Maximizing Electrostatic Interaction in Ultramicroporous Metal-Organic Frameworks for the One-Step Purification of Acetylene from Ternary Mixture.

Developing efficient adsorbents for acetylene purification from multicomponent mixtures is of critical significance in the chemical industry, but the trade-off between regenerability and selectivity significantly restricts practical industrial applications. Here, we report ultramicroporous metal-organic frameworks with acetylene-affinity channels to enhance electrostatic interaction between C2H2 and frameworks for the efficient one-step purification of C2H2 from C2H2/CO2/C2H4 mixtures, in which the electrostatic interaction led to high regenerability. The obtained SNNU-277 exhibits significantly higher adsorption capacity for C2H2 than that for both C2H4 and CO2 at 298 K and 0.1 bar, while an ultrahigh selectivity of C2H2/C2H4 (100.6 at 298 K) and C2H2/CO2 (32.8 at 298 K) were achieved at 1 bar. Breakthrough experiments validated that SNNU-277 can efficiently separate C2H2 from C2H2/C2H4/CO2 mixtures. CO2 and C2H4 broke through the adsorption column at 4 and 14.8 min g-1, whereas C2H2 was detected until 177.6 min g-1 at 298 K. Theoretical calculations suggest that the framework is electrostatically compatible with C2H2 and electrostatically repels C2H4 and CO2 in the mixed components. This work highlights the importance of rational pore engineering for maximizing the electrostatic effect with the preferentially absorbed guest molecule for efficient multicomponent separation.

Pore Environmental Modification by Alkoxy Groups in Pore-Space-Partitioned Metal-Organic Frameworks to Achieve Gas Uptake-Selectivity Balance.

Due to the trade-off barrier between high storage capacity and high selectivity, the controllable and systematic design of metal-organic frameworks (MOFs) aiming at performance optimization is still challenging. Herein, considering the effectiveness of alkoxy group functionalization and a pore-space partition strategy, a series of rigid Mg-pacs-MOFs (SNNU-10-n, n = 1-6) with flexible side chains are built for the first time, realizing systematic pore environmental modification. The steric hindrance effects, electron-donating ability, and the flexibility of alkoxy groups are considered as key factors, which lead to a regular change of gas adsorption capacity and selectivity. Notably, methoxy-modified SNNU-10-1 with moderately high storage capacities of C2H2 (139.4 cm3 g-1), C2H4 (100.4 cm3 g-1), CO2 (105.0 cm3 g-1), and high selectivity values for equimolar C2H2/CH4 (431.8), C2H4/CH4 (164.2), and CO2/CH4 (16.1) mixture separation at 273 K and 100 kPa achieves an ideal gas uptake-selectivity balance. Breakthrough experiments verified that it could effectively separate the above-mentioned mixtures under ambient conditions, and GCMC simulation provides a deep understanding of methoxy group functionalization. Undoubtedly, this work not only realizes controllable regulation of gas adsorption behavior but also proves the validity of improving selectivity by alkoxy groups in those platforms with high gas-uptake potential to overcome the trade-off barrier.

The complete mitochondrial genome of Ogmocotyle ailuri: gene content, composition and rearrangement and phylogenetic implications.

Trematodes of the genus Ogmocotyle are intestinal flukes that can infect a variety of definitive hosts, resulting in significant economic losses worldwide. However, there are few studies on molecular data of these trematodes. In this study, the mitochondrial (mt) genome of Ogmocotyle ailuri isolated from red panda (Ailurus fulgens) was determined and compared with those from Pronocephalata to investigate the mt genome content, genetic distance, gene rearrangements and phylogeny. The complete mt genome of O. ailuri is a typical closed circular molecule of 14 642 base pairs, comprising 12 protein-coding genes (PCGs), 22 transfer RNA genes, 2 ribosomal RNA genes and 2 non-coding regions. All genes are transcribed in the same direction. In addition, 23 intergenic spacers and 2 locations with gene overlaps were determined. Sequence identities and sliding window analysis indicated that cox1 is the most conserved gene among 12 PCGs in O. ailuri mt genome. The sequenced mt genomes of the 48 Plagiorchiida trematodes showed 5 types of gene arrangement based on all mt genome genes, with the gene arrangement of O. ailuri being type I. Phylogenetic analysis using concatenated amino acid sequences of 12 PCGs revealed that O. ailuri was closer to Ogmocotyle sikae than to Notocotylus intestinalis. These data enhance the Ogmocotyle mt genome database and provide molecular resources for further studies of Pronocephalata taxonomy, population genetics and systematics.

