CcNFYB3-CcMATE35 and LncRNA CcLTCS-CcCS modules jointly regulate the efflux and synthesis of citrate to enhance aluminium tolerance in pigeon pea.

Aluminium (Al) toxicity decreases crop production in acid soils in general, but many crops have evolved complex mechanisms to resist it. However, our current understanding of how plants cope with Al stress and perform Al resistance is still at the initial stage. In this study, the citrate transporter CcMATE35 was identified to be involved in Al stress response. The release of citrate was increased substantially in CcMATE35 over-expression (OE) lines under Al stress, indicating enhanced Al resistance. It was demonstrated that transcription factor CcNFYB3 regulated the expression of CcMATE35, promoting the release of citrate from roots to increase Al resistance in pigeon pea. We also found that a Long noncoding RNA Targeting Citrate Synthase (CcLTCS) is involved in Al resistance in pigeon pea. Compared with controls, overexpression of CcLTCS elevated the expression level of the Citrate Synthase gene (CcCS), leading to increases in root citrate level and citrate release, which forms another module to regulate Al resistance in pigeon pea. Simultaneous overexpression of CcNFYB3 and CcLTCS further increased Al resistance. Taken together, these findings suggest that the two modules, CcNFYB3-CcMATE35 and CcLTCS-CcCS, jointly regulate the efflux and synthesis of citrate and may play an important role in enhancing the resistance of pigeon pea under Al stress.

Porphyrin-Based Metal-Organic Framework Materials: Design, Construction, and Application in the Field of Photocatalysis.

Metal-organic frameworks (MOFs) are a novel category of porous crystalline materials with an exceptionally high surface area and adjustable pore structure. They possess a designable composition and can be easily functionalized with different units. Porphyrins with conjugated tetrapyrrole macrocyclic structures can absorb light from ultraviolet to visible light regions, and their structures and properties can be facilely regulated by altering their peripheral groups or central metal ions. Porphyrin-based MOFs constructed from porphyrin ligands and metal nodes combine the unique features of porphyrins and MOFs as well as overcoming their respective limitations. This paper reviewed the design and construction, light absorption and charge transfer pathways, and strategy for improving the photocatalytic performance of porphyrin-based MOFs, and highlighted the recent progress in the field of CO2 reduction, hydrogen evolution, organic synthesis, organic pollutant removal, and nitrogen fixation. The intrinsic relationships between the structure and the property of porphyrin-based MOFs received special attention, especially the relationships between the arrangements of porphyrin ligands and metal nods and the charge transfer mechanism. We attempted to provide more valuable information for the design and construction of advanced photocatalysts in the future. Finally, the challenges and future perspectives of the porphyrin-based MOFs are also discussed.

Dual Channel Emissions of Kasha and Anti-Kasha from a Single Radical Molecule.

Stable open-shell luminescent radicals have recently attracted much attention due to their unique luminescence properties. However, a radical molecule with both Kasha and anti-Kasha doublet emission properties has not been reported. Herein, we have successfully synthesized a stable chlorine-substituted Chichibabin's hydrocarbon, TTM-TTM, along with its mono-radical counterpart, TTM-HTTM. The emission of TTM-TTM follows Kasha's rule in the near infrared region. However, TTM-HTTM shows dual channel doublet emissions of Kasha and anti-Kasha. Remarkably, these two types of emission compete dynamically in both solution and condensed states. Our findings provide valuable insights into the rational design and discovery of stable radicals that possess distinctive luminescent properties, thus broadening the horizons of luminescent materials research.

RNA-binding proteins and cancer metastasis.

RNA-binding proteins (RBPs) can regulate gene expression through post-transcriptionally influencing all manner of RNA biology, including alternative splicing (AS), polyadenylation, stability, and translation of mRNAs, as well as microRNAs (miRNAs) and circular RNAs (circRNAs) processing. There is accumulating evidence reinforcing the perception that dysregulation or dysfunction of RBPs can lead to various human diseases, including cancers. RBPs influence diverse cancer-associated cellular phenotypes, such as proliferation, apoptosis, senescence, migration, invasion, and angiogenesis, contributing to the initiation and development of tumors, as well as clinical prognosis. Metastasis is the leading cause of cancer-related recurrence and death. Therefore, it is necessary to elucidate the molecular mechanisms behind tumor metastasis. In fact, a growing body of published research has proved that RBPs play pivotal roles in cancer metastasis. In this review, we will summarize the recent advances for helping us understand the role of RBPs in tumor metastasis, and discuss dysfunctions and dysregulations of RBPs affecting metastasis-associated processes including epithelial-mesenchymal transition (EMT), migration, and invasion of cancer cells. Furthermore, we will discuss emerging RBP-based strategy for the treatment of cancer metastasis.

