Andrographolide promotes lymphangiogenesis and lymphatic vessel remodeling to alleviate secondary lymphedema.

Lymphedema, a prevalent, multifaceted, and chronic ailment, is mainly managed through physical manipulation and suffers from a lack of specific pharmacological treatments. Secondary lymphedema is mainly caused by impaired lymphatic drainage. Therapeutic lymphangiogenesis is a promising strategy in the treatment of lymphedema. Andrographolide, a natural product from Andrographis paniculata, is unknown whether andrographolide promotes lymphangiogenesis to improve secondary lymphedema. By using the murine tail lymphedema model, we demonstrated that andrographolide can reduce the thickness of subcutaneous tissue in the mice's tail and enhance lymphatic drainage. Moreover, immunofluorescence staining showed that the number of capillary lymphatic vessels in the ANDRO25 group was significantly more than that in the ANDRO50 and Model groups. Near-infrared lymphography images showed that highlighted sciatic lymph nodes could be seen in the ANDRO25 and ANDRO50 groups. In vitro, andrographolide could promote the proliferation and migration of LEC. In conclusion, andrographolide enhanced the recovery of lymphatic vessels, and promoted lymphatic drainage in the murine tail lymphedema model by promoting the proliferation of lymphatic endothelial cells, thereby reducing the symptoms of lymphedema. This suggested andrographolide may be used as a potential therapeutic drug or medical food ingredient to help patients with secondary lymphedema.

Spray Pyrolysis Regulated FeCo Alloy Anchoring on Nitrogen-Doped Carbon Hollow Spheres Boost the Performance of Zinc-Air Batteries.

Low-cost and high-efficiency non-precious metal-based oxygen reduction reaction (ORR)/oxygen evolution reaction (OER) bifunctional catalysts are the key to promoting the commercial application of metal-air batteries. Herein, a highly efficient catalyst of Fe0.18Co0.82 alloy anchoring on the nitrogen-doped porous carbon hollow sphere (FexCo1-x/N-C) is intelligently designed by spray pyrolysis (SP). The zinc in the SP-derived metal oxides and metal-organic framework volatilize at high temperature to construct a hierarchical porous structure with abundant defects and fully exposes the FeCo nanoparticles which uniformly anchor on the carbon substrate. In this structure, the coexistence of Fe0.18Co0.82 alloy and binary metal active sites (Fe-Nx/Co-Nx) guarantees the Fe0.2Co0.8/N-C catalyst exhibiting an excellent half-wave potential (E1/2 ═ 0.84 V) superior to 20% Pt/C for ORR and a suppressed overpotential (280 mV) than RuO2 for OER. Assembled rechargeable Zn-air battery (RZAB) demonstrates a promising specific capacity of 807.02 mAh g-1, peak power density of 159.08 mW cm-2 and durability without electrolyte circulation (550 h). This work proposes the design concept of utilizing an oxide core to in situ consume the porous carbon shell for anchoring metal active sites and construct defects, which benefits from spray pyrolysis in achieving precise control of the alloy structure and mass preparation.

A Tent-Inspired Portable Solar-Driven Water Purification Device for Wilderness Explorers.

Wilderness adventure favored by many enthusiasts often endanger lives due to lacking freshwater or drinking contaminated water. Therefore, compared to the inefficient methods of filtration, steaming, and direct solar heating, it is of great meaningfulness to develop a solar-driven water purification device with efficiency, lightweight, portability, and multi-water-quality purification by taking full advantage of solar-driven interfacial evaporation. Here, a tent-inspired portable solar-driven water purification device consisting of Janus-structured bacterial cellulose aerogel (JBCA) solar evaporator and tent-type condensation recovery device is reported. For the JBCA solar evaporator, it is prepared from biomass bacterial cellulose (BC) as raw material and hydroxylated carbon nanotubes (HCNT) as photothermal material, and the Janus property is achieved by the assistance of hydrophobic and hydrophilic chemical cross-linking. It exhibits lightweight, unibody, high photothermal conversion, efficient evaporation, and multi-water-quality purification capability for representative seawater, urine, and bacterial river water. For the tent-type condensation recovery device, it is based on the prototype of tent and uses flexible ultra-transparent polyvinyl chloride (PVC) film as raw material. Thanks to the rational prototype and material selection, it displays outstanding portability and lightweight through the folding/unfolding method. Therefore, the designed tent-inspired portable solar-driven water purification device demonstrates great potential application in wilderness exploration.

