Pathologic complete response after photodynamic therapy combined with dose-reduction chemoradiotherapy in elderly patient with severe obstruction esophageal carcinoma: A case report.

Esophageal Carcinoma (EC) is one of the most aggressive gastrointestinal cancers. Advanced esophageal carcinoma is associated mainly with dysphagia which reduces the quality of life and leads to frail in patients even difficult to tolerate systemic treatments such as surgery and chemoradiotherapy. Moreover, chemoradiotherapy(CRT)cannot relieve dysphagia in a short time especially for the elderly patient with comorbidities. Here, we report a 76-year-old female patient diagnosed with severe obstructive esophageal squamous cell carcinoma (ESCC) that endoscope could not pass through. She was also complicated with bilateral interstitial pneumonia and moderate pulmonary ventilation dysfunction. The patient was unable to undergo surgery and radical CRT. After multidisciplinary team (MDT) discussion, we gave the patient photodynamic therapy (PDT) treatment firstly. The obstruction was significantly improved within 1 week and normal diet was resumed after 2 weeks. Four weeks later, considering bilateral interstitial pneumonia, concurrent dose-reduction chemoradiotherapy was given for esophageal lesions and abdominal metastatic lymph nodes. There was no recurrence and progression in the esophagus and abdominal lymph nodes until now and the biopsy of the primary esophageal lesion showed pathologic complete response. Now, the patient is still under regular follow-up.

[Comparison of effectiveness of lower extremity axial distractor and traction table assisted closed reduction and intramedullary nail fixation in femoral subtrochanteric fracture].

Objective: To compare the effectiveness of lower extremity axial distractor (LEAD) and traction table assisted closed reduction and intramedullary nail fixation in treatment of femoral subtrochanteric fracture. Methods: The clinical data of 117 patients with subtrochanteric fracture of femur treated by closed reduction and intramedullary nail fixation between May 2012 and May 2022 who met the selection criteria were retrospectively analyzed. According to the auxiliary reduction tools used during operation, the patients were divided into LEAD group (62 cases with LEAD reduction) and traction table group (55 cases with traction table reduction). There was no significant difference in baseline data, such as gender, age, injured side, cause of injury, fracture Seinsheimer classification, time from injury to operation, and preoperative visual analogue scale (VAS) score, between the two groups ( P>0.05). Total incision length, operation time, intraoperative blood loss, fluoroscopy frequency, closed reduction rate, fracture reduction quality, fracture healing time, weight-bearing activity time, and incidence of complications, as well as hip flexion and extension range of motion (ROM), Harris score, and VAS score at 1 month and 6 months after operation and last follow-up were recorded and compared between the two groups. Results: There were 14 cases in the LEAD group from closed reduction to limited open reduction, and 43 cases in the traction table group. The incisions in the LEAD group healed by first intention, and no complication such as nerve and vascular injury occurred during operation. In the traction table group, 3 cases had perineal crush injury, which recovered spontaneously in 1 week. The total incision length, operation time, intraoperative blood loss, fluoroscopy frequency, and closed reduction rate in the LEAD group were significantly better than those in the traction table group ( P<0.05). There was no significant difference in the quality of fracture reduction between the two groups ( P>0.05). Patients in both groups were followed up 12-44 months, with an average of 15.8 months. In the LEAD group, 1 patient had delayed fracture union at 6 months after operation, 1 patient had nonunion at 3 years after operation, and 1 patient had incision sinus pus flow at 10 months after operation. In the traction table group, there was 1 patient with fracture nonunion at 15 months after operation. X-ray films of the other patients in the two groups showed that the internal fixator was fixed firmly without loosening and the fractures healed. There was no significant difference in fracture healing time, weight bearing activity time, incidence of complications, and postoperative hip flexion and extension ROM, Harris score, and VAS score at different time points between the two groups ( P>0.05). Conclusion: For femoral subtrochanteric fracture treated by close reduction and intramedullary nail fixation, compared with traction table, LEAD assisted fracture reduction can significantly shorten the operation time, reduce intraoperative blood loss and fluoroscopy frequency, reduce incision length, effectively improve the success rate of closed reduction, and avoid complications related to traction table reduction. It provides a new method for good reduction of femoral subtrochanteric fracture.

Crystal structures of OrfX1, OrfX2 and the OrfX1-OrfX3 complex from the orfX gene cluster of botulinum neurotoxin E1.

