The entry of unclosed autophagosomes into vacuoles and its physiological relevance.

It is widely stated in the literature that closed mature autophagosomes (APs) fuse with lysosomes/vacuoles during macroautophagy/autophagy. Previously, we showed that unclosed APs accumulated as clusters outside vacuoles in Vps21/Rab5 and ESCRT mutants after a short period of nitrogen starvation. However, the fate of such unclosed APs remains unclear. In this study, we used a combination of cellular and biochemical approaches to show that unclosed double-membrane APs entered vacuoles and formed unclosed single-membrane autophagic bodies after prolonged nitrogen starvation or rapamycin treatment. Vacuolar hydrolases, vacuolar transport chaperon (VTC) proteins, Ypt7, and Vam3 were all involved in the entry of unclosed double-membrane APs into vacuoles in Vps21-mutant cells. Overexpression of the vacuolar hydrolases, Pep4 or Prb1, or depletion of most VTC proteins promoted the entry of unclosed APs into vacuoles in Vps21-mutant cells, whereas depletion of Pep4 and/or Prb1 delayed the entry into vacuoles. In contrast to the complete infertility of diploid cells of typical autophagy mutants, diploid cells of Vps21 mutant progressed through meiosis to sporulation, benefiting from the entry of unclosed APs into vacuoles after prolonged nitrogen starvation. Overall, these data represent a new observation that unclosed double-membrane APs can enter vacuoles after prolonged autophagy induction, most likely as a survival strategy.

A transcriptome-wide analysis provides novel insights into how Metabacillus indicus promotes coral larvae metamorphosis and settlement.

BACKGROUND: Coral reefs experience frequent and severe disturbances that can overwhelm their natural resilience. In such cases, ecological restoration is essential for coral reef recovery. Sexual reproduction has been reported to present the simplest and most cost-effective means for coral reef restoration. However, larval settlement and post-settlement survival represent bottlenecks for coral recruitment in sexual reproduction. While bacteria play a significant role in triggering coral metamorphosis and settlement in many coral species, the underlying molecular mechanisms remain largely unknown. In this study, we employed a transcriptome-level analysis to elucidate the intricate interactions between bacteria and coral larvae that are crucial for the settlement process. RESULTS: High Metabacillus indicus strain cB07 inoculation densities resulted in the successful induction of metamorphosis and settlement of coral Pocillopora damicoris larvae. Compared with controls, inoculated coral larvae exhibited a pronounced increase in the abundance of strain cB07 during metamorphosis and settlement, followed by a significant decrease in total lipid contents during the settled stage. The differentially expressed genes (DEGs) during metamorphosis were significantly enriched in amino acid, protein, fatty acid, and glucose related metabolic pathways. In settled coral larvae induced by strain cB07, there was a significant enrichment of DEGs with essential roles in the establishment of a symbiotic relationship between coral larvae and their symbiotic partners. The photosynthetic efficiency of strain cB07 induced primary polyp holobionts was improved compared to those of the negative controls. In addition, coral primary polyps induced by strain cB07 showed significant improvements in energy storage and survival. CONCLUSIONS: Our findings revealed that strain cB07 can promote coral larval settlement and enhance post-settlement survival and fitness. Manipulating coral sexual reproduction with strain cB07 can overcome the current recruitment bottleneck. This innovative approach holds promise for future coral reef restoration efforts.

Cognatishimia coralii sp. nov., a marine bacterium isolated from seawater surrounding corals.

