Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins.

The ongoing outbreak of viral pneumonia in China and across the world is associated with a new coronavirus, SARS-CoV-21. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection2. Although bats are probable reservoir hosts for SARS-CoV-2, the identity of any intermediate host that may have facilitated transfer to humans is unknown. Here we report the identification of SARS-CoV-2-related coronaviruses in Malayan pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin-associated coronaviruses that belong to two sub-lineages of SARS-CoV-2-related coronaviruses, including one that exhibits strong similarity in the receptor-binding domain to SARS-CoV-2. The discovery of multiple lineages of pangolin coronavirus and their similarity to SARS-CoV-2 suggests that pangolins should be considered as possible hosts in the emergence of new coronaviruses and should be removed from wet markets to prevent zoonotic transmission.

Discovery and synthesis of novel glyrrhizin-analogs containing furanoylpiperazine and the activity against myocardial injury in sepsis.

The signaling pathway mediated by high mobility group protein B1 (HMGB1) plays a key role in myocardial injury during sepsis. Glyrrhizin (GL) is a natural product that inhibits HMGB1 biological activities through forming GL-HMGB1 complex; the research shows its aglycone (GA) is the main pharmacophore binding to HMGB1, while the glycosyl mainly altering its pharmacokinetic properties and enhances the stability of the complex. GL is often metabolized to GA in the gastrointestinal tract, which has a lower efficacy in the treatment of HMGB1-mediated diseases. To obtain the GL analogs with higher activity and better pharmacokinetic properties, 24 GL analogs were synthesized by simplification the glycosyl of GL. Among all the compounds, compound 11 with furanoylpiperazine was screened. The pharmacokinetics experiments showed that compound 11 is converted to 11a in vivo, and 11 serves as its prodrug. Compound 11a displayed a lower cytotoxicity to RAW264.7 cells and three types of cardiomyocyte lines, with IC50 > 800 µM. In the anti-inflammatory assay, 11a not only strongly inhibited NO production (IC50 5.73 µM), but also down-regulated the levels of HMGB1, IL-1ß and TNF-α in a dose-dependent manner; in the anti-oxidative stress assay, compound 11a reduced the level of ROS and increased the MMP in H9c2 cells. More importantly, in the myocardial injury model of septic mice, compound 11a not only alleviated the symptom of myocardial injury by reducing inflammatory infiltration and oxidative stress, but also improved the myocardial blood supply by shrinking the inner diameter of the left ventricle and increasing the ejection fraction (EF) more dramatically (155.8 %); meanwhile, compound 11a adjusted myocardial enzymes in serum of septic mice. In addition, in molecular docking experiments, compound 11a showed stronger HMGB1 binding ability than GL. In summary, compound 11 is a prodrug, which can be converted to 11a in vivo. And compound 11a has a good activity against septic myocardial injury, as well as improving the myocardial blood supply function. This suggests compound 11 is a potential drug candidate for the treatment of septic myocardial injury and deserves further investigate.

Amelioration impact of gut-brain communication on obesity control by regulating gut microbiota composition through the ingestion of animal-plant-derived peptides and dietary fiber: can food reward effect as a hidden regulator?

Various roles of intestinal flora in the gut-brain axis response pathway have received enormous attention because of their unique position in intestinal flora-derived metabolites regulating hormones, inducing appetite, and modulating energy metabolism. Reward pathways in the brain play a crucial role in gut-brain communications, but the mechanisms have not been methodically understood. This review outlined the mechanisms by which leptin, ghrelin, and insulin are influenced by intestinal flora-derived metabolites to regulate appetite and body weight, focused on the significance of the paraventricular nucleus and ventromedial prefrontal cortex in food reward. The vagus nerve and mitochondria are essential pathways of the intestinal flora involved in the modulation of neurotransmitters, neural signaling, and neurotransmission in gut-brain communications. The dynamic response to nutrient intake and changes in the characteristics of feeding activity requires the participation of the vagus nerve to transmit messages to be completed. SCFAs, Bas, BCAAs, and induced hormones mediate the sensory information and reward signaling of the host in the complex regulatory mechanism of food selection, and the composition of the intestinal flora significantly impacts this process. Food reward in the process of obesity based on gut-brain communications expands new ideas for the prevention and treatment of obesity.