One-Step Synthesis of Multifunctional Bacterial Cellulose Film-Based Phase Change Materials with Cross-Linked Network Structure for Solar-Thermal Energy Conversion, Storage, and Utilization.

As one of the important directions of solar energy utilization, the construction of composite photothermal phase change materials (PCM) with reasonable network support and low leakage in the simple method is important to solve the transient availability of solar energy and achieve long-lasting energy output. Here, a multifunctional silylated bacterial cellulose (BC)/hydroxylated carbon nanotube (HCNT)/polyethylene glycol (PEG) (SBTP) photothermal film-based PCM with cross-linked network structure is prepared by simple one-step synthesis. The formation of the cross-linked network structure achieves the enhancement of BC support network, prominent dispersion of HCNT and the direct introduction and perfect interlocking of PEG. Therefore, the optimal SBTP film exhibits high thermal enthalpy of 145.1 J g-1, enthalpy efficiency of over 94%, robust shape stability and low leakage of <1.2%. It also displays high photothermal conversion of over 80 °C, photothermal storage of 394 s g-1 and excellent stability. Thus, it can demonstrate a maximum output voltage of 423 mV and high power density of 30.26 W m-2 under three solar irradiations when applied in the solar-thermal-electric energy conversion field. Meanwhile, it also can apply in the thermal management of solar cell and light-emitting diode (LED) chip, and convert the waste heat into electricity, demonstrating multi-scene application capability.

Scalable Dual In Situ Synthesis of Polyester Nanocomposites for High-Energy Storage.

Incorporating ultralow loading of nanoparticles into polymers has realized increases in dielectric constant and breakdown strength for excellent energy storage. However, there are still a series of tough issues to be dealt with, such as organic solvent uses, which face enormous challenges in scalable preparation. Here, a new strategy of dual in situ synthesis is proposed, namely polymerization of polyethylene terephthalate (PET) synchronizes with growth of calcium borate nanoparticles, making polyester nanocomposites from monomers directly. Importantly, this route is free of organic solvents and surface modification of nanoparticles, which is readily accessible to scalable synthesis of polyester nanocomposites. Meanwhile, uniform dispersion of as ultralow as 0.1 wt% nanoparticles and intense bonding at interfaces have been observed. Furthermore, the PET-based nanocomposite displays obvious increases in both dielectric constant and breakdown strength as compared to the neat PET. Its maximum discharged energy density reaches 15 J cm-3 at 690 MV m-1 and power density attains 218 MW cm-3 under 150 Ω resistance at 300 MV m-1, which is far superior to the current dielectric polymers that can be produced at large scales. This work presents a scalable, safe, low-cost, and environment-friendly route toward polymer nanocomposites with superior capacitive performance.

aenmd: annotating escape from nonsense-mediated decay for transcripts with protein-truncating variants.

SUMMARY: DNA changes that cause premature termination codons (PTCs) represent a large fraction of clinically relevant pathogenic genomic variation. Typically, PTCs induce transcript degradation by nonsense-mediated mRNA decay (NMD) and render such changes loss-of-function alleles. However, certain PTC-containing transcripts escape NMD and can exert dominant-negative or gain-of-function (DN/GOF) effects. Therefore, systematic identification of human PTC-causing variants and their susceptibility to NMD contributes to the investigation of the role of DN/GOF alleles in human disease. Here we present aenmd, a software for annotating PTC-containing transcript-variant pairs for predicted escape from NMD. aenmd is user-friendly and self-contained. It offers functionality not currently available in other methods and is based on established and experimentally validated rules for NMD escape; the software is designed to work at scale, and to integrate seamlessly with existing analysis workflows. We applied aenmd to variants in the gnomAD, Clinvar, and GWAS catalog databases and report the prevalence of human PTC-causing variants in these databases, and the subset of these variants that could exert DN/GOF effects via NMD escape. AVAILABILITY AND IMPLEMENTATION: aenmd is implemented in the R programming language. Code is available on GitHub as an R-package (github.com/kostkalab/aenmd.git), and as a containerized command-line interface (github.com/kostkalab/aenmd_cli.git).

Palladium-Catalyzed Multicomponent Carbonylation of Halides to Acylhydrazones.