Coral reefs are declining due to the rising seawater temperature. Bacteria within and surrounding corals play key roles in maintaining the homeostasis of the coral holobiont. Research on coral-related bacteria could provide benefits for coral reef restoration. During the isolation of coral-associated bacteria, a Gram-stain-negative, motile bacterium (D5M38T) was isolated from seawater surrounding corals in Daya Bay, Shenzhen, PR China. Phylogenetic analysis revealed that strain D5M38T represents a novel species in the genus Cognatishimia. The temperature range for strain D5M38T growth was 10-40 °C, and the optimum temperature was 37 °C. The salinity range for the growth of this isolate was from 0 to 4.0 %, with an optimal salinity level of 0.5 %. The pH range necessary for strain D5M38T growth was between pH 5.0 and 9.0, with an optimal pH being 7.5. The predominant fatty acid was summed feature 8 (65.0 %). The major respiratory quinone was Q-10. The DNA G+C content was 56.8 %. The genome size was 3.88 Mb. The average nucleotide identity (ANI), average amino acid identity (AAI) and digital DNA-DNA hybridization (dDDH) values between strain D5M38T and its two closest neighbours, Cognatishimia activa LMG 29900T and Cognatishimia maritima KCTC 23347T, were 73.2/73.6%, 73.2/73.6% and 19.7/19.5%, respectively. Strain D5M38T was clearly distinct from its closest neighbours C. activa LMG 29900T and C. maritima KCTC 23347T, with 16S rRNA gene sequence similarity values of 97.5 and 97.3 %, respectively. The phylogenetic analysis, along with the ANI, AAI, and dDDH values, demonstrated that strain D5M38T is a member of the genus Cognatishimia, and is distinct from the other two recognized species within this genus. The physiological, biochemical and chemotaxonomic characteristics also supported the species novelty of strain D5M38T. Thus, strain D5M38T is considered to be classified as representing a novel species in the genus Cognatishimia, for which the name Cognatishimia coralii sp. nov. is proposed. The type strain is D5M38T (=MCCC 1K08692T=KCTC 8160T).

Implementing a novel capture and ligation probe-PCR method in mass screen and treatment to support malaria elimination efforts in the China-Myanmar border region.

BACKGROUND: Mass screening and treatment (MSAT) for malaria elimination lacks an ideal diagnostic tool to allow sensitive and affordable test of the target population in the field. This study evaluated whether Capture and Ligation Probe-PCR (CLIP-PCR) could be used in a field MSAT in Laiza City, Myanmar. METHODS: On day 0, two dried blood spots were collected from each participant. On day 1, all samples were screened for Plasmodium in a 20 m2 laboratory with workbench, a biosafety cabinet, a refrigerator, a benchtop shaking incubator and a qPCR machine, by four technicians using CLIP-PCR with sample pooling, at a health clinic of the Chinese bordering town of Nabang. On day 2, all positives were followed up and treated. RESULTS: Of 15,038 persons (65% of the total population) screened, 204 (1.36%) were CLIP-PCR positives. Among them, 188, 14, and 2 were infected with Plasmodium vivax, Plasmodium falciparum, and P. vivax/P. falciparum mix, respectively. The testing capacity was 538 persons/day, with a cost of US$0.92 /person. The proportion of submicroscopic infection was 64.7%. All positive individuals received treatment within 72 h after blood collection. CONCLUSION: Using CLIP-PCR in MSAT in low transmission settings can support the malaria elimination efforts in the China-Myanmar border region.

Genetic diversity of transmission-blocking vaccine candidate antigens Pvs25 and Pvs28 in Plasmodium vivax isolates from China.

BACKGROUND: Transmission-blocking vaccines (TBVs) target the sexual stages of malaria parasites to reduce or interrupt the transmission cycle in human and mosquito populations. The genetic diversity of TBVs candidate antigens, Pvs25 and Pvs28, in Plasmodium vivax could provide evidence for the development of TBVs. METHODS: Dry blood spots from P. vivax patients were collected from Dandong, Suining, Hainan, Nyingchi, Tengchong, and Yingjiang in China. The pvs25 and pvs28 genes were amplified and sequenced. The genetic diversity of pvs25 and pvs28 were analyzed using DNASTAR, MEGA6, and DnaSP 5.0 programs. RESULTS: A total of 377 samples were collected, among which 324 and 272 samples were successfully amplified in the pvs25 and pvs28 genes, respectively. Eight haplotypes were identified in Pvs25, for which the predominant mutation was I130T with 100% prevalence. A variety of 22 haplotypes in Pvs28 were identified. The number of GSGGE/D repeats of Pvs28 was a range of 4-8, among which, high (7-8) and low (4-5) copy numbers of tandem repeats were found in haplotypes H2 and H17, respectively. The nucleotide diversity of pvs28 (π = 0.00305 ± 0.00061) was slightly higher than that of pvs25 (π = 0.00146 ± 0.00007), thus they were not significantly different (P > 0.05). The Tajima's D value of pvs25 was positive whereas pvs28 was negative, which indicated that both genes were affected by natural selection. CONCLUSION: The genetic diversity of pvs25 and pvs28 genes in China was relatively limited, which provided valuable information for TBVs design and optimization.

