Recent advances in discovery and biosynthesis of natural products from myxobacteria: an overview from 2017 to 2023.

Covering: 2017.01 to 2023.11Natural products biosynthesized by myxobacteria are appealing due to their sophisticated chemical skeletons, remarkable biological activities, and intriguing biosynthetic enzymology. This review aims to systematically summarize the advances in the discovery methods, new structures, and bioactivities of myxobacterial NPs reported in the period of 2017-2023. In addition, the peculiar biosynthetic pathways of several structural families are also highlighted.

Automated, multiparametric monitoring of respiratory biomarkers and vital signs in clinical and home settings for COVID-19 patients.

Capabilities in continuous monitoring of key physiological parameters of disease have never been more important than in the context of the global COVID-19 pandemic. Soft, skin-mounted electronics that incorporate high-bandwidth, miniaturized motion sensors enable digital, wireless measurements of mechanoacoustic (MA) signatures of both core vital signs (heart rate, respiratory rate, and temperature) and underexplored biomarkers (coughing count) with high fidelity and immunity to ambient noises. This paper summarizes an effort that integrates such MA sensors with a cloud data infrastructure and a set of analytics approaches based on digital filtering and convolutional neural networks for monitoring of COVID-19 infections in sick and healthy individuals in the hospital and the home. Unique features are in quantitative measurements of coughing and other vocal events, as indicators of both disease and infectiousness. Systematic imaging studies demonstrate correlations between the time and intensity of coughing, speaking, and laughing and the total droplet production, as an approximate indicator of the probability for disease spread. The sensors, deployed on COVID-19 patients along with healthy controls in both inpatient and home settings, record coughing frequency and intensity continuously, along with a collection of other biometrics. The results indicate a decaying trend of coughing frequency and intensity through the course of disease recovery, but with wide variations across patient populations. The methodology creates opportunities to study patterns in biometrics across individuals and among different demographic groups.

Constructing a Myxobacterial Natural Product Database to Facilitate NMR-Based Metabolomics Bioprospecting of Myxobacteria.

Myxobacteria are fascinating prokaryotes featuring a potent capacity for producing a wealth of bioactive molecules with intricate chemical topology as well as intriguing enzymology, and thus it is critical to developing an efficient pipeline for bioprospecting. Herein, we construct the database MyxoDB, the first public compendium solely dedicated to myxobacteria, which enabled us to provide an overview of the structural diversity and taxonomic distribution of known myxobacterial natural products. Moreover, we demonstrated that the cutting-edge NMR-based metabolomics was effective to differentiate the biosynthetic priority of myxobacteria, whereby MyxoDB could greatly streamline the dereplication of multifarious known compounds and accordingly speed up the discovery of new compounds. This led to the rapid identification of a class of linear di-lipopeptides (archangimins) and a rare rearranged sterol (corasterol) that were endowed with unique chemical architectures and/or biosynthetic enzymology. We also showcased that NMR-based metabolomics, MyxoDB, and genomics can also work concertedly to accelerate the targeted discovery of a polyketidic compound pyxipyrrolone C. All in all, this study sets the stage for the discovery of many more novel natural products from underexplored myxobacterial resources.

High-yield production of FK228 and new derivatives in a Burkholderia chassis.

FK228 (romidepsin) is the only natural histone deacetylases (HDACs) inhibitor approved by FDA to treat cutaneous and peripheral T-cell lymphoma. However, the limited supply and severe cardiotoxicity of FK228 underscore the importance to develop an effective synthetic biology platform for the manufacturing and fine-tuning of this drug lead. In this work, we constructed a Burkholderia chassis for the high-yield production of FK228-family (unnatural) natural products. By virtue of the optimized Burkholderia-specific recombineering system, the biosynthetic gene cluster (BGC) encoding the FK228-like skeleton thailandepsins (tdp) in Burkholderia thailandensis E264 was replaced with an attB integration site to afford the basal chassis KOGC1. The tdp BGC directly captured from E264 was hybridized with the FK228-encoding BGC (dep) using the versatile Red/ET technology. The hybrid BGC (tdp-dep) was integrated into the attB site of KOGC1, resulting in the heterologous expression of FK228. Remarkably, the titer reached 581 mg/L, which is 30-fold higher than that of native producer Chromobacterium violaceum No. 968. This success encouraged us to further engineer the NRPS modules 4 or 6 of hybrid tdp-dep BGC by domain units swapping strategy, and eight new FK228 derivatives (1-8) varying in the composition of amino acids were generated. Especially, the titers of 2 and 3 in KOGC1 were up to 985 mg/L and 453 mg/L, respectively. 2 and 3 displayed stronger cytotoxic activity than FK228. All in all, this work established a robust platform to produce FK228 and its new derivatives in sufficient quantities for anticancer drug development.