Pocket-Size Wireless Nanoelectrospray Ionization Mass Spectrometry for Metabolic Analysis of Salty Biofluids and Single Cells.

Analysis of volume-limited biological samples such as single cells and biofluids not only benefits clinical purposes but also promotes fundamental research in life sciences. Detection of these samples, however, imposes strict requirements on measurement performance because of the minimal volume and concentrated salts of the samples. Herein, we developed a self-cleaning nanoelectrospray ionization device powered by a pocket-size "MasSpec Pointer" (MSP-nanoESI) for metabolic analysis of salty biological samples with limited volume. The self-cleaning effect induced by Maxwell-Wagner electric stress helps with keeping the borosilicate glass capillary tip free from clogging and thus increasing salt tolerance. This device possesses a high sample economy (about 0.1 µL per test) due to its pulsed high voltage supply, sampling method (dipping the nanoESI tip into analyte solution), and contact-free electrospray ionization (ESI) (the electrode does not touch the analyte solution during ESI). High repeatable results could be acquired by the device with a relative standard deviation (RSD) of 1.02% for voltage output and 12.94% for MS signals of caffeine standard. Single MCF-7 cells were metabolically analyzed directly from phosphate buffered saline, and two types of untreated cerebrospinal fluid from hydrocephalus patients were distinguished with 84% accuracy. MSP-nanoESI gets rid of the bulky apparatus and could be held in hand or put into one's pocket for transportation, and it could operate for more than 4 h without recharge. We believe this device will boost scientific research and clinical usage of volume-limited biological samples with high-concentration salts in a low-cost, convenient, and rapid manner.

RNA demethylase ALKBH5 inhibits TGF-ß-induced EMT by regulating TGF-ß/SMAD signaling in non-small cell lung cancer.

AlkB homolog 5 (ALKBH5) has been revealed as a key RNA N6 -methyladenosine (m6 A) demethylase that is implicated in development and diseases. However, the function of ALKBH5 in TGF-ß-induced epithelial-mesenchymal transition (EMT) and tumor metastasis of non-small-cell lung cancer (NSCLC) remains unknown. Here, we firstly show that ALKBH5 expression is significantly reduced in metastatic NSCLC. ALKBH5 overexpression inhibits TGF-ß-induced EMT and invasion of NSCLC cells, whereas ALKBH5 knockdown promotes the corresponding phenotypes. ALKBH5 overexpression suppresses TGF-ß-stimulated NSCLC cell metastasis in vivo. ALKBH5 overexpression decreases the expression and mRNA stability of TGFßR2 and SMAD3 but increases those of SMAD6, while ALKBH5 knockdown causes the opposite results. Importantly, ALKBH5 overexpression or knockdown leads respectively to an attenuated or augmented phosphorylation of SMAD3, an indispensable downstream effector that activates TGF-ß/SMAD signaling. Moreover, m6 A-binding proteins YTHDF1/3 promotes TGFßR2 and SMAD3 expression, and YTHDF2 inhibits SMAD6 expression. YTHDF1/2/3 facilitates TGF-ß-stimulated EMT and invasion of NSCLC cells. Mechanistically, ALKBH5 affects TGFßR2, SMAD3 and SMAD6 expression and mRNA stability by erasing m6 A modification in NSCLC cells. ALKBH5 weakens YTHDF1/3-mediated TGFßR2 and SMAD3 mRNA stabilization, and abolishes YTHDF2-mediated SMAD6 mRNA degradation, supporting the notion that ALKBH5 inhibits TGF-ß-induced EMT and invasion of NSCLC cells via YTHD1/2/3-mediated mechanism. Taken together, our findings highlight an important role of ALKBH5 in regulating TGF-ß/SMAD signaling, and establish a mechanistic interaction of ALKBH5 with TGFßR2/SMAD3/SMAD6 for controlling TGF-ß-induced EMT in NSCLCs.

Quaking 5 suppresses TGF-ß-induced EMT and cell invasion in lung adenocarcinoma.

Quaking (QKI) proteins belong to the signal transduction and activation of RNA (STAR) family of RNA-binding proteins that have multiple functions in RNA biology. Here, we show that QKI-5 is dramatically decreased in metastatic lung adenocarcinoma (LUAD). QKI-5 overexpression inhibits TGF-ß-induced epithelial-mesenchymal transition (EMT) and invasion, whereas QKI-5 knockdown has the opposite effect. QKI-5 overexpression and silencing suppresses and promotes TGF-ß-stimulated metastasis in vivo, respectively. QKI-5 inhibits TGF-ß-induced EMT and invasion in a TGFßR1-dependent manner. KLF6 knockdown increases TGFßR1 expression and promotes TGF-ß-induced EMT, which is partly abrogated by QKI-5 overexpression. Mechanistically, QKI-5 directly interacts with the TGFßR1 3' UTR and causes post-transcriptional degradation of TGFßR1 mRNA, thereby inhibiting TGF-ß-induced SMAD3 phosphorylation and TGF-ß/SMAD signaling. QKI-5 is positively regulated by KLF6 at the transcriptional level. In LUAD tissues, KLF6 is lowly expressed and positively correlated with QKI-5 expression, while TGFßR1 expression is up-regulated and inversely correlated with QKI-5 expression. We reveal a novel mechanism by which KLF6 transcriptionally regulates QKI-5 and suggest that targeting the KLF6/QKI-5/TGFßR1 axis is a promising targeting strategy for metastatic LUAD.