Botulinum neurotoxins (BoNTs) are among the most lethal toxins known to humans, comprising seven established serotypes termed BoNT/A-G encoded in two types of gene clusters (ha and orfX) in BoNT-producing clostridia. The ha cluster encodes four non-toxic neurotoxin-associated proteins (NAPs) that assemble with BoNTs to protect and enhance their oral toxicity. However, the structure and function of the orfX-type NAPs remain largely unknown. Here, we report the crystal structures for OrfX1, OrfX2, and an OrfX1-OrfX3 complex, which are encoded in the orfX cluster of a BoNT/E1-producing Clostridium botulinum strain associated with human foodborne botulism. These structures lay the foundation for future studies on the potential roles of OrfX proteins in oral intoxication and pathogenesis of BoNTs.

Quick mass-production of MAX (Ti2AlC) book with pages separated by stacking faults benefiting removal of "A" layer.

A creative and universal technique, magnetism and vortex current coupling growth (MVC), has been developed for the super-rapid mass-production of the layered MAX (Ti2AlC) phase. The book-like MAX grows from the bottom to the top layer by layer, separated by stacking faults to benefit the removal of the "A" layer from MAX.

Biological characteristics of dengue virus and potential targets for drug design.

Dengue infection is a major cause of morbidity in tropical and subtropical regions, bringing nearly 40% of the world population at risk and causing more than 20,000 deaths per year. But there is neither a vaccine for dengue disease nor antiviral drugs to treat the infection. In recent years, dengue infection has been particularly prevalent in India, Southeast Asia, Brazil, and Guangdong Province, China. In this article, we present a brief summary of the biological characteristics of dengue virus and associated flaviviruses, and outline the progress on studies of vaccines and drugs based on potential targets of the dengue virus.

Controllable conversion of liquid silicon from high-density to low-density towards amorphous silicon nanospheres on a wafer scale.

High-density liquid (HDL) silicon can be converted via annealing in hydrogen into low-density liquid (LDL), surviving due to hydrogen protection. Amorphous silicon (a-Si) spheres on a wafer scale were achieved via an underlying transition from LDL silicon. The amorphous spheres were protected from crystallization due to the presence of hydrogen gas.

The hypothetical protein P47 of Clostridium botulinum E1 strain Beluga has a structural topology similar to bactericidal/permeability-increasing protein.

Botulinum neurotoxins (BoNTs) are causative agents of the life-threatening disease botulism. They are naturally produced by species of the bacteria Clostridium botulinum as stable and non-covalent complexes, in which the BoNT molecule is assembled with several auxiliary non-toxic proteins. Some BoNT serotypes, represented by the well-studied BoNT serotype A (BoNT/A), are produced by Clostridium strains that carry the ha gene cluster, which encodes four neurotoxin-associated proteins (NTNHA, HA17, HA33, and HA70) that play an important role to deliver and protect BoNTs in the gastrointestinal tract during oral intoxication. In contrast, BoNT/E- and BoNT/F-producing strains carry a distinct gene cluster that encodes five proteins (NTNHA, P47, OrfX1, OrfX2, and OrfX3, termed the orfX cluster). The structures and functions of these proteins remain largely unknown. Here, we report the crystal structure of P47 resolved at 2.8 Å resolution. Surprisingly, P47 displays a structural topology that is similar to bactericidal/permeability-increasing (BPI) like proteins, which were previously identified only in eukaryotes. The similarity of a hydrophobic cleft of P47 with the phospholipid-binding groove of BPI suggests that P47 might be involved in lipid association to exert its function. Consistently, P47 associates and induces aggregation of asolectin-containing liposomes in a protein- and lipid-concentration dependent manner. These findings laid the foundation for future structural and functional studies of the potential roles of P47 and OrfX proteins in facilitating oral intoxication of BoNTs.

Towards well-defined MoS2 nanoribbons on a large scale.

High quality molybdenum dioxide plates are engineered as templates for epitaxial growth of well-defined MoS2 nanoribbons (MNRs). The obtained MNRs possess prominent ferromagnetism, suggesting edge zigzag topologies. Our findings have opened an alternative route to large-scale synthesis of well-defined 1D materials.

Allosteric opening of the polypeptide-binding site when an Hsp70 binds ATP.