De-Linker-Enabled Exceptional Volumetric Acetylene Storage Capacity and Benchmark C2 H2 /C2 H4 and C2 H2 /CO2 Separations in Metal-Organic Frameworks.

An ideal adsorbent for separation requires optimizing both storage capacity and selectivity, but maximizing both or achieving a desired balance remain challenging. Herein, a de-linker strategy is proposed to address this issue for metal-organic frameworks (MOFs). Broadly speaking, the de-linker idea targets a class of materials that may be viewed as being intermediate between zeolites and MOFs. Its feasibility is shown here by a series of ultra-microporous MOFs (SNNU-98-M, M=Mn, Co, Ni, Zn). SNNU-98 exhibit high volumetric C2 H2 uptake capacity under low and ambient pressures (175.3 cm3 cm-3 @ 0.1 bar, 222.9 cm3 cm-3 @ 1 bar, 298 K), as well as extraordinary selectivity (2405.7 for C2 H2 /C2 H4 , 22.7 for C2 H2 /CO2 ). Remarkably, SNNU-98-Mn can efficiently separate C2 H2 from C2 H2 /CO2 and C2 H2 /C2 H4 mixtures with a benchmark C2 H2 /C2 H4 (1/99) breakthrough time of 2325 min g-1 , and produce 99.9999 % C2 H4 with a productivity up to 64.6 mmol g-1 , surpassing values of reported MOF adsorbents.

Precise Introduction of Single Vanadium Site into Indium-Organic Framework for CO2 Capture and Photocatalytic Fixation.

The capture and fixation of CO2 under mild conditions is a cost-effective route to reduce greenhouse gases, but it is challenging because of the low conversion and selectivity issues. Metal-organic frameworks (MOFs) are promising in the fields of adsorption and catalysis because of their structural tunability and variability. However, the precise structural design of MOFs is always pursued and elusive. In this work, a metal-mixed MOF (SNNU-97-InV) was designed by precisely introducing single vanadium site into the isostructural In-MOF (SNNU-97-In). The single V sites clearly change the interactions between the MOF framework and CO2 molecules, leading to a 71.3% improvement in the CO2 adsorption capacity. At the same time, the enhanced light absorption enables SNNU-97-InV to efficiently convert CO2 into cyclic carbonates (CCs) with epoxides under illumination. Controlled experiments showed that the promoted performance of SNNU-97-InV may be that the V═O site can more easily combine with CO2 and convert them into an intermediate state under illumination, and the possible mechanism was thus speculated.

Amide-Functionalized Metal-Organic Frameworks Coupled with Open Fe/Sc Sites for Efficient Acetylene Purification.

Acetylene (C2H2) purification is of great importance for many chemical synthesis and processes. Metal-organic frameworks (MOFs) are widely used for gas adsorption and separation due to their variable structure and porosity. However, the exploitation of ideal MOF adsorbents for C2H2 keeps a challenging task. Herein, a combination of open metal sites (OMSs) and Lewis basic sites (LBSs) in robust MOFs is demonstrated to effectively promote the C2H2 purification performance. Accordingly, SNNU-37(Fe/Sc), two isostructural MOFs constituted by [Fe3O(COO)6] or [Sc3O(COO)6] trinuclear clusters and amide-functionalized tricarboxylate linkers, were designed with extra-stable 3,6-connected new architectures. Derived from the coexistence of high-density OMSs and LBSs, the C2H2 adsorption amounts of SNNU-37(Fe/Sc) are much higher than those values for C2H4 and CO2. Theoretical IAST selectivity values of SNNU-37(Fe) are 2.4 for C2H2/C2H4 (50/50, v/v) and 9.9 for C2H2/CO2 (50/50, v/v) at 298 K and 1 bar, indicating an excellent C2H2 separation ability. Experimental breakthrough curves also revealed that SNNU-37(Fe) could effectively separate C2H2/C2H4 and C2H2/CO2 under ambient conditions. GCMC simulations further indicate that open Fe or Sc sites and amide groups mainly contribute to stronger adsorption sites for C2H2 molecules.

[Improved effects of saponins from Panax japonicus on decline of cognitive function in natural aging rats via NLRP3 inflammasome pathway].