Discovery and Biosynthesis of Glycosylated Cycloheximide from a Millipede-Associated Actinomycete.

Chemical redundancy of microbial natural products (NPs) underscores the importance to exploit new resources of microorganisms. Insect-associated microbes are prolific but largely underexplored sources of diverse NPs. Herein, we discovered the new compound α-l-rhamnosyl-actiphenol (1) from a millipede-associated Streptomyces sp. ML6, which is the first glycosylated cycloheximide-class natural product. Interestingly, bioinformatics analysis of the ML6 genome revealed that the biosynthesis of 1 involves a cooperation between two gene clusters (chx and rml) located distantly on the genome of ML6. We also carried out in vitro enzymatic glycosylation of cycloheximide using an exotic promiscuous glycosyltransferase BsGT-1, which resulted in the production of an additional cycloheximide glycoside cycloheximide 7-O-ß-d-glucoside (5). Although the antifungal and cytotoxic activities of the new compounds 1 and 5 were attenuated relative to those of cycloheximide, our work not only enriches the chemical repertoire of the cycloheximide family but also provides new insights into the structure-activity relationship optimization and ecological roles of cycloheximide.

A wireless, skin-interfaced biosensor for cerebral hemodynamic monitoring in pediatric care.

The standard of clinical care in many pediatric and neonatal neurocritical care units involves continuous monitoring of cerebral hemodynamics using hard-wired devices that physically adhere to the skin and connect to base stations that commonly mount on an adjacent wall or stand. Risks of iatrogenic skin injuries associated with adhesives that bond such systems to the skin and entanglements of the patients and/or the healthcare professionals with the wires can impede clinical procedures and natural movements that are critical to the care, development, and recovery of pediatric patients. This paper presents a wireless, miniaturized, and mechanically soft, flexible device that supports measurements quantitatively comparable to existing clinical standards. The system features a multiphotodiode array and pair of light-emitting diodes for simultaneous monitoring of systemic and cerebral hemodynamics, with ability to measure cerebral oxygenation, heart rate, peripheral oxygenation, and potentially cerebral pulse pressure and vascular tone, through the utilization of multiwavelength reflectance-mode photoplethysmography and functional near-infrared spectroscopy. Monte Carlo optical simulations define the tissue-probing depths for source-detector distances and operating wavelengths of these systems using magnetic resonance images of the head of a representative pediatric patient to define the relevant geometries. Clinical studies on pediatric subjects with and without congenital central hypoventilation syndrome validate the feasibility for using this system in operating hospitals and define its advantages relative to established technologies. This platform has the potential to substantially enhance the quality of pediatric care across a wide range of conditions and use scenarios, not only in advanced hospital settings but also in clinics of lower- and middle-income countries.

Intramuscular Microvascular Flow Sensing for Flap Monitoring in a Porcine Model of Arterial and Venous Occlusion.

BACKGROUND: Commercially available near infrared spectroscopy devices for continuous free flap tissue oxygenation (StO2) monitoring can only be used on flaps with a cutaneous component. Additionally, differences in skin quality and pigmentation may alter StO2 measurements. Here, we present a novel implantable heat convection probe that measures microvascular blood flow for peripheral monitoring of free flaps, and is not subject to the same issues that limit the clinical utility of near-infrared spectroscopy. METHODS: The intratissue microvascular flow-sensing device includes a resistive heater, 4 thermistors, a small battery, and a Bluetooth chip, which allows connection to a smart device. Convection of applied heat is measured and mathematically transformed into a measurement of blood flow velocity. This was tested alongside Vioptix T.Ox in a porcine rectus abdominis myocutaneous flap model of arterial and venous occlusion. After flap elevation, the thermal device was deployed intramuscularly, and the cutaneous T.Ox device was applied. Acland clamps were alternately applied to the flap artery and veins to achieve 15 minutes periods of flap ischemia and congestion with a 15 minutes intervening recovery period. In total, five devices were tested in three flaps in three separate pigs over 16 vaso-occlusive events. RESULTS: Flow measurements were responsive to both ischemia and congestion, and returned to baseline during recovery periods. Flow measurements corresponded closely with measured StO2. Cross-correlation at zero lag showed agreement between these two sensing modalities. Two novel devices tested simultaneously on the same flap showed only minor variations in flow measurements. CONCLUSION: This novel probe is capable of detecting changes in tissue microcirculatory blood flow. This device performed well in a swine model of flap ischemia and congestion, and shows promise as a potentially useful clinical tool. Future studies will investigate performance in fasciocutaneous flaps and characterize longevity of the device over a period of several days.