Design and synthesis of salidroside analogs and their bioactivity against septic myocardial injury.

Cardiac tissue suffers much from sepsis, and the incidence of myocardial injury is high in septic patients. The treatment of sepsis myocardial injury (SMI) has been the focus of clinical medicine. Salidroside shows myocardial cell protection, anti-oxidation and anti- inflammation effects, and it is thought as one of the potential compounds to treat sepsis myocardial injury. However, its anti-inflammatory activity is lower and its pharmacokinetic properties are not ideal, which is far from clinical application. Here, a series of salidroside analogs were synthesized, and their bioactivities were evaluated from several aspects, including their anti-oxidant and anti-inflammatory activities in vitro and anti-sepsis myocardial injury activities in vivo. Of all the compounds which synthesized, compounds 2 and 3 exhibited stronger anti-inflammatory activities than the others; after treating LPS-stimulated RAW264.7 or H9c2 cells with each of them, the levels of IL-1ß, IL-6 and TNF-α were down-regulated in a dose-dependent manner. In the anti-oxidative stress injury test, compounds 2 and 3 not only markedly increased the survival rate of cells, and but also improved the cellular oxidative stress-related indicators MDA, SOD and cell damage marker LDH in a dose-dependent manner. In the LPS-induced septic rat myocardial injury models (in vivo), the two compounds also showed good bioactivities. They also reduced the expression of IL-1ß, IL-6 and TNF-α, and blocked cell damage by suppressing overhauled oxidation in septic rats. In addition, the myocardial injury was significantly improved and the inflammatory infiltration was reduced after treatment with the two compounds. In conclusion, the salidroside analogs (2 and 3) showed promising therapeutical effect on septic myocardial injury in LPS-model rats, and they could be good candidates for clinical trials against inflammation and septic myocardial injury.

Complete genome sequence of a novel bovine hepacivirus from Yunnan, China.

We detected a novel bovine hepacivirus N (HNV) subtype, IME_BovHep_01, in the serum of cattle in Tengchong, Yunnan, China, by high-throughput sequencing. The complete genome of IME_BovHep_01, was sequenced using an Illumina MiSeq sequencer and found to be 8850 nt in length, encoding one hypothetical protein. BLASTn analysis showed that the genome sequence shared similarity with the bovine hepacivirus isolate BovHepV_209/Ger/2014, with 88% query coverage and 70.8% identity. However, the highest similarity was to bovine hepacivirus N strain BRBovHep_RS963, for which only a partial genome sequence is available, with 68% query coverage and 81.5% identity. Sequence comparisons and phylogenetic analysis suggested that IME_BovHep_01 is a novel HNV subtype. Importantly, IME_BovHep_01 is the first member of this new genotype for which the complete genome sequence was determined.

Isolation and Characterization of a Novel Bacteriophage Infecting Carbapenem-Resistant Klebsiella pneumoniae.

A novel virulent phage, vB_KpnP_IME337, isolated from a hospital sewage in Beijing, China, that infects carbapenem-resistant Klebsiella pneumoniae KN2 capsular type was identified and characterized. Next-generation sequencing and genome analysis revealed that vB_KpnP_IME337 had a linear double-stranded genome with a length of 44,266 base pairs and G+C content of 53.7%. Fifty-two putative open reading frames were identified, and no transfer RNA-encoding genes were detected. BLASTn analysis revealed that phage vB_KpnP_IME337 had the highest sequence similarity with Klebsiella phage phiBO1E, with genome coverage of 79%. Based on morphology, phage vB_KpnP_IME337 was determined to belong to the family Podoviridae of the order Caudovirales. It was shown that phage vB_KpnP_IME337 had an infection duration of ~ 90 min and 10 min latent period, and a highly specific to host strain. In conclusion, phage vB_KpnP_IME337 may be a promising alternative candidate to antibiotic treatment for controlling diseases caused by drug-resistant K. pneumoniae.