The aim of this paper was to investigate the effect of total saponins from Panax japonicus( SPJ) on cognitive decline of natural aging rats and its mechanism. Thirty male SD rats of eighteen month old were randomly divided into three groups: aged group,10 mg·kg~(-1) SPJ-treated group and 30 mg·kg~(-1) SPJ-treated group. The SPJ-treated groups were given SPJ at the dosages of 10 mg·kg~(-1) and 30 mg·kg~(-1),respectively,from the age of 18 to 24 months. Aged group were lavaged the same amount of saline,10 six-month-old rats were used as control group,with 10 rats in each group. The open field test,novel object recognition and Morris water maze were performed to detect the changes of cognitive function in each group. The changes of synaptic transmission of long-term potentiation( LTP) in hippocampal CA1 region were detected by field potential recording. Western blot was used to detect the protein levels of NLRP3,ASC,caspase-1 and the changes of Glu A1,Glu A2,CAMKⅡ,CREB and phosphorylation of CAMKⅡ,CREB in each group.The results showed that SPJ could improve the decline of cognitive function in aging rats,reduce the damage of LTP in the hippocampal CA1 region of aged rats,and decrease the expression of NLRP3,ASC,caspase-1 in aging rats. At the same time,SPJ could enhance the membrane expression of AMPA receptor( Glu A1 and Glu A2),and increase the expression of p-CAMKⅡand p-CREB in aging rats.SPJ could improve cognitive decline of natural aging rats,and its mechanism may be related to regulating NLRP3 inflammasome,thus regulating the membrane expression of AMPA receptor,and enhancing the expression phosphorylation of CAMKⅡ and CREB.

[Ribozyme riboswitch based gene expression regulation systems for gene therapy applications: progress and challenges].

Robust and efficient control of therapeutic gene expression is needed for timing and dosing of gene therapy drugs in clinical applications. Ribozyme riboswitch provides a promising building block for ligand-controlled gene-regulatory system, based on its property that exhibits tunable gene regulation, design modularity, and target specificity. Ribozyme riboswitch can be used in various gene delivery vectors. In recent years, there have been breakthroughs in extending ribozyme riboswitch's application from gene-expression control to cellular function and fate control. High throughput screening platforms were established, that allow not only rapid optimization of ribozyme riboswitch in a microbial host, but also straightforward transfer of selected devices exhibiting desired activities to mammalian cell lines in a predictable manner. Mathematical models were employed successfully to explore the performance of ribozyme riboswitch quantitively and its rational design predictably. However, to progress toward gene therapy relevant applications, both precision rational design of regulatory circuits and the biocompatibility of regulatory ligand are still of crucial importance.

Colonoscopy-assisted removal of an impaction foreign body at the rectosigmoid junction: A case report.

BACKGROUND: When an anorectal foreign body is found, its composition and shape should be evaluated, and a timely and effective treatment plan should be developed based on the patient's symptoms to avoid serious complications such as intestinal perforation caused by displacement of the foreign body. CASE SUMMARY: A 54-year-old male was admitted to our outpatient clinic on June 3, 2023, due to a rectal foreign body that had been embedded for more than 24 h. The patient reported using a glass electrode tube to assist in the recovery of prolapsed hemorrhoids, however, the electrode tube was inadvertently inserted into the anus and could not be removed by the patient. During hospitalization, the patient underwent surgery, and the foreign body was dragged into the rectum with the aid of colonoscopy. The anus was dilated with a comb-type pulling hook and an anal fistula pulling hook to widen the anus and remove the foreign body, and the local anal symptoms were then relieved with topical drugs. The patient was allowed to eat and drink, and an entire abdominal Computed tomography (CT) and colonoscopy were reviewed 3 d after surgery. CT revealed no foreign body residue and colonoscopy showed no metal or other residues in the colon and rectum, and no apparent intestinal tract damage. CONCLUSION: The timeliness and rationality of the surgical and therapeutic options for this patient were based on a literature review of the clinical signs and conceivable conditions in such cases. The type, material and the potential risks of rectal foreign bodies should be considered.

Prevalence and Molecular Characterization of Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi in Cattle in Heilongjiang Province, Northeast China.

Crytosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi are important diarrheal pathogens with a global distribution that threatens the health of humans and animals. Despite cattle being potential transmission hosts of these protozoans, the associated risks to public health have been neglected. In the present study, a total of 1155 cattle fecal samples were collected from 13 administrative regions of Heilongjiang Province. The prevalence of Cryptosporidium spp., G. duodenalis, and E. bieneusi were 5.5% (64/1155; 95% CI: 4.2-6.9), 3.8% (44/1155; 95% CI: 2.7-4.9), and 6.5% (75/1155; 95% CI: 5.1-7.9), respectively. Among these positive fecal samples, five Cryptosporidium species (C. andersoni, C. bovis, C. ryanae, C. parvum, and C. occultus), two G. duodenalis assemblages (E and A), and eight E. bieneusi genotypes (BEB4, BEB6, BEB8, J, I, CHS7, CHS8, and COS-I) were identified. Phylogenetic analysis showed that all eight genotypes of E. bieneusi identified in the present study belonged to group 2. It is worth noting that some species/genotypes of these intestinal protozoans are zoonotic, suggesting a risk of zoonotic disease transmission in endemic areas. The findings expanded our understanding of the genetic composition and zoonotic potential of Cryptosporidium spp., G. duodenalis, and E. bieneusi in cattle in Heilongjiang Province.

[Effects of Heavy Metal Pollution on the Structure of Microbial Communities in Different Habitats].

Heavy metal pollution seriously threatens the diversity and composition of microbial communities in various ecosystems. However, little is known about the effects of heavy metal pollution on the structure of microbial communities in the three habitats of "surface water-sediment-groundwater." Here, with help of 16S rRNA high-throughput sequencing technology, the diversity and composition of microbial communities, as well as the underlying controlling factors, were investigated and compared among the surface water, sediment, and groundwater of the Tanghe sewage reservoir. The results showed significant differences in the diversity of microbial communities among different habitats, with the highest α diversity observed in groundwater rather than surface water or sediment. Meanwhile, microbial communities also displayed distinct compositions among the three different habitats. Specifically, Pedobacter, Hydrogenophaga, Flavobacterium, and Algoriphagus were dominant in surface water; metal-tolerant bacteria such as Ornatilinea, Longilinea, Thermomarinilinea, and Bellilinea prevailedin sediment; and Arthrobacter, Gallionella, and Thiothrix were abundant in groundwater. Furthermore, physicochemical factors and metal variables jointly determined the microbial community structure in the three habitats. Among the influencing factors,pH, NO3--N, and Li were the main factors affecting the microbial structure in surface water; TP, NH4+-N, Cr, Fe, Cu, and Zn significantly impacted microorganisms in sediment; and only pH (not metal pollutants) was weakly associated with the microbial composition in groundwater. Overall, heavy metal pollution significantly shaped the microbial community structure in sediment, followed by that in surface water and groundwater. These results provide important scientific guidance for the ecological restoration and the sustainable development of heavy metal-polluted ecosystems.

[Composition Structure and Influence Factors of Bacterial Communities in the Miyun Reservoir].

As the largest reservoir in North China, the Miyun Reservoir is the most important surface drinking water source in Beijing. Bacteria are key regulators of reservoir ecosystem structure and function, and exploring the community distribution characteristics of bacteria is important for maintaining water quality safety in reservoirs. The spatiotemporal distribution and environmental factors of bacterial communities in the water and sediment of the Miyun Reservoir were explored using the high-throughput sequencing method. The results showed a higher α-diversity and non-significant seasonal variation of the bacterial community in the sediment, and the abundant sedimental species were affiliated with Proteobacteria. For planktonic bacteria, Actinobacteriota was the dominant phylum, and the seasonal variance was represented by CL500-29_marine_group and hgcI_clade in the wet season and Cyanobium_PCC-6307 in the dry season. Additionally, obvious differences in key species were also found in water and sediment, and more indicator species were obtained in sedimental bacteria. Further, a more complex co-existence network was identified in water compared to that in sediment, indicating the strong ability of planktonic bacteria to resist environmental changes. Environmental factors had a significantly higher effect on the bacterial community of the water column than that of the sediment. Furthermore, SO2-4 and TN were the main factors affecting planktonic bacteria and sedimental bacteria, respectively. These findings revealed the distribution patterns and driving forces of the bacterial community in the Miyun Reservoir, which will provide important guidance for reservoir management and water-quality assurance.

Application of the first rechargeable sacral neuromodulation system for treatment of neurogenic lower urinary tract dysfunction in China: a case report.