First Report of Lasiodiplodia theobromae Causing Brown Leaf Spot on Bruguiera gymnorrhiza in China.

Bruguiera gymnorrhiza (Linn.) Sav. is a dominant tree species of mangrove forests in tropical coastal areas of China. This species is commonly used for the greening of tidal flats and seawalls in tropical and subtropical regions (Allen, & Duke 2000). A survey that was conducted from August to September 2020, in the mangrove national nature reserve at Zhanjiang, Guangdong Province, South China. Brown leaf spot symptoms were observed on Bruguiera gymnorrhiza and disease incidence was over 10% (200 investigated trees). Symptomatic small spots initially appeared at the middle or edges of leaves, enlarged irregularly, and developed into brown necrotic spots with dying curly edges. The color of the lesion's center changed to dark brown or gray. To identify the causative agent, twenty diseased leaves were sampled for pathogen isolation. Affected foliar tissues cut into 5 × 5 mm pieces, disinfected in 75% ethanol for 2 mins, rinsed in sterile distilled water, and then air dried under a sterilized filter paper. Leaf pieces were plated onto potato dextrose agar (PDA) in Petri dishes and then incubated at 28°C in darkness for 3-5 days. Hyphal tips of fungal colonies growing from the tissue pieces were subcultured onto fresh PDA to obtain pure single hyphae cultures. The fungal colonies were initially composed of white aerial mycelia, but turned gray after 7 days. Immature conidia were hyaline, subovoid, and aseptate while mature conidia becoming dark brown, one-septate with longitudinal stripes, the length/width ratio is 19.98 to 29.50 µm (average 24.37 µm; n = 50) × 11.99 to 14.45 µm (average 13.09 µm; n = 50). On the basis of morphological features all isolates were identified as Lasiodiplodia theobromae (Pat.) Griffon & Maubl (Alves et al. 2008). For DNA-based identification, the internal transcribed spacer (ITS) region gene and fragment of elongation factor 1-alpha (EF1-α) gene of the three isolates were amplified and sequenced following the methods described in a previous study (White et al. 1990, Carbone & Kohn 1999). The obtained sequences of ITS and EF1-α were deposited in GenBank with accession numbers OK644200 and OL345571. The BLAST results showed at least 99.60% similarity with the sequences of Lasiodiplodia theobromae (ITS, MT644474.1 [99.79%]; EF1-a, MK961975.1 [99.60%]). To fulfill Koch's postulates, PDA plugs with actively growing mycelium of the isolates were inoculated on the leaves of Bruguiera gymnorrhiza plants that were wounded by using a sterilized needle or scalpel. Inoculated leaves were covered with sterilized wet cotton, and the plants were kept at 28°C and 80% relative humidity. The inoculated plants showed leaf spot symptoms that were similar to those previously observed in the field after 1-2 days, whereas control leaves remained healthy. Lasiodiplodia theobromae was consistently isolated from inoculated leaves again. Lasiodiplodia theobromae (Botryosphaeriaceae) is a plurivorous pathogen in a wide variety of hosts, mostly prevalent in tropical and subtropical climate regions. It has been previously reported to cause brown leaf spot on Broussonetia papyrifera (Luo et al. 2020), foliar diseases on Camellia oleifera (Zhu et al. 2014) and Kadsura longipedunculata (Fan et al. 2020). To our knowledge, this is the first report of Lasiodiplodia theobromae causing brown leaf spot on Bruguiera gymnorrhiza plants in China and worldwide. Our findings will help to make management strategies for control of this disease on Bruguiera gymnorrhiza.

Introduction of 3D-classification and its derived surgical sequence of Schatzker type IV tibial plateau fractures.