Relevance research between the expression of p16INK4a , Notch1, and hTERC genes: The development of HPV16-positive cervical cancer.

BACKGROUND: GLOBOCAN 2018 latest data show cervical cancer ranks fourth in morbidity and mortality among women. Many genes in cervical lesions differ in sensitivity and specificity. However, the diagnostic molecules for early cervical cancer are not very clear. This paper screens biomarkers for early molecular diagnosis of Mongolian patients with cervical cancer. METHODS: Immunohistochemical SP method was used to detect the expression of p16INK4a and Notch1 protein in paraffin sections of 226 Mongolian patients with HPV16-positive cervical lesions after pathological examination, and 100 of them were randomly selected by fluorescence in situ hybridization to detect hTERC gene. The HPV16-binding human cervical cancer SiHa cell line was used to silence the expression of HPV16 E6/E7 gene by RNA interference, and the expression of p16INK4a , Notch1, and hTERC genes and protein expression levels were detected by RT-PCR and Western blot. RESULTS: The positive expression rates of p16INK4a , Notch1, and hTERC genes in HPV16-positive cervical cancer, CIN-III, CIN-II, CIN-I, uterine leiomyoma, and chronic cervicitis were significantly different (P < .05); the positive expression rates of the three genes were also significantly different in the same type of cervical lesions (P < .05); RNA interference can effectively inhibit HPV16 E6/E7, p16INK4a and Notch1 gene expression, but has no effect on hTERC gene expression. CONCLUSION: The p16INK4a gene can be used as a biomarker for early screening of cervical cancer, and the hTERC gene can be used to confirm the clinical diagnosis of cervical cancer.

Advanced glycation end products (AGEs) impair the intestinal epithelial barrier via STAT3 activation mediated by macrophages.

Advanced glycation end products (AGEs) are a spectrum of complex compounds widely found in processed foods and frequently consumed by humans. AGEs are implicated in impairing the intestinal barrier, but the underlying mechanisms remain unclear. This study investigated the effects of three types of AGEs on gene expression of tight junctions (TJs) in colorectal epithelial HT-29 cells, and observed minimal alterations in TJs expression. Given the important role of subepithelial macrophages in regulating the intestinal barrier, we explored whether AGEs affect the intestinal barrier via the involvement of macrophages. Notably, a significant downregulation of TJs expression was observed when supernatants from AGEs-treated RAW264.7 macrophage cells were transferred to HT-29 cells. Further investigations indicated that AGEs increased IL-6 levels in RAW264.7 cells, subsequently triggering STAT3 activation and suppressing TJs expression in HT-29 cells. The role of STAT3 activation was confirmed by observing enhanced TJs expression in HT-29 cells following pretreatment with an inhibitor of STAT3 activation prior to the transfer of the conditioned medium. These findings demonstrated that AGEs impaired the intestinal barrier via macrophage-mediated STAT3 activation, shedding light on the mechanisms underlying AGEs-induced intestinal barrier injury and related food safety risks.

Perfluorooctanoic acid (PFOA) and its alternative perfluorobutanoic acid (PFBA) alter hepatic bile acid profiles via different pathways.

