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Leveraging the specificity of antibody to deliver cytotoxic agent into tumor, antibody-drug conjugates (ADCs) have become one of the hotspots in the development of anticancer therapies. Although significant progress has been achieved, there remain challenges to overcome, including limited penetration into solid tumors and potential immunogenicity. Fully human single-domain antibodies (UdAbs), with their small size and human nature, represent a promising approach for addressing these challenges. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a glycosylated cell surface protein that rarely expressed in normal adult tissues but overexpressed in diverse cancers, taking part in tumorigenesis, progression, and metastasis. In this study, we investigated the therapeutic potential of UdADC targeting CEACAM5. We performed biopanning in our library and obtained an antibody candidate B9, which bound potently and specifically to CEACAM5 protein (KD= 4.84 nM) and possessed excellent biophysical properties (low aggregation tendency, high homogeneity, and thermal stability). The conjugation of B9 with a potent cytotoxic agent, monomethyl auristatin E (MMAE), exhibited superior antitumor efficacy against CEACAM5-expressing human gastric cancer cell line MKN-45, human pancreatic carcinoma cell line BxPC-3 and human colorectal cancer cell line LS174T with IC50values of 38.14, 25.60, and 101.4 nM, respectively. In BxPC-3 and MKN-45 xenograft mice, administration of UdADC B9-MMAE (5 mg/kg, i.v.) every 2 days for 4 times markedly inhibited the tumor growth without significant change in body weight. This study may have significant implications for the design of next-generation ADCs.

Phage display technology allows for rapid selection of antibodies from the large repertoire of human antibody fragments displayed on phages. However, antibody fragments should be converted to IgG for biological characterizations and affinity of antibodies obtained from phage display library is frequently not sufficient for efficient use in clinical settings. Here, we describe a new approach that combines phage and mammalian cell display, enabling simultaneous affinity screening of full-length IgG antibodies. Using this strategy, we successfully obtained a novel germline-like anti-TIM-3 monoclonal antibody named m101, which was revealed to be a potent anti-TIM-3 therapeutic monoclonal antibody via in vitro and in vivo experiments, indicating its effectiveness and power. Thus, this platform can help develop new monoclonal antibody therapeutics with high affinity and low immunogenicity.

Digitoflavone (DG) is a natural flavonoid abundant in many fruits, vegetables, and medicinal plants. We investigated whether DG inhibits lipid accumulation and inflammatory responses in alcoholic liver disease (ALD) in vivo and in vitro. The mouse ALD model was established by chronically feeding male C57BL/6 mice an ethanol-containing Lieber-DeCarli liquid diet. In vitro, mouse peritoneal macrophages (MPMs) and mouse bone marrow-derived macrophages (BMDMs) were stimulated with LPS/ATP, whereas HepG2 cells and mouse primary hepatocytes were treated with ethanol. DG reduced the serum levels of transaminase and serum and hepatic levels of triglycerides and malondialdehyde in ALD mice. DG downregulated SREBP1 and its target genes and upregulated PPARα and its target genes in the liver of mice with ALD. DG inhibited TLR4-mediated NLRP3 inflammasome activation, consequently reversing the inflammatory response, including the production of HMGB1, IL-1β, and IL-36γ, as well as the infiltration of macrophages and neutrophils. DG blocked NLRP3/ASC/caspase-1 inflammasome activation and HMGB1 release in LPS/ATP-stimulated MPMs. When Tlr4was knocked in LPS/ATP-stimulated BMDMs, HMGB1 production and release were blocked, and NLRP3-mediated cleavage and release of IL-1β was suppressed in Hmgb1-silenced BMDMs. DG amplified these inhibitory effects in Tlr4or Hmgb1knockdown BMDMs. In ethanol-exposed hepatocytes, DG reduced lipogenesis and promoted lipid oxidation by inhibiting the HMGB1-TLR4 signaling pathway while suppressing the inflammatory response induced by ethanol exposure. Our data demonstrated that DG inhibited the occurrence of lipid accumulation and the inflammatory response via the HMGB1-TLR4 axis, underscoring a promising approach and utility of DG for the treatment of ALD.