INTRODUCTION: Schatzker IV tibial plateau fractures usually have a worse prognosis due to their high variability and the accompanied bony and soft tissue injuries. This study aimed to introduce an injury mechanism-based new classification of Schatzker IV tibial plateau fractures and evaluate its reliability. Additionally, this study aimed to evaluate the outcomes of operative Schatzker IV tibial plateau fractures treated according to the surgical sequences determined by the new classification. MATERIALS AND METHODS: A total of 63 cases of operative Schatzker IV tibial plateau fractures that were treated following the new surgical sequences were enrolled in our study. The CT images of these patients were reviewed and classified twice according to the new 3D classification by 4 independent observers. The reliability of the classification was calculated through kappa analysis. The classification-determined surgical sequence was evaluated by observing the postoperative efficacy during the follow-up. RESULTS: Both the intra-observer (the mean k = 0.897, CI 0.806-0.971) and inter-observer (the mean k = 0.883, CI 0.786-0.961) reliability of 3D-classification showed excellent agreement according to Landis and Koch. All the patients were followed up for 6-28 months (average 12.8 months). As for the evaluation of the postoperative efficacy, according to KSS, 53 cases were rated as excellent, 8 cases as good, and 2 cases as fair results. CONCLUSIONS: The new proposed classification showed high intra-observer and inter-observer reliability in our study. The surgical sequence determined by the classification can help surgeons to acquire good reduction and rigid internal fixation. Therefore the new classification of Schatzker IV tibial plateau fractures and the derived surgical sequences are worthy of further popularization and application in clinical trials.

Bio-Inspired Hydrogel-Elastomer Actuator with Bidirectional Bending and Dynamic Structural Color.

In nature, some creatures can change their body shapes and surface colors simultaneously to respond to the external environments, which greatly inspired researchers in the development of color-tunable soft actuators. In this work, we present a facile method to prepare a smart hydrogel actuator that can bend bidirectionally and change color simultaneously, just like an octopus. The actuator is fabricated by elastomer/hydrogel bilayer and the hydrogel layer was decorated with thermoresponsive microgels as the photonic crystal blocks. Compared with the previously reported poly(N-isopropylacrylamide) hydrogel-based bilayer hydrogel actuators, which are generally limited to one-directional deformation, the elastomer/hydrogel bilayer actuator prepared in our work exhibits unique bidirectional bending behavior in accordance with the change of structural color. The bending degrees can be changed from -360° to 270° in response to solution temperatures ranging from 20 °C to 60 °C. At the same time, the surface color changes from red to green, and then to blue, covering the full visible light spectrum. The bending direction and degree of the hydrogel actuator can easily be adjusted by tuning the layer thickness ratio of the elastomer/hydrogel or the composition of the hydrogel. The color-tunable hydrogel-elastomer actuator reported in this work can achieve both programmable deformations and color-changing highly resembling the natural actuating behaviors of creatures.

Comparison of clinical effects of two surgical approaches in the treatment of acetabular fractures.

Objective: To determine the clinical effect of lateral rectus abdominis approach and modified Stoppa approach for the surgical treatment of acetabular fractures. Methods: A retrospective analysis was performed on the case data of 30 patients with acetabular fractures admitted to the Department of Orthopaedics of Hengshui City People's Hospital from June 2017 to June 2021. According to the surgical methods, the enrolled patients were divided into the lateral rectus abdominis approach group (observation group) and the modified Stoppa approach group (control group), with 15 patients in each group. Further comparison was made on the incision length, operation time, intraoperative blood loss, length of stay in the hospital, fracture reduction, hip joint function, neurological recovery, and postoperative complications between the two groups. Results: There was no significant difference between the two groups in the length of stay in the hospital, hip joint function score, fracture reduction quality, and excellent-to-good rate of hip joint function (p>0.05). There were significant differences in incision length, intraoperative blood loss, operation time, postoperative motor and touch function scores, and postoperative complication rate between the observation group and the control group (p<0.05). Conclusion: The clinical effect of the lateral rectus abdominis approach is close to that of the modified Stoppa approach for the surgical treatment of acetabular fracture patients. However, and importantly, surgery through the lateral rectus abdominis approach has less trauma, shorter operation time, lower surgical complications, and good postoperative functional recovery.

Combined transcriptome and metabolome analysis of Nerium indicum L. elaborates the key pathways that are activated in response to witches' broom disease.