The disruption of per- and polyfluoroalkyl substances (PFASs) on bile acid (BA) homeostasis has raised public concerns, making the evaluation of their effects and underlying mechanisms a high priority. Although the use of perfluorooctanoic acid (PFOA) has been restricted, it remains a widespread legacy PFAS in the environment. Concurrently, the use of its prevalent short-chain alternative, perfluorobutanoic acid (PFBA), is increasing, yet the toxicity assessment of PFBA remains inadequate. In this study, C57BL/6N mice were exposed to PFOA and PFBA (0.4 or 10 mg/kg body weight) by gavage for 28 days. The results showed that both PFOA and PFBA significantly increased hepatic weight, although PFBA exhibited lower bioaccumulation than PFOA in the liver. Targeted metabolomics revealed that PFOA significantly decreased total BA levels and altered their composition. Conversely, PFBA, without significantly altering total BA levels, notably changed their composition, such as increasing the proportion of cholic acid. Further investigations using in vivo and in vitro assays suggested that PFOA inhibited the expression of Cyp7A1, a key BA synthetase, potentially via PPARα activation, thereby reducing BA levels. In contrast, PFBA enhanced Cyp7A1 expression, associated with the inhibition of intestinal Farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) pathway. This study evaluated the differences in the BA-interfering effects of PFOA and PFBA and shed light on the potential mechanisms, which will provide new insights into the health risks of legacy PFASs and their alternatives.

Liposome-quantum dot complexes enable multiplexed detection of attomolar DNAs without target amplification.

Sensitive detection of DNA usually relies on target amplification approaches such as polymerase chain reaction and rolling circle amplification. Here we describe a new approach for sensitive detection of low-abundance DNA using liposome-quantum dot (QD) complexes and single-particle detection techniques. This assay allows for detection of single-stranded DNA at attomolar concentrations without the involvement of target amplification. Importantly, this strategy can be employed for simultaneous detection of multiple DNA targets.

A preliminary review of Isonychia Eaton, 1871 from Chinese mainland with a re-description of I.kiangsinensis Hsu, 1936 (Insecta, Ephemeroptera, Isonychiidae).

Previously, seven species of the genus Isonychia Eaton, 1871 were reported in China, but they have never been systematically reviewed. After examining our collections from the Chinese mainland, six species and one additional subspecies have been recognized, compared, and photographed. Among them, I.kiangsinensis is redescribed in all stages and a neotype is designated. Its males have triangular penes and nymphs have three dark pigments on each gill. A synonym of I.guixiensisWu et al., 1992 (I.sinensisWu et al., 1992) is confirmed. The males of this species have nearly cylindrical penes and clear abdominal markings. Finally, two species and one subspecies are recorded for the first time in China: I.ussuricasibiricaTiunova et al., 2004, I.ussuricaussurica Bajkova, 1970 and I.vshivkovaevshivkovaeTiunova et al., 2004. Together with the I.ignota (Walker, 1853), I.sexpetalaTiunova et al., 2004, I.formosana (Ulmer, 1912) and possible I.japonica (Ulmer, 1920), they show the rich diversity of the genus Isonychia in China.

Synthesis of glycyrrhizin analogues as HMGB1 inhibitors and their activity against sepsis in acute kidney injury.

Glycyrrhizin (GL) is one of the antagonists of highly conserved nuclear protein (HMGB1). The researches have shown that the glycosyl of GL is an important pharmacophore for GL binding to HMGB1, and it is the determinant factor for mechanism of action. To get the HMGB1 inhibitors with higher activity and good pharmacokinetic properties, two classes of GL analogues containing C-N glycoside bond were synthesized, and their anti-inflammatory, anti-oxidative stress and anti-septic kidney injury were evaluated. The results are as follows. First, in the anti-inflammatory assay, all the compounds inhibited NO release in some degree; among them, compound 6 displayed the strongest NO inhibitory effect with IC50 value of 15.9 µM, and compound 15 with IC50 of 20.2 µM. The two compounds not only decreased IL-1ß and TNF-α levels in RAW264.7 cells and HK-2 cells, but also downregulated the levels of NLRP3, P-NF-κB p65 and HMGB1 in activated HK-2 cells in a dose-dependent manner. Second, in the renal protection assay with H2O2-stimulated HK-2 cell line, they reduced MDA level and increased SOD in HK-2 cells; additionally, they also inhibited the HK-2 cell apoptosis and downregulated the Caspase-1 p20 level. Third, in the in vivo activity tests of the septic mouse, they also showed good activities just like in vitro, decreasing the IL-1ß, TNF-α, MDA, blood creatinine (Scr) and urea nitrogen (BUN) in serum, and increasing SOD levels in a dose-dependent manner. The immunoblotting results showed the two compounds downregulated the levels of HMGB1, P-NF-κB p65, NLRP3 and Caspase-1 p20 protein. All in all, the two compounds improved the renal injury of septic mice, and alleviated the tube wall structure damage and renal tubular dilation in kidney, which further proved by H&E staining. This suggests the two compounds have septic acute kidney injury activity, and they will be potential therapeutic drugs for septic acute kidney injury.