The current methods for synthesizing acylhydrazones are limited by their multistep processes, narrow substrate scope, low selectivities, and poor yields. Herein, a fundamentally novel approach to bioactive acylhydrazones was developed based on the palladium-catalyzed multicomponent tandem condensation carbonylation of halides with aldehydes and hydrazines. This method provides a useful and efficient strategy for generating grams of various acylhydrazones in a one-pot manner. Mechanistic studies provided evidence of facile carbonylation of halides with the weak nucleophile hydrazones facilitated by a base.

Effects of Ultrasonic Power on the Structure and Rheological Properties of Skin Collagen from Albacore (Thunnus alalunga).

The effects of ultrasonic power (0, 150, 300, 450, and 600 W) on the extraction yield and the structure and rheological properties of pepsin-soluble collagen (PSC) from albacore skin were investigated. Compared with the conventional pepsin extraction method, ultrasonic treatment (UPSC) significantly increased the extraction yield of collagen from albacore skin, with a maximum increase of 8.56%. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that peptides of low molecular weight were produced when the ultrasonic power exceeded 300 W. Meanwhile, secondary structure, tertiary structure, and X-ray diffraction analyses showed that the original triple helix structure of collagen was intact after the ultrasonic treatment. The collagen solutions extracted under different ultrasonic powers had significant effects on the dynamic frequency sweep, but a steady shear test suggested that the collagen extracted at 150 W had the best viscosity. These results indicate that an ultrasonic power between 150 and 300 W can improve not only the extraction yield of natural collagen, but also the rheological properties of the collagen solution without compromising the triple helix structure.

EFFECT OF ANESTHESIA DURATION ON INTRAVITREAL INJECTION PAIN: A double-blinded, randomized, comparative study.

PURPOSE: To determine the effect of different durations of topical anesthesia on intravitreal injection (IVI) pain. METHODS: This was a double-blinded, randomized, comparative study . Three hundred and twelve sequential eyes undergoing IVI were randomized to one of six groups according to the duration of topical anesthesia (from 1 to 30 minutes, one group for every 5-minute range, Groups 1-6). Topical anesthesia before IVI was standardized. Patients graded their pain using the visual analog scale and the Wong-Baker FACES scale at 15 minutes after the procedure. RESULTS: The pain scores among the six groups were significantly different for the visual analog scale ( P = 0.013) and Wong-Baker FACES scale ( P = 0.024). The mean pain scores for Group 4 were 1.97 ± 1.04 (visual analog scale) and 2.02 ± 1.08 (Wong-Baker FACES scale) and were significantly lower than those of Group 1, 2, 5, or 6. CONCLUSION: The duration of topical anesthesia significantly correlated with IVI pain. Preoperative 0.5% proparacaine hydrochloride drops were most effective in relieving IVI pain 11 to 20 minutes after topical administration.

Metal-free photosensitized intermolecular carboimination of alkenes: a green and direct access to both ß-amino acids and ß-amino ketones.

ß-Amino carbonyl substructures are privileged motifs in natural products and active pharmaceutical compounds. Here, we report a photoinduced metal-free and highly regioselective intermolecular carboimination method via the simultaneous introduction of amino and carbonyl groups into the CC double bond in one step, providing straightforward, green and general access to both ß-amino acid and ß-amino ketone motifs from readily available alkene feedstocks. The mild reaction conditions, excellent functional group tolerance and product diversity should make this a broadly applicable carboimination approach of very broad interest to organic and medicinal chemists.

Identification of a Partial and Selective TRPV1 Agonist CPIPC for Alleviation of Inflammatory Pain.

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel, predominantly expressed in a subset of peripheral sensory neurons for pain signaling. Topical application of agonist capsaicin for desensitizing TRPV1 currents has been approved for relief of chronic pain. However, the potent TRPV1 capsaicin is not ingestible and even topical capsaicin causes common side effects such as skin irritation, swelling, erythema and pruritus, suggesting that a mild TRPV1 agonist might be helpful for reducing side effects while reliving pain. In this study, we reported on a partial and selective TRPV1 agonist 4-(5-chloropyridin-2-yl)-N-(1H-indazol-6-yl)piperazine-1-carboxamide named CPIPC that was modified based on targeting the residue Arg557, important for conversion between the channel antagonism and agonism. Whole-cell patch clamp recordings indicated a concentration-dependent activation of TRPV1 currents by CPIPC with an EC50 of 1.56 ± 0.13 µM. The maximum efficacy of CPIPC (30 µM) was about 60% of saturated capsaicin (10 µM). Repetitive additions of CPIPC caused TRPV1 current desensitization in both TRPV1-expressing HEK293 cells and dorsal root ganglion (DRG) sensory neurons. Oral administration of CPIPC dose-dependently alleviated inflammatory pain in mice. Further site-directed mutagenesis combined with molecular docking revealed that residue Arg557 is critical for TRPV1 activation by CPIPC. Taken together, we identified a novel partial and selective TRPV1 agonist CPIPC that exhibits antinociceptive activity in mice.