BACKGROUND: Nerium indicum Mill. is an ornamental plant that is found in parks, riversides, lakesides, and scenic areas in China and other parts of the world. Our recent survey indicated the prevalence of witches' broom disease (WBD) in Guangdong, China. To find out the possible defense strategies against WBD, we performed a MiSeq based ITS sequencing to identify the possible casual organism, then did a de novo transcriptome sequencing and metabolome profiling in the phloem and stem tip of N. indicum plants suffering from WBD compared to healthy ones. RESULTS: The survey showed that Wengyuen county and Zengcheng district had the highest disease incidence rates. The most prevalent microbial species in the diseased tissues was Cophinforma mamane. The transcriptome sequencing resulted in the identification of 191,224 unigenes of which 142,396 could be annotated. There were 19,031 and 13,284 differentially expressed genes (DEGs) between diseased phloem (NOWP) and healthy phloem (NOHP), and diseased stem (NOWS) and healthy stem (NOHS), respectively. The DEGs were enriched in MAPK-signaling (plant), plant-pathogen interaction, plant-hormone signal transduction, phenylpropanoid and flavonoid biosynthesis, linoleic acid and α-linoleic acid metabolism pathways. Particularly, we found that N. indicum plants activated the phytohormone signaling, MAPK-signaling cascade, defense related proteins, and the biosynthesis of phenylpropanoids and flavonoids as defense responses to the pathogenic infection. The metabolome profiling identified 586 metabolites of which 386 and 324 metabolites were differentially accumulated in NOHP vs NOWP and NOHS and NOWS, respectively. The differential accumulation of metabolites related to phytohormone signaling, linoleic acid metabolism, phenylpropanoid and flavonoid biosynthesis, nicotinate and nicotinamide metabolism, and citrate cycle was observed, indicating the role of these pathways in defense responses against the pathogenic infection. CONCLUSION: Our results showed that Guangdong province has a high incidence of WBD in most of the surveyed areas. C. mamane is suspected to be the causing pathogen of WBD in N. indicum. N. indicum initiated the MAPK-signaling cascade and phytohormone signaling, leading to the activation of pathogen-associated molecular patterns and hypersensitive response. Furthermore, N. indicum accumulated high concentrations of phenolic acids, coumarins and lignans, and flavonoids under WBD. These results provide scientific tools for the formulation of control strategies of WBD in N. indicum.

The mechanisms and cross-protection of trained innate immunity.

In recent years, the traditional cognition of immunological memory being specific to adaptive immunity has been challenged. Innate immunity can mount enhanced responsiveness upon secondary stimulation, and a phenomenon is termed trained innate immunity. Trained innate immunity is orchestrated by distinct metabolic and epigenetic reprogramming in both circulating myeloid cells and myeloid progenitor cells in bone marrow, leading to long-term resistance to related and non-related pathogens infections. The induction of trained innate immunity can also polarize innate immune cells towards a hyperresponsive phenotype in the tumor microenvironment to exert antitumor effects. This review will discuss the current understanding of innate immune memory and the mechanisms during the induction of innate immunity, including signaling pathways, metabolic changes, and epigenetic rewriting. We also provide an overview of cross-protection against infectious diseases and cancers based on trained innate immunity.

Celastrol Attenuates Angiotensin II-Induced Cardiac Remodeling by Targeting STAT3.

RATIONALE: Excessive Ang II (angiotensin II) levels lead to a profibrotic and hypertrophic milieu that produces deleterious remodeling and dysfunction in hypertension-associated heart failure. Agents that disrupt Ang II-induced cardiac dysfunction may have clinical utility in the treatment of hypertension-associated heart failure. OBJECTIVE: We have examined the potential effect of celastrol-a bioactive compound derived from the Celastraceae family-on Ang II-induced cardiac dysfunction. METHODS AND RESULTS: In rat primary cardiomyocytes and H9C2 (rat cardiomyocyte-like H9C2) cells, celastrol attenuates Ang II-induced cellular hypertrophy and fibrotic responses. Proteome microarrays, surface plasmon resonance, competitive binding assays, and molecular simulation were used to identify the molecular target of celastrol. Our data showed that celastrol directly binds to and inhibits STAT (signal transducer and activator of transcription)-3 phosphorylation and nuclear translocation. Functional tests demonstrated that the protection of celastrol is afforded through targeting STAT3. Overexpression of STAT3 dampens the effect of celastrol by partially rescuing STAT3 activity. Finally, we investigated the in vivo effect of celastrol treatment in mice challenged with Ang II and in the transverse aortic constriction model. We show that celastrol administration protected heart function in Ang II-challenged and transverse aortic constriction-challenged mice by inhibiting cardiac fibrosis and hypertrophy. CONCLUSIONS: Our studies show that celastrol inhibits Ang II-induced cardiac dysfunction by inhibiting STAT3 activity.

Hypothermic oxygenated perfusion ameliorates ischemia-reperfusion injury of fatty liver in mice via Brg1/Nrf2/HO-1 axis.