Exploring novel ANGICon-EIPs through ameliorated peptidomics techniques: Can deep learning strategies as a core breakthrough in peptide structure and function prediction?

Dairy-derived angiotensin-I-converting enzyme inhibitory peptides (ANGICon-EIPs) have been regarded as a relatively safe supplementary diet-therapy strategy for individuals with hypertension, and short-chain peptides may have more relevant antihypertensive benefits due to their direct intestinal absorption. Our previous explorations have confirmed that endogenous goat milk short-chain peptides are also an essential source of ANGICon-EIPs. Nonetheless, there are limited explorations on endogenous ANGICon-EIPs owing to the limitations of the extraction and enrichment of endogenous peptides, currently. This review outlined ameliorated pre-treatment strategies, data acquisition methods, and tools for the prediction of peptide structure and function, aiming to provide creative ideas for discovering novel ANGICon-EIPs. Currently, deep learning-based peptide structure and function prediction algorithms have achieved significant advancements. The convolutional neural network (CNN) and peptide sequence-based multi-label deep learning approach for determining the multi-functionalities of bioactive peptides (MLBP) can predict multiple peptide functions with absolute true value and accuracy of 0.699 and 0.708, respectively. Utilizing peptide sequence input, torsion angles, and inter-residue distance to train neural networks, APPTEST predicted the average backbone root mean square deviation (RMSD) value of peptide (5-40 aa) structures as low as 1.96 Å. Overall, with the exploration of more neural network architectures, deep learning could be considered a critical research tool to reduce the cost and improve the efficiency of identifying novel endogenous ANGICon-EIPs.

Iodine release and recovery, influence of polyiodide anions on electrical conductivity and nonlinear optical activity in an interdigitated and interpenetrated bipillared-bilayer metal-organic framework.

{[Cu6(pybz)8(OH)2]·I5(­)·I7(­)}n (1), obtained hydrothermally by using iodine molecules as a versatile precursor template, consists of a cationic framework with two types of zigzag channels, which segregate I5(­) and I7(­) anions. The framework exhibits the first observed bipillared-bilayer structure featuring both interdigitation and interpenetration. 1 displays high framework stability in both acidic (HCl) and alkaline (NaOH) solutions. 1 slowly releases iodine in dry methanol to give [Cu6(pybz)8(OH)2](I­)2·3.5CH3OH (1') and partially recovers iodine from cyclohexane to form [Cu6(pybz)8(OH)2](I­)2·xI2 (1″). Differences of up to 100 times in electrical conductivity and of 4 times in nonlinear optical activity (NLO) have been measured between 1 and 1'. This compound is one of few displaying multifunctionality, electrical conductivity, NLO, and crystal­crystal stability upon release and recovery of iodine. It is also unique in the iodine release from polyiodide anions in a metal­organic framework.

Design and synthesis of bile acid derivatives and their activity against colon cancer.