Establishing a new human hypertrophic cardiomyopathy-specific model using human embryonic stem cells.

Symptom of ventricular hypertrophy caused by cardiac troponin T (TNNT2) mutations is mild, while patients often showed high incidence of sudden cardiac death. The 92nd arginine to glutamine mutation (R92Q) of cTnT was one of the mutant hotspots in hypertrophic cardiomyopathy (HCM). However, there are no such human disease models yet. To solve this problem, we generated TNNT2 R92Q mutant hESC cell lines (heterozygote or homozygote) using TALEN mediated homologous recombination in this study. After directed cardiac differentiation, we found a relative larger cell size in both heterozygous and homozygous TNNT2 R92Q hESC-cardiomyocytes. Expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and sarcoplasmic reticulum Ca2+-ATPase2a (SERCA2a) were downregulated, while myocyte specific enhancer factor 2c (MEF2c) and the ratio of beta myosin to alpha myosin heavy chain (MYH7/MYH6) were increased in heterozygous TNNT2 R92Q hESC-cardiomyocytes. TNNT2 R92Q mutant cardiomyocytes exhibited efficient responses to heart-related pharmaceutical agents. We also found TNNT2 R92Q heterozygous mutant cardiomyocytes showed increased calcium sensitivity and contractility. Further, engineered heart tissues (EHTs) prepared by combining rat decellularized heart extracellular matrices with heterozygous R92Q mutant cardiomyocytes showed similar drug responses as to HCM patients and increased sensitivity to caspofungin-induced cardiotoxicity. Using RNA-sequencing of TNNT2 R92Q heterozygous mutant cardiomyocytes, we found dysregulation of calcium might participated in the early development of hypertrophy. Our hESC-derived TNNT2 R92Q mutant cardiomyocytes and EHTs are good in vitro human disease models for future disease studies and drug screening.

Distinct changes of in BTLA, ICOS, PD-1, and TIGIT expression on peripheral blood and decidual CD8+ T cells in women with unexplained recurrent spontaneous abortion†.

The two-way communication between the mother and the fetus is accomplished by immune cells. CD8+ T cells of normal pregnant (NP) women express progesterone receptor (PR). Binding of PR to progesterone (P) and the production of progesterone-induced blocking factor (PIBF) can aid immune escape, which is an important factor in the maternal immune response. We detected the proportion of CD8+ T cells and the expression of the surface costimulatory molecules BTLA, TIGIT, ICOS, and PD-1 in peripheral blood and decidual tissues of women with unexplained recurrent spontaneous abortion (URSA) and in NP women. All patients were at 8 -10 weeks of gestation. The results showed that there was no change in the proportions of CD8+ T cells in peripheral blood and decidual tissues of URSA patients compared to those of NP women. In peripheral blood, compared with the NP group, the URSA group showed decreased expression of BTLA + CD8+ T cells and the difference was statistically significant, but there was no difference between the groups in terms of TIGIT + CD8+, PD-1 + CD8+, and ICOS + CD8+ T cells. There was no change in the levels of TIGIT + CD8+, PD-1 + CD8+, ICOS + CD8+, and BTLA + CD8+ T cells in decidual tissue. These data confirm that the number of CD8+ T cells in peripheral blood and decidual tissue is not the main factor leading to the pathogenesis of URSA, and other immune cells may play an important role in URSA, but this hypothesis needs further exploration and research.

Avian Reticuloendotheliosis Viral Oncogene Related B Regulates Lymphatic Endothelial Cells during Vessel Maturation and Is Required for Lymphatic Vessel Function in Adult Mice.