BACKGROUND: After cold storage (CS) and subsequent transplantation, fatty liver is more inclined to develop liver dysfunction and serious postoperative complications in contrast to healthy liver. Hypothermic oxygenated perfusion (HOPE) is a safe and efficacious system, which can repair fatty liver and reduce ischemia-reperfusion injury. The aim of this research is to investigate the function of Brg1/Nrf2/HO-1 signaling pathway in the protective effect of HOPE on ischemia-reperfusion injury of fatty liver. METHODS: The mouse fatty liver model was successfully established and verified by hematoxylin-eosin (HE) staining and oil red O staining. The animals were divided into Control group, CS group and HOPE group. The levels of liver enzyme and lactate in the perfusate were used to measure liver function and cellular metabolism. HE staining and TUNEL staining were utilized to assess the tissue structure and apoptosis, respectively. The levels of superoxide dismutase, malondialdehyde and reactive oxygen species in liver tissue were measured to quantitatively analyze the degree of oxidative stress, and the expressions of protein Brg1, Nrf2 and HO-1 were detected by means of the western blot. Double-labeling immunofluorescence was to explore the colocalization of Brg1 and Nrf2. RESULTS: The injury of the liver in the CS group was more serious than that in the control group. However, HOPE could significantly reduce the injury, which was manifested by the improvement of liver function and cellular metabolism, and the lower degrees of apoptosis, necrosis and oxidative stress. Furthermore, the expressions of Brg1, Nrf2 and HO-1 in the HOPE group were significantly increased than those in the CS group. CONCLUSIONS: One-hour HOPE treatment before reperfusion can obviously improve the injury of fatty liver in mice. The underlying mechanism may be that the interaction of Brg1 and Nrf2 can selectively activate the transcription of HO-1.

Worldwide cancer statistics of adults over 75 years old in 2019: a systematic analysis of the global burden of disease study 2019.

BACKGROUND AND PURPOSE: Cancer has become one of the major killers of humanity due to the number of people over the age of 75 increasing with population ageing. The aim of this study was to analyse the incidence and mortality rates in people over 75 of 29 cancer types in 204 countries and regions, as well as the trends from 1990 to 2019. METHODS: Twenty-nine cancer types were collected from the Global Burden of Disease (GBD) 2019 database( https://vizhub.healthdata.org/gbd-results/ ). We collected global cancer data for 2019 in terms of sex, age, sociodemographic index (SDI), region, etc. The estimated annual percentage change (EAPC) was calculated to assess the trend of the cancer incidence and mortality rate from 1990 to 2019. RESULTS: In 2019, the number of new cancer cases and deaths among people 75 and older was almost 3 and 4.5 times that of 1990, respectively. From 1990 to 2019, there was a slow rise in incidence and a slight decline in mortality. There were significant differences in the cancer burden based on sex, age, region, and SDI. The cancer burden in men was higher than in women. In addition, the cancer burden varied from region to region. The highest cancer burden occurred in high-income North America. In addition, the higher the SDI was, the greater the burden of cancer. The incidence of cancer in high SDI was approximately seven times that of low SDI, and the trend of increase in high SDI was obvious. However, the trend of mortality in high SDI was decreasing, while it was increasing in low SDI. CONCLUSIONS: The present study focused on the cancer burden in adults over 75 years old. The findings in the study could serve as the basis for an analysis of the types of cancers that are most prevalent in different regions. This is beneficial for strategies of prevention and treatment according to the characteristics of different countries and regions to reduce the burden of cancer in older adults.

Can Traditional Straight-leg Swaddling Influence Developmental Dysplasia of the Femoral Trochlea? An In Vivo Study in Rats.