Tissue kallikrein has protective function against various types of injury. In this study, we investigated whether exogenous pancreatic kininogenase (PK) conferred renoprotection in a rat model of unilateral ureteral obstruction (UUO) and H2O2-treated HK-2 cells in vitro. SD rats were subjected to UUO surgery, then PK (7.2?U/g per day, ip) was administered for 7 or 14 days. After the treatment, rats were euthanized; the obstructed kidneys were harvested for further examination. We found that PK administration significantly attenuated interstitial inflammation and fibrosis, and downregulated the expression of proinflammatory (MCP-1, TLR-2, and OPN) and profibrotic (TGF-ß1 and CTGF) cytokines in obstructed kidney. UUO-induced oxidative stress, closely associated with excessive apoptotic cell death and autophagy via PI3K/AKT/FoxO1a signaling, which were abolished by PK administration. We further showed that PK administration increased the expression of bradykinin receptors 1 and 2 (B1R and B2R) mRNA and the production of NO and cAMP in kidney tissues. Coadministration with either B1R antagonist (des-Arg9-[Leu8]-bradykinin) or B2R antagonist (icatibant) abrogated the renoprotective effects of PK, and reduced the levels of NO and cAMP in obstructed kidney. In H2O2-treated HK-2 cells, addition of PK (6?pg/mL) significantly decreased ROS production, regulated the expression of oxidant and antioxidant enzymes, suppressed the expression of TGF-ß1 and MCP-1, and inhibited cell apoptosis. Our data demonstrate that PKtreatment protects against the progression of renal fibrosis in obstructed kidneys.

Ginseng has been used as a functional food and tonic for enhancing immune power. Here, the potential protective effect of 20S-protopanaxatriol (M4), the metabolite of protopanaxatriol, against hepatic fibrosis is investigated, which could provide nutritional interventions for disease treatment. M4 could inhibit extracellular matrix (ECM) deposition and reduce the levels of proinflammatory cytokines such as caspase 1, interleukin 1 β (IL-1β), interleukin 1 receptor type 1 (IL1R1), and interleukin 6 (IL-6). M4 also significantly increased the expression of farnesoid X receptor (FXR), suppressed the purinergic ligand-gated ion channel 7 receptor (P2X7r) signaling pathway, and works as an FXR agonist, GW4064. In thioacetamide (TAA)-induced mice, M4 could attenuate the histopathological changes and significantly regulate the expression levels of FXR and P2X7r. M4 ameliorated TAA-induced hepatic fibrosis due to the reduction of P2X7r secretion, inhibition of hepatic stellate cell (HSCs) activation, and inflammation, which were all associated with FXR activation. Hence, M4 might be useful a nutritional preventive approach in antihepatic fibrosis and antihepatic inflammation.

Hepatic fibrosis is a compensatory response to chronic liver injury and inflammation, and dietary intervention is recommended as one of the fundamental prevention strategies. Raspberry ketone (RK) is an aromatic compound first isolated from raspberry and widely used to prepare food flavors. The current study investigated the hepatoprotection and potential mechanism of RK against hepatic fibrosis. In vitro, hepatic stellate cell (HSC) activation was stimulated with TGF-β and cultured with RK, farnesoid X receptor (FXR), or peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) agonist or inhibitor, respectively. In vivo, C57BL/6 mice were injected intraperitoneally with thioacetamide (TAA) at 100/200 mg/kg from the first to the fifth week. Mice were intragastrically administrated with RK or Cur once a day from the second to the fifth week. In activated HSCs, RK inhibited extracellular matrix (ECM) accumulation, inflammation, and epithelial–mesenchymal transition (EMT) process. RK both activated FXR/PGC-1α and regulated their crosstalk, which were verified by their inhibitors and agonists. Deficiency of FXR or PGC-1α also attenuated the effect of RK on the reverse of activated HSCs. RK also decreased serum ALT/AST levels, liver histopathological change, ECM accumulation, inflammation, and EMT in mice caused by TAA. Double activation of FXR/PGC-1α might be the key targets for RK against hepatic fibrosis. Above all, these discoveries supported the potential of RK as a novel candidate for the dietary intervention of hepatic fibrosis.