Intramuscular Near-Infrared Spectroscopy for Muscle Flap Monitoring in a Porcine Model.

BACKGROUND: Current near-infrared spectroscopy (NIRS)-based systems for continuous flap monitoring are limited to flaps which carry a cutaneous paddle. As such, this useful and reliable technology has not previously been applicable to muscle-only free flaps where other modalities with substantial limitations continue to be utilized. METHODS: We present the first NIRS probe which allows continuous monitoring of local tissue oxygen saturation (StO2) directly within the substance of muscle tissue. This probe is flexible, subcentimeter in scale, waterproof, biocompatible, and is fitted with resorbable barbs which facilitate temporary autostabilization followed by easy atraumatic removal. This novel device was compared with a ViOptix T.Ox monitor in a porcine rectus abdominus myocutaneous flap model of arterial and venous occlusions. During these experiments, the T.Ox device was affixed to the skin paddle, while the novel probe was within the muscle component of the same flap. RESULTS: The intramuscular NIRS device and skin-mounted ViOptix T.Ox devices produced very similar StO2 tracings throughout the vascular clamping events, with obvious and parallel changes occurring upon vascular clamping and release. The normalized cross-correlation at zero lag describing correspondence between the novel intramuscular NIRS and T.Ox devices was >0.99. CONCLUSION: This novel intramuscular NIRS probe offers continuous monitoring of oxygen saturation within muscle flaps. This experiment demonstrates the potential suitability of this intramuscular NIRS probe for the task of muscle-only free flap monitoring, where NIRS has not previously been applicable. Testing in the clinical environment is necessary to assess durability and reliability.

A Wireless Near-Infrared Spectroscopy Device for Flap Monitoring: Proof of Concept in a Porcine Musculocutaneous Flap Model.

BACKGROUND: Current near-infrared spectroscopy (NIRS)-based systems for continuous flap monitoring are highly sensitive for detecting malperfusion. However, the clinical utility and user experience are limited by the wired connection between the sensor and bedside console. This wire leads to instability of the flap-sensor interface and may cause false alarms. METHODS: We present a novel wearable wireless NIRS sensor for continuous fasciocutaneous free flap monitoring. This waterproof silicone-encapsulated Bluetooth-enabled device contains two light-emitting diodes and two photodetectors in addition to a battery sufficient for 5 days of uninterrupted function. This novel device was compared with a ViOptix T.Ox monitor in a porcine rectus abdominus myocutaneous flap model of arterial and venous occlusions. RESULTS: Devices were tested in four flaps using three animals. Both devices produced very similar tissue oxygen saturation (StO2) tracings throughout the vascular clamping events, with obvious and parallel changes occurring on arterial clamping, arterial release, venous clamping, and venous release. Small interdevice variations in absolute StO2 value readings and magnitude of change were observed. The normalized cross-correlation at zero lag describing correspondence between the novel NIRS and T.Ox devices was >0.99 in each trial. CONCLUSION: The wireless NIRS flap monitor is capable of detecting StO2 changes resultant from arterial vascular occlusive events. In this porcine flap model, the functionality of this novel sensor closely mirrored that of the T.Ox wired platform. This device is waterproof, highly adhesive, skin conforming, and has sufficient battery life to function for 5 days. Clinical testing is necessary to determine if this wireless functionality translates into fewer false-positive alarms and a better user experience.

The Discovery and Biosynthesis of Nicotinic Myxochelins from an Archangium sp. SDU34.