The 70-kilodalton (kDa) heat-shock proteins (Hsp70s) are ubiquitous molecular chaperones essential for cellular protein folding and proteostasis. Each Hsp70 has two functional domains: a nucleotide-binding domain (NBD), which binds and hydrolyzes ATP, and a substrate-binding domain (SBD), which binds extended polypeptides. NBD and SBD interact little when in the presence of ADP; however, ATP binding allosterically couples the polypeptide- and ATP-binding sites. ATP binding promotes polypeptide release; polypeptide rebinding stimulates ATP hydrolysis. This allosteric coupling is poorly understood. Here we present the crystal structure of an intact ATP-bound Hsp70 from Escherichia coli at 1.96-Å resolution. The ATP-bound NBD adopts a unique conformation, forming extensive interfaces with an SBD that has changed radically, having its α-helical lid displaced and the polypeptide-binding channel of its ß-subdomain restructured. These conformational changes, together with our biochemical assays, provide a structural explanation for allosteric coupling in Hsp70 activity.

Numerical simulations of LNG vapor dispersion in Brayton Fire Training Field tests with ANSYS CFX.

Federal safety regulations require the use of validated consequence models to determine the vapor cloud dispersion exclusion zones for accidental liquefied natural gas (LNG) releases. One tool that is being developed in industry for exclusion zone determination and LNG vapor dispersion modeling is computational fluid dynamics (CFD). This paper uses the ANSYS CFX CFD code to model LNG vapor dispersion in the atmosphere. Discussed are important parameters that are essential inputs to the ANSYS CFX simulations, including the atmospheric conditions, LNG evaporation rate and pool area, turbulence in the source term, ground surface temperature and roughness height, and effects of obstacles. A sensitivity analysis was conducted to illustrate uncertainties in the simulation results arising from the mesh size and source term turbulence intensity. In addition, a set of medium-scale LNG spill tests were performed at the Brayton Fire Training Field to collect data for validating the ANSYS CFX prediction results. A comparison of test data with simulation results demonstrated that CFX was able to describe the dense gas behavior of LNG vapor cloud, and its prediction results of downwind gas concentrations close to ground level were in approximate agreement with the test data.

Small peptides derived from the Lys active fragment of the mung bean trypsin inhibitor are fully active against trypsin.

The Bowman-Birk protease inhibitors have recently attracted attention for their potential as cancer preventive and suppressing agents. They contain two canonical binding loops, both consisting of nine highly conserved residues capable of inhibiting corresponding serine proteases. In this study, we cloned the cDNA of the mung bean trypsin inhibitor, one of the most studied Bowman-Birk protease inhibitors. A modified peptide, Lys33GP, with 33 residues derived from the long chain of the Lys active fragment of mung bean trypsin inhibitor, was successfully expressed in Escherichia coli as a glutathione-S-transferase fusion protein. The recombinant product was obtained with a high yield, and exhibited potent inhibitory activity. Meanwhile, a shorter peptide composed of only 16 residues (the Lys16 peptide), corresponding to the active core of the fragment, was synthesized. Both the recombinant and the synthesized peptides had the same inhibitory activity toward trypsin at a molar ratio of 1 : 1, implying that the Lys16 peptide with two disulfide bonds is possibly the essential structural unit for inhibitory activity. Using site-directed mutagenesis, the P(1) position Lys was replaced by Phe, and the resulting mutant, Lys33K/F, was determined to have potent chymotrypsin inhibitory activity. Both Lys33GP and the Lys33K/F mutant may be potential pharmaceutical agents for the prevention of oncogenesis.

Structural features and molecular evolution of Bowman-Birk protease inhibitors and their potential application.

The Bowman-Birk inhibitors (BBIs) are well-studied serine protease inhibitors that are abundant in dicotyledonous and monocotyledonous plants. BBIs from dicots usually have a molecular weight of 8k and are double-headed with two reactive sites, whereas those from monocots can be divided into two classes, one approximately 8 kDa in size with one reactive site (another reactive site was lost) and the other approximately 16 kDa in size with two reactive sites. The reactive site is located at unique exposed surfaces formed by a disulfide-linked beta-sheet loop that is highly conserved, rigid and mostly composed of nine residues. The structural features and molecular evolution of inhibitors are described, focusing on the conserved disulfide bridges. The sunflower trypsin inhibitor-1 (SFTI-1), with 14 amino acid residues, is a recently discovered bicyclic inhibitor, and is the most small and potent naturally occurring Bowman-Birk inhibitor. Recently, BBIs have become a hot topic because of their potential applications. BBIs are now used for defense against pathogens and insects in transgenic plants, which has advantages over using toxic and polluting insecticides. BBIs could also be applied in the prevention of cancer, Dengue fever, and inflammatory and allergic disorders, because of their inhibitory activity with respect to the serine proteases that play a pivotal role in the development and pathogenesis of these diseases. The canonical nine-residue loop of BBIs/STFI-1 provides an ideal template for drug design of specific inhibitors to target their respective proteases.