Pleurotus citrinopileatus(golden oyster mushroom) is a widely used edible mushroom. We investigated the inhibitory effect of P. citrinopileatusaqueous extract against alcoholic steatohepatitis and its underlying mechanism. Acute and chronic ethanol-feeding murine models were established by intragastrically administering ethanol or feeding an ethanol-containing Lieber–DeCarli liquid diet to male C57BL/6 mice. In both models, P. citrinopileatusdecreased serum alanine aminotransferase (ALT), aspartate transaminase (AST), triglyceride (TG), and hepatic TG levels. Hematoxylin and eosin (HE) and Oil Red O staining confirmed that P. citrinopileatusameliorated both acute and chronic alcoholic hepatosteatosis, characterized by regulation of lipid-metabolism-related proteins, including sirtuin 1 (SIRT1), AMP-activated kinase (AMPK), and sterol regulatory element-binding protein (SREBP1). P. citrinopileatusreversed inflammatory response via modulating purinergic receptor P2X ligand-gated ion channel 7 (P2X7R)-NOD-like receptor pyrin domain 3 (NLRP3) inflammasome. P. citrinopileatusrestored the expressions of those proteins to a normal level. In addition, HepG2 cells were incubated with P. citrinopileatusprior to ethanol stimulation. P. citrinopileatusreduced ethanol exposure-induced lipid deposition. Concomitantly, P. citrinopileatusincreased AMPK and SIRT1 expressions, which were reduced by ethanol treatment. P. citrinopileatusameliorated alcoholic hepatic steatosis and accompanied inflammatory response via regulating SIRT1–AMPK and P2X7R–NLRP3 inflammasome activation, highlighting a promising strategy and utility of P. citrinopileatusfor alcoholic steatohepatitis as dietary health supplements.

Ginseng is widely used in energy drinks, dietary supplements, and herbal medicines, and its pharmacological actions are related with energy metabolism. As an important modulating energy metabolism pathway, liver X receptors (LXRs) can promote the resolving of hepatic fibrosis and inflammation. The present study aims to evaluate the regulation of 25-OCH3-PPD, a ginsenoside isolated from Panax ginseng, against hepatic fibrosis and inflammation in thioacetamide (TAA)-stimulated mice by activating the LXRs pathway. 25-OCH3-PPD decreases serum ALT/AST levels and improves the histological pathology of liver in TAA-induced mice; attenuates transcripts of pro-fibrogenic markers associated with hepatic stellate cell activation; attenuates the levels of pro-Inflammatory cytokines and blocks apoptosis happened in liver; inhibits NLRP3 inflammasome by affecting P2X7R activation; and regulates PI3K/Akt and LKB1/AMPK-SIRT1. 25-OCH3-PPD also facilitates LX25Rs and FXR activities decreased by TAA stimulation. 25-OCH3-PPD also decreases α-SMA via regulation of LXRs and P2X7R-NLRP3 in vitro. Our data suggest the possibility that 25-OCH3-PPD promotes activity of LXRs to ameliorate P2X7R-mediated NLRP3 inflammasome in the development of hepatic fibrosis.

Kidney tumor is one of the common malignant tumors of urinary system. However, rapid and accurate segmentation of kidney tissue is still a challenging problem in the medical image processing field on account of its obscure onset and uncertain and discontinuous boundary of its anatomical structure. We proposed a deep learning method globa-local UNet11 (GL-UNet11) for ultrasonic image segmentation of kidney, renal parenchyma and renal sinus, aiming at the inaccuracy of internal and marginal segmentation in ultrasonic image segmentation.

Medical ultrasound image classification based on convolutional neural network is the mainstream breast cancer classification model, but its limited perceptual ability limits its ability to obtain global information.

Telomeric DNA of human chromosomes plays a significant role in physiological processes such as cell cycle, aging, cancer and genetic stability due to its special sequence and structure. The research on small molecule ligands targeting G-quadruplex formed by such special sequence has attracted considerable attention, and has achieved great breakthrough. In this paper, we summarize the DNA sequences and structures of three kinds of typical human telomeric G-quadruplex, providing an important reference for further research.

DNA G-quadruplex (G4-DNA) has emerged as a new drug target for anti-tumor. The small compounds can induce the formation of G4-DNA and stabilize its structures, which is of potential significance for the tumor treatment. This paper focuses on our current understanding about the structure of G4-DNA, the binding mode between G4-DNA and small molecular ligands, and natural products targeting G4-DNA.

Objective: To monitor the induction of apoptosis in HT-29 cells by three compounds of oxazinone derivatives (A-C) with similar structures and research the mechanism of those oxazinone derivatives in induction of apoptosis in HT-29 cells. Methods: HT-29 cells were used for the determination of cytotoxicity elicited by oxazinone compounds. Cytotoxic effects of these compounds in HT-29 cells are monitored by a Real-Time Cell Analyser system. Results: All the oxazinone derivatives exhibited growth inhibition in HT-29 cells in a concentration-dependent manner. Conclusion: All the three compounds of oxazinone derivatives (A-C) could exhibit growth inhibition in HT-29 cells in a dose-dependent manner.