Bile acids (BAs) containing both hydrophilic hydroxyl and carboxyl groups and hydrophobic methyl and steroid nuclei can promote the absorption of fat and other substances in the intestine, and they are synthesized by cholesterol in the liver and then returned to the liver through enteric liver circulation. Because there are many BA receptors on the cell membrane of colon tissues, BAs can improve the specific delivery and transport of medicines to colon tissues. Moreover, BAs have a certain anticancer and inflammation activity by themselves. Based on this theory, a series of BA derivatives against colon cancer including cholic acid (CA), chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA) and lithocholic acid (LCA) were designed and synthesized, and their antitumor activity was evaluated. For in vitro anti-tumor tests, all the compounds displayed cell proliferative inhibition to nine human malignant tumor cell lines to some degree, and in particular they showed stronger inhibition to the colon cancer cells than the other cell lines. Among them, four compounds (4, 5, 6, and 7) showed stronger activity than the other compounds as well as the positive control 5-FU against HCT116 cells, and their IC50 was between 21.32 µmol L-1 and 28.90 µmol L-1; cell clone formation and migration tests showed that they not only effectively inhibited the formation of HCT116 cell colonies, but also inhibited the HCT116 cell migration and invasion; moreover, they induced apoptosis, arrested the mitotic process at the G2/M phase of the cell cycle, reduced the mitochondrial membrane potential, increased the intracellular ROS levels, and reduced the expression of Bcl-2 and p-STAT3 in HCT 116 cells. In addition, they also displayed intermediate anti-inflammatory activity by inhibiting inflammatory mediators NO and downregulating TNF-α expression, which also is one of the causes of colon cancer. This suggests that they deserve to be further investigated as candidates for colon cancer treatment drugs.

Oriented synthesis of one-dimensional polypyrrole molecule chains in a metal-organic framework.

We report for the first time the preparation of single polypyrrole (PPy) molecule chains using a "metal-organic framework" with 1 nm channels as a template. The obtained one-dimensional (1-D) PPy has highly structure order and excellent conductivity, which has improved by as much as five orders of magnitude in comparison with that of 2-D PPy.

Rigid pillars and double walls in a porous metal-organic framework: single-crystal to single-crystal, controlled uptake and release of iodine and electrical conductivity.

A highly stable pillared and double-walled zinc(II) metal-organic framework with regular nanochannels displays single-crystal to single-crystal transformation upon desolvation and a large quantity of iodine uptake, controlled release, and electrical conductivity elevation due to synergy between the iodine guests and the host framework.

Virome diversity analysis reveals novel enteroviruses and a human picobirnavirus in stool samples from African green monkeys with diarrhea.

It is important to identify viruses in animals because most infectious diseases in humans are caused by viruses of zoonotic origin. African green monkey is a widely used non-human primate model in biomedical investigations. In this study, total RNAs were extracted from stool samples of 10 African green monkeys with diarrhea. High-throughput sequencing was used to characterize viromes. PCR and Sanger sequencing were used to determine the full genome sequences. Great viral diversity was observed. The dominant viruses were enteroviruses and picobirnaviruses. Six enterovirus genomes and a picobirnavirus RNA-dependent RNA polymerase sequence were characterized. Five enteroviruses belonged to two putative new genotypes of species Enterovirus J. One enterovirus belonged to EV-A92. The picobirnavirus RNA-dependent RNA polymerase sequence had the highest nucleotide similarity (93.48%) with human picobirnavirus isolate GPBV6C2. The present study helped to identify the potential zoonotic viruses in African green monkeys. Further investigations are required to elucidate their pathogenic roles in animals and humans.

Tetra-aqua-bis[3-(4-pyrid-yl)benzoato-κN]nickel(II).

The Ni(II) atom in the title compound, [Ni(C(12)H(8)NO(2))(2)(H(2)O)(4)], exists in an all-trans octa-hedral coordination environment. The 3-(4-pyrid-yl)benzoate ligand binds to Ni atom through the pyridyl N atom; the pyridine and benzene rings are oriented at a dihedral angle of 26.27 (10)°. Adjacent complexes are linked by O-H⋯O hydrogen bonds, forming a three-dimensional network. The metal atom lies on a special position of 2 site symmetry in the crystal structure.