Neurogenic lower urinary tract dysfunction (NLUTD) is caused by nervous system lesions and characterized by impaired micturition and urinary incontinence. The goal of treatment is to manage these symptoms, improve quality of life, prevent urinary tract infections, and maintain urinary function. Pelvic floor muscle training and medication are commonly used for treating it. Sacral neuromodulation (SNM) has been used in the treatment of NLUTD for >20 years worldwide, and its effectiveness and safety have been verified. Several countries have begun using a rechargeable SNM system, whereas the current sacral SNM system used in China is non-rechargeable. A 29-year-old man with persistent voiding dysfunction for >20 years presented with progressive symptoms 1 year ago. He was admitted to our hospital in August 2022 for a rechargeable SNM system implantation. The patient underwent a video-urodynamic examination and the Short Form of a Urinary Quality of Life Questionnaire (SF-Qualiveen) before and 1 month after surgery. The video-urodynamic examination showed that the maximum bladder capacity significantly increased after surgery, bladder compliance improved, the phenomenon of uninhibited bladder contraction during filling decreased, and urine leakage was reduced. The SF-Qualiveen score showed the patient's quality of life significantly improved. To our knowledge, this is the first case of a rechargeable SNM system implantation in China, which shows that it is safe and effective. More clinical cases and long-term observation are still needed. In conclusion, a rechargeable SNM system has significance for health and the economy and has a broad clinical application prospect.

Targeted Drug Delivery Systems for Curcumin in Breast Cancer Therapy.

Breast cancer (BC) is the most prevalent type of cancer in the world and the main reason women die from cancer. Due to the significant side effects of conventional treatments such as chemotherapy and radiotherapy, the search for supplemental and alternative natural drugs with lower toxicity and side effects is of interest to researchers. Curcumin (CUR) is a natural polyphenol extracted from turmeric. Numerous studies have demonstrated that CUR is an effective anticancer drug that works by modifying different intracellular signaling pathways. CUR's therapeutic utility is severely constrained by its short half-life in vivo, low water solubility, poor stability, quick metabolism, low oral bioavailability, and potential for gastrointestinal discomfort with high oral doses. One of the most practical solutions to the aforementioned issues is the development of targeted drug delivery systems (TDDSs) based on nanomaterials. To improve drug targeting and efficacy and to serve as a reference for the development and use of CUR TDDSs in the clinical setting, this review describes the physicochemical properties and bioavailability of CUR and its mechanism of action on BC, with emphasis on recent studies on TDDSs for BC in combination with CUR, including passive TDDSs, active TDDSs and physicochemical TDDSs.

Rare rectal gastrointestinal stromal tumor case: A case report and review of the literature.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are rare tumors of the gastrointestinal tract accounting for less than 1% of all gut tumors. GISTs occurring in the rectum are extremely rare, and these usually present at an advanced stage compared with other sites. CASE SUMMARY: A 60-year-old male who presented with features of sensations of rectal tenesmus was referred to our department with a mass in the lower rectum that was detected during a routine checkup. Colonoscopy, transrectal ultrasound, perianal magnetic resonance imaging and ultrasonic contrast were used to diagnose the rectum GIST, and then the patient underwent complete transanal resection using the ultrasonic scalpel. The patient was discharged ten days after the operation and was defined as low risk. Therefore, he had no need to receive subsequent adjuvant therapies, and he had not suffered any anal dysfunction or had any evidence of recurrence at follow up. CONCLUSION: Surgical resection with histologically negative margins is the standard curative treatment for rectal GISTs. Appropriate surgical techniques based on the location, size, and resectability of the tumor should attract great attention from clinicians.

Transcriptomic and metabolomic studies on the protective effect of molecular hydrogen against nuclear electromagnetic pulse-induced brain damage.