BACKGROUND: It has been reported that trochlear dysplasia occurs very early in development, and environmental factors like swaddling may cause developmental dysplasia of the hip, which is associated with a shallower trochlear groove. However, to our knowledge, there are no definitive studies about the relationship between trochlear dysplasia and traditional straight-leg swaddling. QUESTIONS/PURPOSES: Using a rat model of femoral trochlear dysplasia, we asked: Does straight-leg swaddling for 1 and 2 weeks in newborn Wistar rats alter the femoral trochlea with respect to (1) gross morphology, (2) histologic appearance, as well as (3) trochlear sulcus angle, width, and depth? METHODS: Eighty-four newborn Wistar rats (44 females and 40 males) were divided into two equal groups: 42 in the unswaddled group and 42 in the swaddled group; each group was comprised of 22 females and 20 males. In the swaddled group, the rats were wrapped in surgical tape to maintain hip and knee extension to simulate traditional human straight-leg swaddling. To determine whether longer periods of swaddling were associated with more severe trochlear dysplasia, 21 rats in each group were euthanized at 1 and 2 weeks, respectively, and the gross morphology of the femoral trochlea was observed by one observer blinded to condition. Then hematoxylin and eosin staining of the femoral trochlea was performed and the distribution and number of the chondrocytes of the trochlear groove were viewed through a microscope. The trochlear sulcus angles, depth, and width were measured by an experienced technician blinded to condition. RESULTS: By observing the gross morphology, we found that the trochlear groove in the swaddled group became qualitatively flatter compared with the unswaddled group at 1 week, and at 2 weeks, the trochlear groove became much shallower. At 1 and 2 weeks, histologic examinations showed obvious qualitative changes in the distribution and number of chondrocytes of the trochlear groove in the swaddled than in the unswaddled groups. In the swaddled group, trochlear dysplasia was more common at 2 weeks, occurring in 62% (26 of 42 [16 of 22 females and 10 of 22 males]) versus 33% (14 of 42 [8 of 22 females and 6 of 20 males]) at 1 week. At 1 week, the swaddled group showed more trochlear dysplasia compared with the unswaddled group as measured by angle of the trochlear groove (137° ± 6° versus 132°± 3.6°, mean difference 5° [95% confidence interval 2.9° to 7.2°]; p < 0.001), depth of the trochlear grove (0.28 ± 0.04 mm versus 0.31 ± 0.02 mm, mean difference 0.03 mm [95% CI 0.01 to 0.04]; p < 0.001). At 2 weeks, the swaddled group showed more severe trochlear dysplasia than at 1 week compared with the unswaddled group as measured by the angle of the trochlear groove (135° ± 6.0° versus 128° ± 4.8°, mean difference 7° [95% CI 5.7° to 10.4°]; p < 0.001), depth of the trochlear grove (0.32 ± 0.04 mm versus 0.36 ± 0.02 mm, mean difference 0.04 mm [95% CI 0.03 to 0.06]; p < 0.001). There was no difference in the width of the trochlear sulcus between the swaddled and the unswaddled groups at 1 week (1.29 ± 0.14 mm versus 1.30 ± 0.12 mm, mean difference 0.01 mm [95% CI -0.05 to 0.07]; p = 0.73) and 2 weeks (1.55 ± 0.12 mm versus 1.56 ± 0.12 mm, mean difference 0.01 mm [95% CI -0.05 to 0.07]; p = 0.70). CONCLUSION: Our results indicate that traditional straight-leg swaddling could induce trochlear dysplasia in this model of newborn rats. With an increased swaddling time of 2 weeks, more severe trochlear dysplasia appeared in the swaddled group. CLINICAL RELEVANCE: Our findings suggest that traditional straight-leg swaddling may impair trochlear development in the human neonate and lead to trochlear dysplasia in infants. We believe our animal model will be useful in future work to observe and study the change of cartilage and subchondral bone in each stage of the development of trochlear dysplasia and the change of mechanotransduction-associated proteins (such as, TRPV4/ Piezo1 and CollagenⅡ) in cartilage and subchondral osteocytes. It will also be helpful to further investigate the mechanism of developmental femoral trochlea dysplasia caused by biomechanical changes.

What is the relationship between the breech presentation and femoral trochlear dysplasia? An experimental study of the breech presentation model in neonatal rats.

BACKGROUND: The relationship between breech presentation and trochlear dysplasia has been confirmed. However, the pathological process of breech-related trochlear dysplasia remains unclear. This study aimed to establish an animal model to simulate breech presentation and to analyze the pathological process of the femoral trochlea. MATERIALS AND METHODS: One hundred and twenty neonatal rats were randomly assigned into a control group and two experimental groups that were swaddled (using surgical tape) to keep the hip flexed and knees extended to simulate human breech presentation for the 5 days (short Swaddling) and the 10 days (prolonged Swaddling) of life. Gross and cross-sectional observation, histological staining measurement in two experimental time points (5 and 10 days after birth) were conducted to evaluate the morphological changes of the femoral trochlea. RESULTS: The incidence of trochlear dysplasia increased with the Swaddling time. Rats in the prolonged Swaddling group had the high prevalence of trochlea dysplasia (52 of 60), followed by short Swaddling group (42 of 60). Gross and cross-sectional observation showed a shallower trochlea groove in two experimental groups. Histologicalstaining measurement indicated that the trochlear sulcus angle and trochlear sulcus depth were significantly different between the experimental group and the control group since day 5 and day 10. CONCLUSION: In this model, breech presentation had an adverse effect on neonatal knees and could induce trochlear dysplasia. In addition, this study also showed that the more time in breech presentation, the more incidence of trochlear dysplasia.

Characteristics of clinical trials related to hip fractures and factors associated with completion.