[Immune and inflammation confusion in severe sepsis and effects of bi-immunomodulation therapy: a prospective, randomized, controlled clinical trial].

OBJECTIVE: To investigate the immune and inflammation confusion state in severe sepsis and the effects of two way immunomodulation therapy with continuous blood purification (CBP), thymosin alpha1, and combined therapy of CBP and thymosin alpha(1). METHODS: 91 Patients with severe sepsis aged > 18, with Marshall score>5. were randomly divided into 4 groups: CBP Group (n = 22) undergoing continuous renal replacement therapy (CRRT) or molecular adsorbents recirculating system (MARS) therapy once a day for 3 days in addition to classical Surviving Sepsis Campaign (SSC) therapy, Thymosin alpha(1) Group (n = 23) undergoing subcutaneous injection of thymosin alpha(1) 1.6 mg once a day for 7 days in addition to SSC therapy, Combined Therapy Group (n = 22) undergoing CBP combined with thymosin alpha(1) treatment in addition to SSC therapy, and SSC Group (treatment control group, n = 24) undergoing SSC therapy only. Peripheral blood samples were collected before treatment, and 3 and 7 days after the beginning of treatment (days 4 and 8) to detect the serum interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha. The levels of CD(14)(+) monocyte human leucocyte antigen (HLA)-DR and T lymphocytes were monitored. The mechanical ventilation time, ICU stay length, and mortality within 28 d and mortality within 90 d were observed. Ten healthy persons were used as healthy control group. RESULTS: Thirty-four of the 91 patients died within 28 d with a mortality of 77.4% (Death Group) and other 57 patients were put in Survival Group. The levels of serum IL-6, IL-10, and TNFalpha, and IL-6/IL-10 at different time points of both Death and Survival Groups were all significantly higher, and the HLA-DR level, and CD(3)(+), CD(4)(+), and CD(8)(+) T lymphocyte numbers at different time points of both Death and Survival Groups were all significantly lower than those of the healthy controls (P < 0.05 or < 0.01). The levels of serum IL-6, IL-6/IL-10, TNFalpha, HLA-DR, and CD(3)(+), CD(4)(+), and CD(8)(+) T lymphocyte at different time points of Death Group were all significantly higher than those of Survival Group (P < 0.05 or < 0.01). The CD(3)(+) T lymphocyte number on day 8 of Thymosin Group was significantly higher than that of SSC Group (all P < 0.05). The serum IL-6 and TNFalpha and IL-6/IL-10 were decreased, and HLA-DR, and CD(3)(+), CD(4)(+), and CD(8)(+) were increased significantly on day 8 in CBP and Combined Therapy Groups. The level of TNFalpha decreased, and the numbers of CD(3)(+) and CD(4)(+) T lymphocytes increased significantly on day 4 in Combined Therapy Group (P < 0.05 or P < 0.01). Compared with Thymosin Group, almost all the indexes of CBP and Combined Therapy Groups were improved, only the CD(3)(+) T lymphocyte level on day 4 increased and the IL-6/IL-10 ratio on day 8 was decreased significantly in Combined Therapy Group (both P < 0.05). Compared with those of SSC Group, the mechanical ventilation time, length of ICU stay within 28 days, and 28 days mortality and 90 days mortality of the 3 treatment groups were all decreased, and there were statistical differences in the length of ICU stay of CBP Group and in the mechanical ventilation time and length of ICU stay within 28 days of Combined Therapy Group (both P < 0.05). CONCLUSION: Systemic inflammatory response and immunodepression exist simultaneously in severe sepsis. Thymosin alpha(1) increases the cellular immunity, and CBP bi-modulates the immune turbulence, reduces the inflammatory mediators, and ameliorates the immune homeostasis. These 2 therapies also improve the clinical prognosis and the combination of both would be more effective.