at six weeks post-operatively, and at the final follow-up. The American Orthopaedic Foot and Ankle Society (AOFAS) score and Foot Ankle Outcome Scores (FAOS) were measured. RESULTS: In the comparison of pre-operative and final follow-up parameters, HVA, IMA, and DMAA were significantly improved post-operatively (all, P < 0.001). The relative length of the second metatarsal did not differ significantly post-operatively (P = 0.724). The medial sesamoid was significantly reduced (P = 0.01), and the first metatarsal pronation decreased by 10.16° (P = 0.034). Regarding clinical parameters, the AOFAS score and FAOS in all categories significantly improved post-operatively (all, P < 0.001). CONCLUSION: PTDMO resulted in satisfactory radiographic and clinical outcomes with respect to deformity correction and pain relief, with significant post-operative reduced pronation of the first metatarsal.

Light-stabilized FHA2 suppresses miRNA biogenesis through interactions with DCL1 and HYL1.

The precise regulation of microRNA (miRNA) biogenesis is crucial for plant development, which requires core microprocessors and many fine tuners to coordinate their miRNA processing activity/specificity in fluctuating cellular environments. During de-etiolation, light triggers a dramatic accumulation of core microprocessors and primary miRNAs (pri-miRNAs) but decreases pri-miRNA processing activity, resulting in relatively constant miRNA levels. The mechanisms underlying these seemingly contradictory regulatory changes remain unclear. In this study, we identified forkhead-associated domain 2 (FHA2) as a light-stabilized suppressor of miRNA biogenesis. We found that FHA2 deficiency increased the level of mature miRNAs, accompanied by a reduction in pri-miRNAs and target mRNAs. Biochemical assays showed that FHA2 associates with the core microprocessors DCL1, HYL1, and SE, forming a complex to suppress their pri-miRNA processing activity. Further analyses revealed that FHA2 promotes HYL1 binding but inhibits the binding of DCL1-PAZ-RNase-RNA-binding domains (DCL1-PRR) to miRNAs, whereas FHA2 does not directly bind to these RNAs. Interestingly, we found that FHA2 protein is unstable in the dark but stabilized by light during de-etiolation. Consistently, disruption of FHA led to defects in light-triggered changes in miRNA expression and reduced the survival rate of de-etiolated seedlings after prolonged light deprivation. Collectively, these data suggest that FHA2 is a novel light-stabilized suppressor of miRNA biogenesis and plays a role in fine-tuning miRNA processing during de-etiolation.

MRF Family Genes Are Involved in Translation Control, Especially under Energy-Deficient Conditions, and Their Expression and Functions Are Modulated by the TOR Signaling Pathway.

Dynamic control of protein translation in response to the environment is essential for the survival of plant cells. Target of rapamycin (TOR) coordinates protein synthesis with cellular energy/nutrient availability through transcriptional modulation and phosphorylation of the translation machinery. However, mechanisms of TOR-mediated translation control are poorly understood in plants. Here, we report that Arabidopsis thaliana MRF (MA3 DOMAIN-CONTAINING TRANSLATION REGULATORY FACTOR) family genes encode translation regulatory factors under TOR control, and their functions are particularly important in energy-deficient conditions. Four MRF family genes (MRF1-MRF4) are transcriptionally induced by dark and starvation (DS). Silencing of multiple MRFs increases susceptibility to DS and treatment with a TOR inhibitor, while MRF1 overexpression decreases susceptibility. MRF proteins interact with eIF4A and cofractionate with ribosomes. MRF silencing decreases translation activity, while MRF1 overexpression increases it, accompanied by altered ribosome patterns, particularly in DS. Furthermore, MRF deficiency in DS causes altered distribution of mRNAs in sucrose gradient fractions and accelerates rRNA degradation. MRF1 is phosphorylated in vivo and phosphorylated by S6 kinases in vitro. MRF expression and MRF1 ribosome association and phosphorylation are modulated by cellular energy status and TOR activity. We discuss possible mechanisms of the function of MRF family proteins under normal and energy-deficient conditions and their functional link with the TOR pathway.

Effects of core and non-dominant arm strength training on drive distance in elite golfers.