NF-κB signals through canonical transcription factor p65 (RelA)/p50 and noncanonical avian reticuloendotheliosis viral oncogene related B (RelB)/p52 pathways. The RelA/p50 is involved in basal and inflammatory lymphangiogenesis. However, the role of RelB/p52 in lymphatic vessel biology is unknown. Herein, we investigated changes in lymphatic vessels (LVs) in mice deficient in noncanonical NF-κB signaling and the function of RelB in lymphatic endothelial cells (LECs). LVs were examined in Relb-/-, p52-/-, or control mice, and the gene expression profiles in LECs with RelB knockdown. Relb-/-, but not p52-/-, mice exhibited multiple LV abnormalities. They include the following: i) increased capillary vessel diameter, ii) reduced smooth muscle cell (SMC) coverage of mature vessels, iii) leakage, and iv) loss of active and passive lymphatic flow. Relb-/- mature LVs had thinner vessel walls, more apoptotic LECs and SMCs, and fewer LEC junctions. RelB knockdown LECs had decreased growth, survival, and adhesion, and dysregulated signaling pathways involving these cellular events. These results suggest that Relb-/- mice have abnormal LVs, mainly in mature vessels with reduced SMC coverage, leakage, and loss of contractions. RelB knockdown in LECs leads to reduced growth, survival, and adhesion. RelB plays a vital role in LEC-mediated LV maturation and function.

Urban-Rural Differences in Bone Mineral Density and its Association with Reproductive and Menstrual Factors Among Older Women.

PURPOSE: This study aimed to compare the bone mineral density (BMD) of older women living in rural and urban areas, and evaluate the potential factors affecting the risk of osteoporosis. METHODS: We recruited 574 women aged 65 years or older from rural areas and 496 from urban areas in Shanghai, China. The BMD values of the lumbar vertebrae and total left hip were measured by a dual energy X-ray absorptiometry densitometer. We also recorded information about education level, family income, medications, reproductive and menstrual history, diet, smoking, and alcohol consumption. RESULTS: Women in urban areas had significantly higher BMD in their lumbar spine, and there was a dramatic increase in the proportion of women with osteoporosis in rural areas. The age at menarche was significantly higher among women living in rural areas, and there were more years from menarche to menopause among urban women. Rural women had significantly higher numbers of both pregnancies and parity, and a significantly lower age at first parity. In multiple linear regression analyses, years from menarche to menopause was independently related to high lumbar spine BMD, while age at menarche and parity was independently related to low lumbar spine BMD. CONCLUSION: More older women in rural areas had osteoporosis. Later menarche, less years from menarche to menopause and higher parity might partially contribute to decreased BMD among women in rural areas. More attention should be paid to women in rural areas to prevent bone loss and further bone and health impairment.

Ginsenoside Rg1 promotes lymphatic drainage and improves chronic inflammatory arthritis.

OBJECTIVE: The lymphatic system plays an important role in joint diseases. This study aimed to evaluate the effects of ginsenoside Rg1 on lymphatic drainage and accumulation of inflammatory products in the joints. METHODS: Two-month-old transgenic mice that overexpress tumor necrosis factor alpha (TNF-α; TNF-Tg) were used as the animal models. Ginsenoside Rg1 was administered for 12 weeks and the lymphatic drainage in the mice was evaluated using near infrared-indocyanine green (NIR-ICG) lymphatic imaging system. The clinical symptoms of arthritis were evaluated weekly. The ankle and knee joints were harvested for hematoxylin-eosin (HE), alcian blue/orange G (ABOG), and tartrate-resistant acid phosphatase (TRAP) staining, and the foot dorsal skin was used for whole-mount immuno-staining. Simultaneously, the serum levels of IL-6 and TNF-α were detected using enzyme-linked immunosorbent assay (ELISA). RESULTS: Ginsenoside Rg1 significantly improved the lymphatic drainage function, reduced synovial inflammation and bone erosion, decreased serum IL-6 and TNF-α concentration, and increased smooth muscle coverage on the collecting lymphatic vessels in the foot skin of the TNF-Tg mice. Furthermore, ginsenoside Rg1 treatment for 12 weeks did not cause any damage to the liver and kidney tissues. CONCLUSION: Ginsenoside Rg1 improves lymphatic drainage and joint inflammation in TNF-Tg mice. Therefore, ginsenoside Rg1 has the potential to be a candidate drug for the treatment of inflammatory arthritis.

Establishment of a PRKAG2 cardiac syndrome disease model and mechanism study using human induced pluripotent stem cells.