Myxobacteria are a prolific source of structurally diverse natural products, and one of the best-studied myxobacterial products is the siderophore myxochelin. Herein, we report two new compounds, myxochelins N (1) and O (2), that are nicotinic paralogs of myxochelin A, from the terrestrial myxobacterium Archangium sp. SDU34; 2 is functionalized with a rare 2-oxazolidinone. A precursor-feeding experiment implied that the biosynthesis of 1 or 2 was due to altered substrate specificity of the loading module of MxcE, which likely accepts nicotinic acid and benzoic acid instead of more conventional 2,3-dihydroxybenzoic acid. We also employed a phylogenomic approach to map the evolutionary relationships of the myxochelin biosynthetic gene clusters (BGCs) in all the available myxobacterial genomes, to pave the way for the future discovery of potentially hidden myxochelin derivatives. Although the biological function of 1 and 2 is unclear yet, this work underpins that even extensively studied BGCs in myxobacteria can still produce new chemistry.

Merging the Versatile Functionalities of Boronic Acid with Peptides.

Peptides inherently feature the favorable properties of being easily synthesized, water-soluble, biocompatible, and typically non-toxic. Thus, boronic acid has been widely integrated with peptides with the goal of discovering peptide ligands with novel biological activities, and this effort has led to broad applications. Taking the integration between boronic acid and peptide as a starting point, we provide an overview of the latest research advances and highlight the versatile and robust functionalities of boronic acid. In this review, we summarize the diverse applications of peptide boronic acids in medicinal chemistry and chemical biology, including the identification of covalent reversible enzyme inhibitors, recognition, and detection of glycans on proteins or cancer cell surface, delivery of siRNAs, development of pH responsive devices, and recognition of RNA or bacterial surfaces. Additionally, we discuss boronic acid-mediated peptide cyclization and peptide modifications, as well as the facile chemical synthesis of peptide boronic acids, which paved the way for developing a growing number of peptide boronic acids.

Myxadazoles, Myxobacterium-Derived Isoxazole-Benzimidazole Hybrids with Cardiovascular Activities.

There is a continuous need for novel microbial natural products to fill the drying-up drug development pipeline. Herein, we report myxadazoles from Myxococcus sp. SDU36, a family of novel chimeric small molecules that consist of N-ribityl 5,6-dimethylbenzimidazole and a linear fatty acid chain endowed with an isoxazole ring. The experiments of genome sequencing, gene insertion mutation, isotope labelling, and precursor feeding demonstrated that the fatty acid chain was encoded by a non-canonical PKS/NRPS gene cluster, whereas the origin of N-ribityl 5,6-dimethylbenzimidazole was related to the vitamin B12 metabolism. The convergence of these two distinct biosynthetic pathways through a C-N coupling led to the unique chemical framework of myxadazoles, which is an unprecedented hybridization mode in the paradigm of natural products. Myxadazoles exhibited potent vasculogenesis promotion effect and moderate antithrombotic activity, underscoring their potential usage for the treatment of cardiovascular diseases.

Effects of glycosylation on the bioactivity of rapamycin.

The macrolactone rapamycin (RAP) presents a broad range of bioactivities, but its clinical applications are compromised due to the poor water solubility and low bioavailability, which could probably be overcome by glycosylation. In this study, we tested a set of promiscuous glycosyltransferases (GTs) to modify rapamycin with four different sugar donors. BsGT-1 displayed the best glycosylation activity with a preference for UDP-glucose, and the glycosylation happened at C-28 or C-40 of rapamycin, producing rapamycin-40-O-ß-D-glucoside (RG1), and two new compounds rapamycin-28-O-ß-D-glucoside (RG2) and rapamycin-28,40-O-ß-D-diglucoside (RG3). The glycosylation remarkably improved water solubility and almost completely abolished cytotoxicity but simultaneously attenuated the antifungal, antitumor, and immunosuppression bioactivities of rapamycin. We found the glycosylation at C-40 had less effect on the bioactivities than that at C-28. The molecular docking analysis revealed that the glycosylation, especially the glycosylation at C-28, weakened the hydrophobic and hydrogen bonding contacts between the rapamycin glucosides and the binding proteins: the FK506-binding protein (FKBP12) and the FKBP12-rapamycin binding (FRB) domain. This study highlights a succinct approach to expand the chemical diversity of the therapeutically important molecule rapamycin by using promiscuous glycosyltransferases. Moreover, the fact that glycosyl moieties at different positions of rapamycin affect bioactivity to different extents inspires further glycosylation engineering to improve properties of rapamycin. KEY POINTS: • Rapamycin was glycosylated efficiently by some promiscuous GTs. • Glycosylation improved water solubility, attenuated cytotoxicity, and bioactivities. • Glycosylation affected the interactions between ligand and binding proteins.