Over the past years, synthesis of pyrrole-imidazole (Py-Im) polyamides has been achieved by solution-phase and solid-phase methods. Comparing with solution-phase synthesis, the solid-phase synthesis has showed great superiority in various aspects. The solid-phase synthesis is a rapid, effective, energy-saving and environment-friendly method, which has been widely used in the synthesis of pyrrole-imidazole polyamides. Many complicated polyamides can be obtained quickly and effectively through this method. By far, the application of the solid-phase synthesis for Py-Im polyamides has made rapid development. Resin as the main carrier, a key substance in solid phase synthesis, consists of two parts: polymer (macromolecular resin) and linking chain (linker). To date, there are many kinds of resins applied in the solid phase synthesis, such as PAM resin, Wang resin, Oxime resin and Clear resin, and so on. In this article, we will focus on the elaboration about the basic principle and application of the four kinds of resins mentioned above in solid-phase synthesis of polyamides. This provides an important reference for development of polyamides.

Thermal performance calculation is the core task of designing power station boiler. By abstracting generalized components and generalized fluid nodes, and defining the process unit and process section at the logic level, the universal physical model of boiler was built in a particular form of flowsheet. Meanwhile, a sequential modular approach was proposed as the main algorithm for boiler thermal calculation based on process system steady-state simulation theory. Two key problems in the algorithm, i.e., module calculations and the logics of calling the modules calculations were explained. Finally, a practically developed system BESS, which has excellent flexibility and extensibility was presented. It turns out that the model and algorithm can be successfully employed in developing the general-purpose software for boiler thermal calculation.

Tri-sectional regenerative air heater is used widely because of its compactness and better performance. Study on the matching analytical calculation method of heat transfer is rarely carried out because of the complicated heat transfer process. This paper developed a model to solve the heat transfer calculation of multi-sectional regenerative air heaters, which usually have several layers. Then we designed the computational procedure to carry out the model. One example of a tri-sectional regenerative air heater with hot layer and cold layer shows the effectiveness of the algorithm, and the results suggest that this approach is valid. The impact of leakage on performance of the regenerative air heater was discussed. There is a negative linear correlation between exhaust gas temperature and air leakage, and boiler efficiency has a nearly linear negative correlation with air leakage.

In mice, there has been increasing evidence that FOXP3-expressing CD4+CD25+ regulatory T cells (Tregs) inhibit potentially reactive T cells to allo-antigens and play an important role in transplant (Tx) tolerance. Human CD4+CD25 high+ T cells represent Tregs, characterized by anergic and antigen-specific suppressive properties. Despite the significance of miniature swine as a preclinical model, only limited data are available regarding the existence of a porcine counterpart to the murine or human Tregs. Methods: From peripheral blood of five adult miniature swine, CD4+ cells (CD4+), CD4+CD25 high+ cells (CD25high+), CD4+CD25low+ cells (CD25low+), and CD4+CD25- cells (CD25-) were isolated with a cell sorter. Expression of the homologous gene to murine FOXP3 was quantified by RT-PCR in isolated fractions, and normalized to GAPDH. Proliferation of CD25high+ and suppressive property of CD25high+ to CD4+ responder cells upon allogeneic stimulation was evaluated by MLR and dilution assay, respectively, after isolation and 9-day culture with allogeneic cells in the presence of IL-2. Results: FOXP3 was expressed ten times higher in CD25 high+, compared to that in CD25low+ (p<0.05). CD25- expressed almost no FOXP3. CD25high+ was anergic and could suppress the proliferation of responder CD4+ upon allogeneic stimulation after isolation. After culture, CD25high+ remained anergic and showed a more suppressive effect on cells used for culture than on third party cells. Conclusions: 1) CD25high+ in miniature swine peripheral blood expressed an extremely high level of FOXP3. 2) This fraction was anergic and has suppressive properties, showing antigen-specificity after exposure to alloantigens. 3) We found for the first time that miniature swine CD25high+ represents the homologous population to the murine and human Tregs. Miniature swine Tx models, therefore, may provide opportunities for pre-clinical evaluation of innovative Tregs-based tolerance strategy.