PRKAG2 cardiac syndrome is a distinct form of human cardiomyopathy characterized by cardiac hypertrophy, ventricular pre-excitation and progressive cardiac conduction disorder. However, it remains unclear how mutations in the PRKAG2 gene give rise to such a complicated disease. To investigate the underlying molecular mechanisms, we generated disease-specific hiPSC-derived cardiomyocytes from two brothers both carrying a heterozygous missense mutation c.905G>A (R302Q) in the PRKAG2 gene and further corrected the R302Q mutation with CRISPR-Cas9 mediated genome editing. Disease-specific hiPSC-cardiomyocytes recapitulated many phenotypes of PRKAG2 cardiac syndrome including cellular enlargement, electrophysiological irregularities and glycogen storage. In addition, we found that the PRKAG2-R302Q mutation led to increased AMPK activities, resulting in extensive glycogen deposition and cardiomyocyte hypertrophy. Finally we confirmed that disrupted phenotypes of PRKAG2 cardiac syndrome caused by the specific PRKAG2-R302Q mutation can be alleviated by small molecules inhibiting AMPK activity and be rescued with CRISPR-Cas9 mediated genome correction. Our results showed that disease-specific hiPSC-CMs and genetically-corrected hiPSC-cardiomyocytes would be a very useful platform for understanding the pathogenesis of, and testing autologous cell-based therapies for, PRKAG2 cardiac syndrome.

Quantitative ¹H-NMR Spectroscopy for Profiling Primary Metabolites in Mulberry Leaves.

The primary metabolites in aqueous extract of mulberry (Morus alba L.) leaves were characterized by using proton nuclear magnetic resonance (¹H-NMR) spectroscopy. With the convenience of resonance assignment, GABA together with the other 10 primary metabolites was simultaneously identified and quantified in one ¹H-NMR spectrum. In this study, external calibration curves for metabolites were employed to calculate the concentrations of interests. The proposed quantitative approach was demonstrated with good linearity (r² ranged in the interval of 0.9965-0.9999), precision, repeatability, stability (RSD values in the ranges of 0.35-4.89%, 0.77-7.13% and 0.28-2.33%, respectively) and accuracy (recovery rates from 89.2% to 118.5%). The established ¹H-NMR method was then successfully applied to quantify 11 primary metabolites in mulberry leaves from different geographical regions within a rapid analysis time and a simple sample preparation procedure.

A subclass of HSP70s regulate development and abiotic stress responses in Arabidopsis thaliana.

Members of the HSP70 family function as molecular chaperones to maintain cellular homeostasis and help plants cope with environmental stimuli. However, due to functional redundancy and lack of effective chemical inhibitors, our knowledge of functions of individual HSP70s has remained limited. Here, we confirmed a subclass of HSP70s, including HSP70-1, -2, -3, -4, and -5, localized to the cytosol and nucleus in Arabidopsis thaliana. Histochemical analyses of promoter:GUS reporter lines showed that HSP70-1, -2, -3, and -4 genes were widely expressed, but HSP70-5 was not. In addition, individual HSP70 showed not only similar but also distinct transcriptions when treated by different abiotic stresses and phytohormones. No apparent phenotype was observed when individual HSP70 genes were overexpressed or knocked-out/down, but the double mutant hsp70-1 hsp70-4 and triple mutant hsp70-2 hsp70-4 hsp70-5 plants exhibited developmental phenotypes with shortened specific growth periods, curly and round leaves, twisted petioles, thin stems, and short siliques. Moreover, both mutants were hypersensitive to heat, cold, high glucose, salt and osmotic stress, but hyposensitive to abscisic acid. Genes related to flowering, and the cytokinin, brassinosteroid, and abscisic acid signaling pathways were differentially expressed in both mutants. Our studies suggest that, the individual HSP70 possibly performs both redundant and specific functions with the other members in the cytosolic/nuclear HSP70 subclass, and apart from enabling plants to cope with abiotic stresses, this subclass of cytosolic/nuclear HSP70 proteins also participates in diverse developmental processes and signaling pathways.

Genome-wide screen identifies signaling pathways that regulate autophagy during Caenorhabditis elegans development.

The mechanisms that coordinate the regulation of autophagy with developmental signaling during multicellular organism development remain largely unknown. Here, we show that impaired function of ribosomal protein RPL-43 causes an accumulation of SQST-1 aggregates in the larval intestine, which are removed upon autophagy induction. Using this model to screen for autophagy regulators, we identify 139 genes that promote autophagy activity upon inactivation. Various signaling pathways, including Sma/Mab TGF-ß signaling, lin-35/Rb signaling, the XBP-1-mediated ER stress response, and the ATFS-1-mediated mitochondrial stress response, regulate the expression of autophagy genes independently of the TFEB homolog HLH-30. Our study thus provides a framework for understanding the role of signaling pathways in regulating autophagy under physiological conditions.