Eleven healthy live births: a result of simultaneous preimplantation genetic testing of α- and ß-double thalassemia and aneuploidy screening.

PURPOSE: To evaluate the efficacy of preimplantation genetic testing (PGT) for α- and ß-double thalassemia combined with aneuploidy screening using next-generation sequencing (NGS). METHODS: An NGS-based PGT protocol was performed between 2017 and 2018 for twelve couples, each of which carried both α- and ß-thalassemia mutations. Trophectoderm biopsy samples underwent whole-genome amplification using multiple displacement amplification (MDA), followed by NGS for thalassemia detection and aneuploidy screening. A selection of several informative single nucleotide polymorphisms (SNPs) established haplotypes. Aneuploidy screening was performed only on unaffected noncarriers and carriers. Unaffected and euploid embryos were transferred into the uterus through frozen-thawed embryo transfer (FET). RESULTS: A total of 280 oocytes were retrieved following 18 ovum pick-up (OPU) cycles, with 182 normally fertilized and 112 cultured to become blastocysts. One hundred and seven (95.5%, 107/112) blastocysts received conclusive PGT results, showing 56 (52.3%, 56/107) were unaffected. Thirty-seven (66.1%, 37/56) of the unaffected were also identified as euploid. One family had no transferable embryos. Unaffected and euploid embryos were then transferred into the uterus of the other 11 couples resulting in 11 healthy live births. The clinical pregnancy rate was 61.1% (11/18) per OPU and 68.8% (11/16) per FET, with no miscarriage reported. Seven families accepted the prenatal diagnosis and received consistent results with the NGS-based PGT. CONCLUSION: This study indicated that NGS could realize the simultaneous PGT of double thalassemia and aneuploidy screening in a reliable and accurate manner. Moreover, it eliminated the need for multiple biopsies, alleviating the potential damages to the pre-implanted blastocysts.

Cadasides, Calcium-Dependent Acidic Lipopeptides from the Soil Metagenome That Are Active against Multidrug-Resistant Bacteria.

The growing threat of antibiotic resistance necessitates the discovery of antibiotics that are active against resistant pathogens. Calcium-dependent antibiotics are a small family of structurally diverse acidic lipopeptides assembled by nonribosomal peptide synthetases (NRPSs) that are known to display various modes of action against antibiotic-resistant pathogens. Here we use NRPS adenylation (AD) domain sequencing to guide the identification, recovery, and cloning of the cde biosynthetic gene cluster from a soil metagenome. Heterologous expression of the cde biosynthetic gene cluster led to the production of cadasides A (1) and B (2), a subfamily of acidic lipopeptides that is distinct from previously characterized calcium-dependent antibiotics in terms of both overall structure and acidic residue rich peptide core. The cadasides inhibit the growth of multidrug-resistant Gram-positive pathogens by disrupting cell wall biosynthesis in the presence of high concentrations of calcium. Interestingly, sequencing of AD domains from diverse soils revealed that sequences predicted to arise from cadaside-like gene clusters are predominantly found in soils containing high levels of calcium carbonate.

Discovery of novel glycerolated quinazolinones from Streptomyces sp. MBT27.

Actinobacteria are a major source of novel bioactive natural products. A challenge in the screening of these microorganisms lies in finding the favorable growth conditions for secondary metabolite production and dereplication of known molecules. Here, we report that Streptomyces sp. MBT27 produces 4-quinazolinone alkaloids in response to elevated levels of glycerol, whereby quinazolinones A (1) and B (2) form a new sub-class of this interesting family of natural products. Global Natural Product Social molecular networking (GNPS) resulted in a quinazolinone-related network that included anthranilic acid (3), anthranilamide (4), 4(3H)-quinazolinone (5), and 2,2-dimethyl-1,2-dihydroquinazolin-4(3H)-one (6). Actinomycins D (7) and X2 (8) were also identified in the extracts of Streptomyces sp. MBT27. The induction of quinazolinone production by glycerol combined with biosynthetic insights provide evidence that glycerol is integrated into the chemical scaffold. The unprecedented 1,4-dioxepane ring, that is spiro-fused into the quinazolinone backbone, is most likely formed by intermolecular etherification of two units of glycerol. Our work underlines the importance of varying the growth conditions for the discovery of novel natural products and for understanding their biosynthesis.