Changes of inlet temperature, mass flow rate and composition of flue gas, or of water/steam pressure and temperature in heat recovery steam generator (HRSG), all will modify the amount of waste heat recovered from flue gas; this brings forward a desire for the optimization of the design of HRSG. For single pressure HRSGs with given structures and specified values of inlet temperature, mass flow rate and composition of flue gas, the steam mass flow rate and gas outlet temperature of the HRSG are analyzed as functions of several parameters. This analysis is based on the laws of thermodynamics, incorporated into the energy balance equations for the heat exchangers. Those parameters are superheated steam pressure and temperature, feedwater temperature and pinch point temperature difference. It was shown that the gas outlet temperature could be lowered by selecting appropriate water/steam parameters and pinch point temperature difference. While operating with the suggested parameters, the HRSG can generate more high-quality steam, a fact of great significance for waste heat recovery from wider ranges of sources for better energy conservation.

It has been reported that polyphenols in red wine have potentially protective effects such as vasodilation, lowering blood pressure, reduction of endothelin synthesis, antioxidation, anticancer effects, and inhibition of kinases, whereas the precise mechanism underlying the polyphenol effects remains obscure. In this study, patch-clamp test was employed in order to examine the effect of three major polyphenols, quercetin, resveratrol, and catechin, extracted from red wine on sodium channel currents in mouse dorsal root ganglia cells. The three polyphenols more or less suppressed the sodium channel activity in a concentration-dependent manner. This suggests the sedative impact of polyphenols on the neuronal excitation.

Objective: To investigate the correlation among CD4+CD25+ Treg cell frequency, CTLA-4 expression level in the peripheral blood mononuclear cells (PBMC), and disease progression of HIV/AIDS patents. Methods: Fifty HIV/AIDS-positive samples were confirmed by both Zhejiang Provincial and Hangzhou Center for Disease Control and Prevention. Ten samples of healthy volunteers were randomly selected as controls. Immune cells were counted using a flow cytometer (FACS), and the expression level of CTLA-4 mRNA analyzed using RT-PCR. Results: CD4+CD25+ Treg cells in PBMC of HIV/AIDS patients were markedly higher than those of healthy volunteers£ ̈P = 0.04j, and CTLA-4 mRNA was highly expressed in the CD4+CD25+ Treg subpopulation (P = 0.002), compared to healthy adults as well as AIDS patients treated with HAART. Conclusion: CTLA-4 expressed on CD4+CD25+ Treg cells can be a specific marker of the progression of HIV/AIDS, and the inhibitory receptor may play an important role in the regulation and pathogenesis of HIV/AIDS.

The SCID mouse (severe combined immunodeficiency mouse) has been used as a small animal model in the analysis of human pathophysiology and preclinical experiment for many years. As the most difficult challenge faced in the research of AIDS, chronic hepatitis B and chronic hepatitis C is the lack of appropriate small animal model, researchers have always attempted to develop a series of mouse models based on the improvements of the SCID mouse. This review focuses on the developments and applications of such SCID mouse models in three types of the above chronic infectious diseases.

With the growing demand of wireless applications, radio spectrum has become a scare resource. Cognitive Radio (CR) technology has been considered as an important solution to optimize the utilization of natural frequency spectrum. Numerous researches are performed on deploying CR in cellular networks. In this paper, we introduced new challenges on integration of CR technology and Wireless Sensor Networks (WSN), and some potential solutions are proposed.

Liquefactions have been carried out on plantation fir scrap, with allylimidazolium ionic liquids as liquefaction agent. The primary component of plantation fir was analyzed, fir scrap properties were tested in contrast to peeled fir. Single-factor experiments were employed to discuss the influential factors liquefying plantation fir scrap by ionic liquids. The results showed that the appropriate conditions of liquefaction were 80℃, 30min, and the ratio of wood to liquor was 7:1, in these conditions, the liquefaction is nearly complete.

A MDI-based waterborne polyurethane emulsion(PU) was synthesized by the reaction of polyester glycol(PBA), di-methylol propionic acid(DMPA) with 4,4`-diphenylmethane diisocyanate (MDI) instead of toluene di-isocyanatotoluene(TDI) because of its low toxicity, low saturated vapor pressure. The factors influencing the properties of waterborne polyurethane emulsion were discussed. It was observed that the appearance and properties of the PU emulsion were nearly related with the ratio of NCO/OH(R) and the amount of DMPA.