BACKGROUND: Various training schemes have sought to improve golf-related athletic ability. In the golf swing motion, the muscle strengths of the core and arms play important roles, where a difference typically exists in the power of arm muscles between the dominant and non-dominant sides. The purposes of this study were to determine the effects of exercises strengthening the core and non-dominant arm muscles of elite golf players (handicap < 3) on the increase in drive distance, and to present a corresponding training scheme aimed at improving golf performance ability. METHODS: Sixty elite golfers were randomized into the control group (CG, n = 20), core exercise group (CEG, n = 20), and group receiving a combination of muscle strengthening exercises of the non-dominant arm and the core (NCEG, n = 20). The 3 groups conducted the corresponding exercises for 8 weeks, after which the changes in drive distances and isokinetic strength were measured. RESULTS: Significant differences in the overall improvement of drive distance were observed among the groups (p < 0.001). Enhancement of the drive distance of NCEG was greater than both CG (p < 0.001) and CEG (p = 0.001). Except for trunk flexion, all variables of the measurements of isokinetic strength for NCEG also showed the highest values compared to the other groups. Examination of the correlation between drive distance and isokinetic strength revealed significant correlations of all variables except trunk flexion, wrist extension, and elbow extension. CONCLUSION: The combination of core and non-dominant arm strength exercises can provide a more effective specialized training program than core alone training for golfers to increase their drive distances.

Core-shell nanostructured hybrid composites for volatile organic compound detection.

We report a high-performance chemiresistive sensor for detection of volatile organic compound (VOC) vapors based on core-shell hybridized nanostructures of Fe3O4 magnetic nanoparticles (MNPs) and poly(3,4-ethylenedioxythiophene) (PEDOT)-conducting polymers. The MNPs were prepared using microwave-assisted synthesis in the presence of polymerized ionic liquids (PILs), which were used as a linker to couple the MNP and PEDOT. The resulting PEDOT-PIL-modified Fe3O4 hybrids were then explored as a sensing channel material for a chemiresistive sensor to detect VOC vapors. The PEDOT-PIL-modified Fe3O4 sensor exhibited a tunable response, with high sensitivity (down to a concentration of 1 ppm) and low noise level, to VOCs; these VOCs include acetone vapor, which is present in the exhaled breath of potential lung cancer patients. The present sensor, based on the hybrid nanostructured sensing materials, exhibited a 38.8% higher sensitivity and an 11% lower noise level than its PEDOT-PIL-only counterpart. This approach of embedding MNPs in conducting polymers could lead to the development of new electronic noses, which have significant potential for the use in the early diagnosis of lung cancer via the detection of VOC biomarkers.

Lateral meniscus allograft transplantation: an arthroscopically-assisted single-incision technique using all-inside sutures with a suture hook.

We present an arthroscopically-assisted single-incision technique using all-inside sutures with a suture hook in the lateral meniscus allograft transplantation. Although this technique is technically demanding, it provides vertically oriented and secure sutures with good tissue approximation without the accessory skin incision.

Treatment of brachymetatarsia by distraction osteogenesis.

Metatarsal lengthening by distraction osteogenesis was performed on 17 brachymetatarsia patients with 39 metatarsal bones. To lengthen the first metatarsal in an attempt to prevent development of varus deformity of the hindfoot after lengthening, horizontal lengthening in the anterior direction was performed rather than lengthening through the anatomical axis. In addition, care was taken to ensure that the fourth metatarsal bone screw did not interpose with the fifth extensor tendon during the fourth metatarsal lengthening. Lengthening was successful except in 1 case with mean lengthening of 19.5 mm (48.8%) for the first metatarsal and 17.1 mm (36.2%) for the fourth metatarsal. Because of joint stiffness, plantar capsulotomy was performed on 7 cases, 6 of which had been previously operated on bilaterally. Varus deformity of the hindfoot after the first metatarsal lengthening and entrapment of the fifth extensor tendon after the fourth metatarsal lengthening was not detected in any case.

Treatment of congenital muscular torticollis in patients older than 8 years.

The authors treated congenital muscular torticollis by sternocleidomastoid muscle release in 32 patients over 8 years of age who had not received any prior medical treatment or in whom torticollis had recurred since initial treatment. The results were analyzed to compare clinical results after an average of 39 months (range 24-74 months) by dividing the patients into two groups: patients who were still in the growing period (group 1, n=19) and patients who had finished growth (group 2, n = 13) at surgery. According to the total score table by Cheng et al (which includes motion deficits, craniofacial asymmetry, scar, band, head tilt, and subjective assessment), there were 13 excellent and 6 good results in group 1 and 2 excellent, 8 good, and 3 fair results in group 2. The clinical results were statistically less successful in group 2 than in group 1 by Cheng's score table (P <0.05). However, most patients showed marked improvement in neck motion and head tilt, with satisfactory functional and cosmetic results. Thus, in patients older than school age, even for those who have finished growth, sufficient unipolar or bipolar release of the sternocleidomastoid muscle and intensive postoperative care are expected to yield satisfactory treatment results.