Lugdunomycin, an Angucycline-Derived Molecule with Unprecedented Chemical Architecture.

The angucyclines form the largest family of polycyclic aromatic polyketides, and have been studied extensively. Herein, we report the discovery of lugdunomycin, an angucycline-derived polyketide, produced by Streptomyces species QL37. Lugdunomycin has unique structural characteristics, including a heptacyclic ring system, a spiroatom, two all-carbon stereocenters, and a benzaza-[4,3,3]propellane motif. Considering the structural novelty, we propose that lugdunomycin represents a novel subclass of aromatic polyketides. Metabolomics, combined with MS-based molecular networking analysis of Streptomyces sp. QL37, elucidated 24 other rearranged and non-rearranged angucyclines, 11 of which were previously undescribed. A biosynthetic route for the lugdunomycin and limamycins is also proposed. This work demonstrates that revisiting well-known compound families and their producer strains still is a promising approach for drug discovery.

Type 2 diabetes increases oocyte mtDNA mutations which are eliminated in the offspring by bottleneck effect.

BACKGROUND: Diabetes induces many complications including reduced fertility and low oocyte quality, but whether it causes increased mtDNA mutations is unknown. METHODS: We generated a T2D mouse model by using high-fat-diet (HFD) and Streptozotocin (STZ) injection. We examined mtDNA mutations in oocytes of diabetic mice by high-throughput sequencing techniques. RESULTS: T2D mice showed glucose intolerance, insulin resistance, low fecundity compared to the control group. T2D oocytes showed increased mtDNA mutation sites and mutation numbers compared to the control counterparts. mtDNA mutation examination in F1 mice showed that the mitochondrial bottleneck could eliminate mtDNA mutations. CONCLUSIONS: T2D mice have increased mtDNA mutation sites and mtDNA mutation numbers in oocytes compared to the counterparts, while these adverse effects can be eliminated by the bottleneck effect in their offspring. This is the first study using a small number of oocytes to examine mtDNA mutations in diabetic mothers and offspring.

Simultaneously Enhancing Light Emission and Suppressing Efficiency Droop in GaN Microwire-Based Ultraviolet Light-Emitting Diode by the Piezo-Phototronic Effect.

Achievement of p-n homojuncted GaN enables the birth of III-nitride light emitters. Owing to the wurtzite-structure of GaN, piezoelectric polarization charges present at the interface can effectively control/tune the optoelectric behaviors of local charge-carriers (i.e., the piezo-phototronic effect). Here, we demonstrate the significantly enhanced light-output efficiency and suppressed efficiency droop in GaN microwire (MW)-based p-n junction ultraviolet light-emitting diode (UV LED) by the piezo-phototronic effect. By applying a -0.12% static compressive strain perpendicular to the p-n junction interface, the relative external quantum efficiency of the LED is enhanced by over 600%. Furthermore, efficiency droop is markedly reduced from 46.6% to 7.5% and corresponding droop onset current density shifts from 10 to 26.7 A cm-2. Enhanced electrons confinement and improved holes injection efficiency by the piezo-phototronic effect are revealed and theoretically confirmed as the physical mechanisms. This study offers an unconventional path to develop high efficiency, strong brightness and high power III-nitride light sources.

Silicon Nanowire/Polymer Hybrid Solar Cell-Supercapacitor: A Self-Charging Power Unit with a Total Efficiency of 10.5.

An integrated self-charging power unit, combining a hybrid silicon nanowire/polymer heterojunction solar cell with a polypyrrole-based supercapacitor, has been demonstrated to simultaneously harvest solar energy and store it. By efficiency enhancement of the hybrid nanowire solar cells and a dual-functional titanium film serving as conjunct electrode of the solar cell and supercapacitor, the integrated system is able to yield a total photoelectric conversion to storage efficiency of 10.5%, which is the record value in all the integrated solar energy conversion and storage system. This system may not only serve as a buffer that diminishes the solar power fluctuations from light intensity, but also pave its way toward cost-effective high efficiency self-charging power unit. Finally, an integrated device based on ultrathin Si substrate is demonstrated to expand its feasibility and potential application in flexible energy conversion and storage devices.