Background: Excessive doses of electromagnetic radiation pose a negative impact on the central nervous system and lead to mental disorders. Molecular hydrogen can scavenge intracellular hydroxyl radicals, acting as an antioxidant, anti-apoptotic and anti-inflammatory agent. We seek to assess the capability of molecular hydrogen to ameliorate brain damage induced by electromagnetic radiation. Methods: NEMP (nuclear electromagnetic pulse), a subset of electromagnetic pulse with high voltage value that could cause severe brain injury, was applied to this study. Male wild-type rats were divided into four groups: the control group, the H2 (Molecular hydrogen) group, the NEMP group and the NEMP+H2 group. Rats in the H2 group and the NEMP+H2 group were fed with saturated hydrogen-rich water from 3 days before NEMP exposure (electromagnetic field intensity 400 kV/m, rising edge 20 ns and pulse width 200 ns) to the day of sacrifice. One day after exposure, animal behavior experiments were performed, and samples for transcriptomics and metabolomics analysis were collected. Seven days after exposure, histopathological experiments were conducted. Results: The data from the elevated plus maze and the open field test showed that NEMP exposure elicited anxiety-like behavior in rats, which could be alleviated by H2 treatment. Histopathological results manifested that NEMP exposure-induced injuries of the neurons in the hippocampus and amygdala could be attenuated by H2 treatment. Transcriptomic results revealed that NEMP exposure had a profound effect on microtubule structure in the brain. And the combined analysis of transcriptomics and metabolomics showed that H2 has a significant impact on the neuroactive ligand-receptor interaction, synaptic vesicle cycle and synapse etc. Moreover, it was indicated that the glutathione metabolic pathway played a vital role in the NEMP exposure-induced damage and the protective activity of H2. Conclusions: H2 is identified as a potent agent against NEMP exposure-induced brain damage and has the potential to be a promising electromagnetic radiation protectant.

[Changes of biomechanical properties of soft tissues in underwater corpse for postmortem interval estimation].

OBJECTIVE: To explore the postmortem changes of biomechanical properties of underwater corpses and value for estimating postmortem interval. METHODS: SD rats were sacrificed by cervical vertebra dislocation and stored in the water at constant temperature. The vessel wall, skin, muscle, small intestine and colon were sampled at different postmortem time points (0h, 6h, 12h, 18h, 24h, 30h, 36h, 42h, 48h, 60h, 72h, 96h, 120h, 144h, 168h, 192h). The biomechanics properties of different soft tissues including ultimate load, strain, maximum stress were measured by electronic universal material testing machine. RESULTS: Except for the vessel wall, the biomechanics properties of skin, muscle, small intestine and colon showed linear decrease gradually after death. Each tissue displayed its obvious "window period" for PMI estimation. CONCLUSION: The time-sequential changes of biomechanical property parameters of soft tissue in underwater corpses are significantly correlated with PMI and it could be a simple and quantitive new technology for estimating PMI. The specific heat capacity of the heat-eliminating medium around the corpses probably is one of the physical factors to influence algor mortis, autolysis, putrefaction and biomechanics properties.

Application of nanoindentation technology in testing the mechanical properties of skull materials.

Three-point bending test, compression test and tensile test can detect the mechanical properties of the whole layer of skull, but cannot detect the mechanical properties of the inner plate, the diploe and the outer plate of the skull. In this study, nanoindentation technology was applied to detect mechanical properties of micro-materials of the skull, and differences in micro-mechanical properties of the inner, diploe and outer plates of the skull and cranial suture of human carcasses at different ages were analyzed. The differences in hardness (HIT) and modulus of elasticity (E) were statistically significant among different age groups (P < 0.01). In terms of structure, the E of diploe was higher than that of other structures, while HIT had no significant statistical difference. In terms of location, both HIT and E showed that left frontal (LF) was significantly higher than coronal suture (CS). The above results were consistent with the multi-factor ANOVAs. In addition, the multi-factor ANOVAs further explained the interaction of HIT and E with age, location and structure. It was believed that the nanoindentation technique could be used to analyze laws of micromechanical properties of different structures of human cadaveric skull and cranial suture.

Intestine-specific removal of DAF-2 nearly doubles lifespan in Caenorhabditis elegans with little fitness cost.

Twenty-nine years following the breakthrough discovery that a single-gene mutation of daf-2 doubles Caenorhabditis elegans lifespan, it remains unclear where this insulin/IGF-1 receptor gene is expressed and where it acts to regulate ageing. Using knock-in fluorescent reporters, we determined that daf-2 and its downstream transcription factor daf-16 are expressed ubiquitously. Using tissue-specific targeted protein degradation, we determined that intracellular DAF-2-to-DAF-16 signaling in the intestine plays a major role in lifespan regulation, while that in the hypodermis, neurons, and germline plays a minor role. Notably, intestine-specific loss of DAF-2 activates DAF-16 in and outside the intestine, causes almost no adverse effects on development and reproduction, and extends lifespan by 94% in a way that partly requires non-intestinal DAF-16. Consistent with intestine supplying nutrients to the entire body, evidence from this and other studies suggests that altered metabolism, particularly down-regulation of protein and RNA synthesis, mediates longevity by reduction of insulin/IGF-1 signaling.