Knockdown of lncRNA IGF2BP2-AS1 inhibits proliferation and migration of oral squamous cell carcinoma cells via the Wnt/ß-catenin pathway.

BACKGROUND: Long non-coding RNA IGF2BP2 antisense RNA1 (lncRNA IGF2BP2-AS1) has been used to predict the overall survival rate of lung squamous cell carcinoma. This research aims to investigate the effect of IGF2BP2-AS1 in oral squamous cell carcinoma (OSCC). METHODS: The TCGA database was applied to evaluate the level of IGF2BP2-AS1 and its correlation with the clinicopathological characteristics of OSCC. The levels of IGF2BP2-AS1 in 30 OSCC and 20 normal tissue samples were detected by RT-qPCR. The distributions of IGF2BP2-AS1 in two OSCC cell lines (ie, Cal27 and SCC9) were detected by FISH. Colony formation, flow cytometry, wound-healing, transwell, and Western blotting analyses were used for evaluating the effect of IGF2BP2-AS1 on OSCC progression. RESULTS: In comparison with the normal tissue samples, OSCC showed higher expression of IGF2BP2-AS1. High expression of IGF2BP2-AS1 was associated with poor survival in OSCC patients. Results of FISH showed that IGF2BP2-AS1 was mainly present in the cytoplasm. Further in vitro functional tests demonstrated that downregulation of IGF2BP2-AS1 in Cal27 and SCC9 cells significantly inhibited cell proliferation and migration, leading to cell-cycle arrest and cell apoptosis. Western blotting showed that expressions of ß-catenin, Cyclin D1, Bcl-2, and MMP2 were downregulated, whereas Bax was upregulated following knockdown of IGF2BP2-AS1. The inhibitory effect of knockdown of IGF2BP2-AS1 on migration could be partially reversed by the Wnt/ß-catenin pathway stimulator LiCl. CONCLUSION: Our results suggest that knockdown of IGF2BP2-AS1 suppresses cell growth, migration and promotes apoptosis in OSCC cells, providing a new molecular target for OSCC.

Effectiveness of joint 3 + 1 malaria strategy along China-Myanmar cross border areas.

BACKGROUND: Cross-border malaria in Laiza City of Myanmar seriously affected Yingjiang County of China and compromised reaching the goal of malaria elimination by 2020. Since 2017, a pilot project on 3 + 1 strategy of joint cross-border malaria prevention and control was carried out for building a malaria buffer in these border areas. Here, 3 were the three preventive lines in China where different focalized approaches of malaria elimination were applied and + 1 was a defined border area in Myanmar where the integrated measures of malaria control were adopted. METHODS: A 5-year retrospective analysis (2015 to 2019) was conducted that included case detection, parasite prevalence and vector surveillance. Descriptive statistics was used and the incidence or rates were compared. The annual parasite incidence and the parasite prevalence rate in + 1 area of Myanmar, the annual importation rate in Yingjiang County of China and the density of An. minimus were statistically significant indictors to assess the effectiveness of the 3 + 1 strategy. RESULTS: In + 1 area of Myanmar from 2015 to 2019, the averaged annual parasite incidence was (59.11 ± 40.73)/1000 and Plasmodium vivax accounted for 96.27% of the total confirmed cases. After the pilot project, the annual parasite incidence dropped 89% from 104.77/1000 in 2016 to 12.18/1000 in 2019, the microscopic parasite prevalence rate dropped 100% from 0.34% in 2017 to zero in 2019 and the averaged density of An. Minimus per trap-night dropped 93% from 1.92 in June to 0.13 in September. The submicroscopic parasite prevalence rate increased from 1.15% in 2017 to 1.66% in 2019 without significant difference between the two surveys (P = 0.084). In Yingjiang County of China, neither indigenous nor introduced case was reported and 100% cases were imported from Myanmar since 2017. The averaged annual importation rate from 2015 to 2019 was (0.47 ± 0.15)/1000. After the pilot project, the annual importation rate dropped from 0.59/1000 in 2016 to 0.28/1000 in 2019 with an overall reduction of 53% in the whole county. The reduction was 67% (57.63/1000 to 18.01/1000) in the first preventive line, 52% (0.20/1000 to 0.10/1000) in the second preventive line and 36% (0.32/1000 to 0.22/1000) in the third preventive line. The averaged density of An. Minimus per trap-night in the first preventive line dropped 94% from 2.55 in June to 0.14 in September, without significant difference from that of + 1 area of Myanmar (Z value = - 1.18, P value = 0.24). CONCLUSION: The pilot project on 3 + 1 strategy has been significantly effective in the study areas and a buffer zone of border malaria was successfully established between Laiza City of Myanmar and Yingjiang County of China.