BACKGROUND: This study aimed at investigating the characteristics of clinical trials related to hip fractures that were registered at ClinicalTrials.gov. It also aimed to identify potential risk factors associated with completion. MAIN BODY: We obtained 733 clinical studies related to hip fractures from the ClinicalTrials.gov database and included 470 studies in the analysis. These clinical trials were divided into behavioral, drug/biological, device, procedure, and other categories based on intervention types. Clinical trials investigating drugs or biologics were categorized based on the specific agents administered in each trial. Multiple logistic and Cox regression models were used to test the ability of 24 potential risk factors in predicting recruitment status and completion time, respectively. Among the included clinical trials, 44.89% (211/470) had complete recruitment status. The overall median completion time was 931.00 days (95% confidence interval [CI]: 822.56-1039.44 days). The results of only 8.94% (42/470) of clinical trials were presented on the ClinicalTrials.gov website. Bupivacaine (a local anesthetic) was most commonly investigated (in 25 clinical trials); this was followed by ropivacaine (another local anesthetic, 23 clinical trials) and tranexamic acid (a hemostatic, 21 clinical trials). Multivariate analysis showed that trials including children (P = 0.03) and having National Institutes of Health funds (P < 0.01) had significantly higher rates of complete recruitment. Higher enrollment (P < 0.01), National Institutes of Health funding (P < 0.01), location in the United States (P = 0.04), and location in Europe (P = 0.03) predisposed to longer completion time, while studies involving drugs/biologics (P < 0.01) had shorter completion times. CONCLUSIONS: A considerable proportion of clinical trials related to hip fractures were completed, but the results of only a small fraction were presented on the ClinicalTrials.gov website. The commonly investigated drugs focused on anesthesia, pain relief, and hemostasis. Several independent risk factors that affect recruitment status and completion time were identified. These factors may guide the design of clinical trials relating to hip fractures.

First Report of Phytoplasma Belongs to 16SrV Group Associated with Witches'-broom Disease of Taxillus chinensis in China.

Taxillus chinensis (DC.) Danser is a hemiparasitic shrub, widespread in Southern China (Fu et al., 2001). T. chinensis can parasitize a wide range of species (e.g., Camellia spp., Ficus virens and Osmanthus fragrans), which obviously suppressed host growth by robbing nutrient and water through haustorium, causing considerable tree damage. During field visits to Dongguan (22°86'N, 13°97'E) and Guangzhou (23°19'N, 113°31'E), Guangdong Province, in April-July 2021, the typical phytoplasma-suspected symptom manifested as stunting, leaflet, leaf chlorosis and witches'-broom were observed in almost 36% of T. chinensis plants. Leaf samples were collected from six randomly collected plants with symptoms and six symptomless plants (Fig 1). Among them, half of T. chinensis plants parasitized on the host Elaeocarpus sylvestris, the other half on the O. fragrans. No apparent symptoms were observed on both two host plants. Total DNA was extracted from 0.5 g fresh leaf of T. chinensis plants with and without symptoms, as well as two host plants E. sylvestris and O. fragrans, using the CTAB method (Doyle et al., 1990). Nested polymerase chain reactions (PCRs) were performed on DNA extracts of all tested plants with primer pairs of P1/P7 and R16mF2/R16mR1 for 16S rRNA gene (Lee et al., 1993) and rp(v)F1/rpR1 for rp gene (Lee et al., 1998). All amplicons were obtained from symptomatic samples of T. chinensis and host plant E. sylvestris, whereas no such products resulted from DNAs of symptomless plants and O. fragrans. The amplicons were purified and sequenced by Sanger method (Rui Biotech, Guangzhou, China). The amplicon of 16S rRNA and rp genes is 1346 bp and 938 bp, respectively. BLAST comparison of the 16S rRNA (accession no. OL412744) and rp (accession no. OL473789) sequences of the T. chinensis witches'-broom phytoplasma yielded 99.6% sequence identity with those of phytoplasmas of group 16SrV jujube witches'-broom (JWB) phytoplasma (accession no. CP025121 for 16S rRNA gene and AF396941 for rp gene). The 16S rRNA gene sequence of phytoplasma in host plant E. sylvestris (accession no. OM885990) is 99.7% similarity to the 'Elaeocarpus zollingeri' yellows phytoplasma (accession no. LC257960) and 99.4% similarity to the 'Elaeocarpus sylvestris' decline phytoplasma (accession no. MW553140), but 95.8% similarity to the 16S rRNA gene of phytoplasma in T. chinensis. The virtual RFLP tool, iPhyClassifier delineated the T. chinensis phytoplasma (accession no. OL412744) to group 16SrV-B (accession no. AB052876) with the similarity coefficient 1.0 (Fig 2), and phytoplasma in E. sylvestris to group 16Sr group XXXII with the similarity coefficient 0.97. Phylogeny analyses of 16S rRNA and rp genes (MEGA version 7.0.14, USA) using reference phytoplasmas from GenBank confirmed sequencing results and placed the T. chinensis phytoplasma in group 16SrV-B (Fig. 3 and 4). In China, the 16SrV-B phytoplasma group has been reported in Amaranthus retroflexus (Yang et al., 2011), Liriodendron chinense (Li et al., 2012), Prunus salicina (Gao et al., 2020) and sweet potato (Li et al., 2021). This is the first report of a 'Ca. Phytoplasma ziziphi', 16SrV-B related phytoplasma associated with parasitic T. chinensis in China. The results of this study indicate that T. chinensis could be a vector to spread phytoplasmas 16SrV group through parasitism and this can be helpful for related research.