The ability of G-quadruplex ligands to induce formation of four-stranded DNA and stabilize four-stranded DNA make them able to inhibit telomerase. This paper investigated the interaction of four perfluoroalkyl phthalocyanine metal derivatives with telomeric DNA sequence 5’-d [TTAGGG)4TT-3’ by using circular dichrosim (CD), ultraviolet-visible and fluorescence spectroscopy, and molecular simulation method. Results show that perfluoroalkyl Zinic phthalocyanine can strongly induce the G-DNA in the buffer without extra K+/Na+ added with a molar ratio of 1:1 interaction possibly by intercalation into G-quartets, and only increases the amount of G-DNA in the presence of K+/Na+, with a compound/DNA 2:1 interaction possibly by external stacking model.

Sorption potential of hemp powders as sorbents converted from wasted hemp fibers for Zn2+ ions from diluted aqueous solution was explored. Spectrophotometric method was selected to determine the concentration of Zn2+ ions in the solutions. The influence of different factors on the sorption, such as pH, amount of hemp powder applied as well as initial concentration, were studied, respectively. The obtained results show that the sorption capacity for Zn2+ was the maximum when the pH was 5.85. Increasing the initial concentration of the solutions resulted in increased sorption capacity. Depressed uptake capacity was obtained while amount of hemp powders was increased.

Shape controlling is a popular topic in curves and surfaces design with free form. In this paper, a new curve, to be called Biquadratic TC-Bézier curves with shape parameter , is constructed in the space . We show that such curves share the same properties as the traditional Bézier curves in polynomial spaces. The shape of new curves, representing circle and ellipse accurately, can be adjusted by changing the value of the parameter . Then we give the G1 continuity conditions of Biquadratic TC-Bézier curves with shape parameter and its application in surfaces modeling.

Hepatocyte growth factor (HGF) is a multifunctional cytokine with mitogenic, motogenic, morphogenic, and tumor-suppressing activities. Despite the broad spectrum of its biological activities, HGF is most likely the physiological hepatotrophic factor that triggers or modulates liver regeneration. Regulatory mechanisms for HGF production are crucial for understanding the control of liver regeneration. We previously reported that HGF production by human skin fibroblasts is stimulated by a protein kinase C (PKC)-mediated pathway. We determined here whether gene expression and production of HGF in human skin fibroblasts can be induced via activation of a cAMP-mediated pathway. HGF secretion by the cells was markedly stimulated by the cAMP-elevating agents, forskolin, cholera toxin, prostaglandin E2(PGE2), and 3-isobutyl-1-methylxanthine, as well as by the membrane-permeable cAMP analogues, 8-bromo-cAMP and dibutyryl cAMP. The dose-response curves of induction of HGF secretion by cholera toxin and forskolin were nearly parallel with those of the intracellular cAMP levels. HGF mRNA levels did not significantly increase at 5 and 10 h, but increased considerably 15 h or more after the addition of cholera toxin. Forskolin, 8-bromo-cAMP, and PGE2also caused appreciable up-regulation of HGF gene expression with a similar time course. Although human skin fibroblasts of various origins secreted variable amounts of HGF, the cAMP-elevating agents and the cAMP analogues caused a very marked increase in HGF production in all of them. The agents also enhanced highly active HGF secretion by MRC-5 human embryonic lung fibroblasts. Dexamethasone and transforming growth factor-β1, which inhibit PKC-mediated HGF secretion, down-regulated HGF mRNA expression and HGF production in the cells treated with the cAMP-elevating agents and the cAMP analogues. These results indicate that HGF expression in human skin fibroblasts is stimulated by activation of a cAMP-mediated pathway.

During an outbreak of hemorrhagic fever with renal syndrome in the Anhui Province of China, a door-to-door survey was conducted of all of the 10,024 residents of eight village communities. The incidence rates were higher in males than in females and higher in adults than in children. Of all the residents surveyed, however, those who had slept on the ground or had been engaged in heavy farm work were at a significantly higher risk of illness than were those who slept on wooden beds or did light work. Among men who did heavy farm work and who gave a history of sleeping in straw huts on the drained swamp, the attack rate was 2.33 times higher than it was for those sleeping exclusively in their permanent homes. Among both sexes, threshers had a significantly higher attack rate than did nonthreshers. Suspicions that trombiculid mites or gamasoid mites act as vehicles of transmission cannot be accepted as an explanation for the association of the risk of illness with the type of work done and with sleeping arrangements. Circumstantial evidence supports our hypotheses of airborne transmission and transmission by inoculation of infectious materials into skin lesions.