Allicin Protects against Cisplatin-Induced Stria Vascularis Damage: Possible Relation to Inhibition of Caspase-3 and PARP-1-AIF-Mediated Apoptotic Pathways.

Cisplatin is an anti-cancer drug that causes oxotoxic side effects such as impairment of inner ear function and hearing loss. We aimed to investigate the effects of allicin against cisplatin-induced stria vascularis damage in mice, and to clarify the mechanism underlying the protective effects of allicin against ototoxicity. Stria vascularis injury was induced in mice by intraperitoneal injection of cisplatin, which was significantly prevented by pretreatment with allicin. Allicin not only reduced cisplatin-activated expression of cleaved caspase-3 in marginal cells, PVM/Ms (perivascular resident macrophage-like melanocytes), and basal cells of the stria vascularis, but also decreased the expression of poly(ADP-ribose) polymerase-1 (PARP-1) and apoptosis-inducing factor (AIF) nuclear translocation in the stria vascularis cells. Our results demonstrate that allicin plays an effective role in protecting stria vascularis injury induced by cisplatin by inhibiting caspase-dependent, as well as caspase-independent PARP-1-AIF-mediated apoptotic pathways. Therefore, allicin may be useful in preventing cisplatin-induced ototoxicity.

Dietary supplementation with Rehmannia glutinosa affects the composition of intestinal microorganisms in common carp.

A feeding experiment was conducted to investigate the effects of Rehmannia glutinosa (RG) on the bacterial, archaeal, and fungal community composition in the gut of common carp (Cyprinus carpio L.). Common carp were given a control diet and an RG-supplemented diet (basal diet plus 4% prepared Rehmannia root powder) over a period of 80 days. Our results indicated that the bacteria Fusobacteria, Proteobacteria, and Bacteroidetes; the archaea Crenarchaeota and Euryarchaeota; and the fungi Basidiomycota are the most abundant microbial taxa in the gut of common carp. Compared with the common carp fed a control diet, the common carp fed an RG-supplemented diet contained a higher content of Akkermansia sp., and a lower proportion of Aeromonas sp. These results indicate that the consumption of a diet containing RG can lead to the accumulation of more beneficial microorganisms while inhibiting the growth of potential pathogens. Moreover, Crenarchaeota, the methanogenic, and Basidiomycota were detected in this study, these populations may be of high physiological relevance in carp because they have been implicated in human health and disease. Our results suggest that an RG-supplemented diet changes the intestinal microbial composition of common carp, which could have positive effects on the immune response of carp.

Receptivity to malaria in the China-Myanmar border in Yingjiang County, Yunnan Province, China.

BACKGROUND: The re-establishment of malaria has become an important public health issue in and out of China, and receptivity to this disease is key to its re-emergence. Yingjiang is one of the few counties with locally acquired malaria cases in the China-Myanmar border in China. This study aimed to understand receptivity to malaria in Yingjiang County, China, from June to October 2016. METHODS: Light-traps were employed to capture the mosquitoes in 17 villages in eight towns which were categorized into four elevation levels: level 1, 0-599 m; level 2, 600-1199 m; level 3, 1200-1799 m; and level 4, > 1800 m. Species richness, diversity, dominance and evenness were used to picture the community structure. Similarity in species composition was compared between different elevation levels. Data of seasonal abundance of mosquitoes, human biting rate, density of light-trap-captured adult mosquitoes and larvae, parous rate, and height distribution (density) of Anopheles minimus and Anopheles sinensis were collected in two towns (Na Bang and Ping Yuan) each month from June to October, 2016. RESULTS: Over the study period, 10,053 Anopheles mosquitoes were collected from the eight towns, and 15 Anopheles species were identified, the most-common of which were An. sinensis (75.4%), Anopheles kunmingensis (15.6%), and An. minimus (3.5%). Anopheles minimus was the major malaria vector in low-elevation areas (< 600 m, i.e., Na Bang town), and An. sinensis in medium-elevation areas (600-1200 m, i.e., Ping Yuan town). In Na Bang, the peak human-biting rate of An. minimus at the inner and outer sites of the village occurred in June and August 2016, with 5/bait/night and 15/bait/night, respectively. In Ping Yuan, the peak human-biting rate of An. sinensis was in August, with 9/bait/night at the inner site and 21/bait/night at the outer site. The two towns exhibited seasonal abundance with high density of the two adult vectors: The peak density of An. minimus was in June and that of An. sinensis was in August. Meanwhile, the peak larval density of An. minimus was in July, but that of An. sinensis decreased during the investigation season; the slightly acidic water suited the growth of these vectors. The parous rates of An. sinensis and An. minimus were 90.46 and 93.33%, respectively. CONCLUSIONS: The Anopheles community was spread across different elevation levels. Its structure was complex and stable during the entire epidemic season in low-elevation areas at the border. The high human-biting rates, adult and larval densities, and parous rates of the two Anopheles vectors reveal an exceedingly high receptivity to malaria in the China-Myanmar border in Yingjiang County.

[Evaluation on Malaria Hotspots in Yingjiang County of the China-Myanmar Border Area in 2015].

Objective: To understand the control status of malaria at hotspots in Yingjiang County and provide measures for malaria elimination in the China-Myanmar border areas of Yunnan Province. Methods: A survey was made in 4 villages with indigenous malaria cases or imported cases in Nabang and Tongbiguan of Yingjiang County in Yunnan Province in June and July 2015. Peripheral blood samples were collected from the neighboring residents around patients and examined by malaria rapid diagnostic test （RDT）. The results were further verified by nested-PCR. Mosquitoes were collected by overnight trapping with light traps in Jingpo, Lilisu, Jiema, and Mengxiangyang villages or by human landing catches in Jingpo and Lisu villages. Nested-PCR was performed on part of the captured Anopheles minimus to detect the malaria parasites. Results: One hundred and ninety-four filter blood samples were collected from 11 malaria cases in two sites. All were detected to be negative for Plasmodium by RDT. In contrast, two samples originated from Jingpo and Lisu villages with indigenous cases were detected to be positive for Plasmodium vivax by nested-PCR. A total of 2 374 mosquitoes were captured, belonging to 22 species of 4 genera: Anopheles, Culex, Aedes and Armigeres. The mosquitoes were predominated by genus Culex, followed by genus Anopheles（11.33%, 269/2 374） which was dominated by A. minimus（49.07%, 132/269）, then was A. sinensis（4.09%, 11/269）, A. maculatus（2.23%, 6/269）, A. jeyporiensis（0.74%, 2/269）and so on. The mean indoor man-biting rate of mosquitoes was 5.78 and 3.20 per person per hour for Jingpo and Lisu villages, and the mean outdoor man-biting rate of mosquitoes was 2.30 per person per hour for Lisu Village. The 14 A. minimus were negative for sporozoite infection as detected by nested-PCR. Conclusion: Nested-PCR showed that there are asymptomatic Plasmodium carriers in Yingjiang's border area of Yunnan Province. Four major mosquito species as malaria vectors exist with A. minimus as the dominant one.

Coverage, use and maintenance of bed nets and related influence factors in Kachin Special Region II, northeastern Myanmar.

BACKGROUND: Myanmar is one of the 31 highest burden malaria countries worldwide. Scaling up the appropriate use of insecticide-treated nets (ITNs) is a national policy for malaria prevention and control. However, the data on use, influencing factors and maintenance of bed nets is still lack among the population in Kachin Special Region II (KR2), Northeastern Myanmar. METHODS: The study combined a quantitative household questionnaire survey and qualitative direct observation of households. A Chi-squared test was used to compare the percentages of ownership, coverage, and rates of use of bed nets. Additionally, multivariate logistic regression analysis (MVLRA) was used to analyse factors that influence the use of bed nets. Finally, covariance compared the mean calibrated hole indexes (MCHI) across potential influence variables. RESULTS: The bed net to person ratio was 1:1.96 (i.e., more than one net for every two people). The long-lasting insecticidal net (LLIN) to person ratio was 1: 2.52. Also, the percentage of households that owned at least one bed net was 99.7% (666/688). Some 3262 (97.3%) residents slept under bed nets the prior night, 2551 (76.1%) of which slept under ITNs/LLINs the prior night (SUITNPN). The poorest families, those with thatched roofing, those who use agriculture as their main source of family income, household heads who knew that mosquitoes transmit malaria and those who used bed nets to prevent malaria, were significantly more likely to be in the SUITNPN group. However, residents in lowlands, and foothills were significantly less likely to be SUITNPNs. Finally, head of household attitude towards fixing bed nets influenced MCHI (F=8.09, P=0.0046). CONCLUSIONS: The coverage and usage rates of bed nets were high, especially among children, and pregnant women. Family wealth index, geographical zones, household roofing, source of family income, household head's knowledge of malaria transmission and of using bed nets as tools for malaria prevention are all independent factors which influence use of ITNs/LLINs in KR2. Maintaining high coverage, and use rate of bed nets should be a priority for the war-torn population of KR2 to ensure equity and human rights.

In vivo monitoring of dihydroartemisinin-piperaquine sensitivity in Plasmodium falciparum along the China-Myanmar border of Yunnan Province, China from 2007 to 2013.

BACKGROUND: Artemisinin-based combination therapy (ACT) is the recommended first-line treatment of falciparum malaria in all endemic countries. Artemisinin resistance in Plasmodium falciparum has been confirmed in the Greater Mekong subregion (GMS). Dihydroartemisinin-piperaquine (DAPQ) is the most commonly used ACT in China. To understand the DAPQ sensitivity of P. falciparum, DAPQ resistance was monitored in vivo along the China-Myanmar border from 2007 to 2013. METHODS: Eligible patients with mono-infections of P. falciparum were recruited to this study after obtaining full informed consent. DAPQ tablets for different categories of kg body weight ranges were given once a day for three days. Patients were followed up for 42 days. Polymerase chain reaction (PCR) was conducted to distinguish between re-infection and recrudescence, to confirm the Plasmodium species. The data were entered and analysed by the Kaplan-Meier method. Treatment outcome was assessed according to the WHO recommended standards. RESULTS: 243 patients were completed valid follow-up. The fever clearance time (FCT) and asexual parasite clearance times (APCT) were, respectively, 36.5 ± 10.9 and 43.5 ± 11.8 hours, and there was an increasing trend of both FCT (F = 268.41, P < 0.0001) and APCT (F = 88.6, P < 0.0001) from 2007 to 2013. Eight (3.3%, 95% confidence interval, 1.4-6.4%) patients present parasitaemia on day three after medication; however they were spontaneous cure on day four. 241 (99.2%; 95% CI, 97.1-99.9%) of the patients were adequate clinical and parasitological response (ACPR) and the proportions of ACPR had not changed significantly from 2007 to 2013 (X(2) = 2.81, P = 0.7288). CONCLUSION: In terms of efficacy, DAPQ is still an effective treatment for falciparum malaria. DAPQ sensitivity in P. falciparum had not significantly changed along the China-Myanmar border of Yunnan Province, China. However more attentions should be given to becoming slower fever and parasite clearance.

[Survey on Malaria Epidemics in China-Myanmar Border Area].

The malaria epidemics in Laza city of Myanmar and Yingjiang county in Yunnan province of China in 2012 and 2013 was reviewed retrospectively, and a survey on malaria infection was conducted in residents in the border areas. A total of 179 malaria cases were reported in Yingjiang county from 2012 to 2013, with an average annual incidence of 2.9 per 10,000. Of the 179 cases, 77.7% were imported cases and 22.3% were local cases; 79.3% were infected with Plasmodium vivax, 20.1% with P. falciparum, and 0.6% unidentified. In Laza city of Myanmar, 2,069 malaria cases were reported, with an average annual incidence of 322.5 per 10,000. Of them, 73.4% cases were infected with P. vivax, 20.1% with P. falciparum and 6.5% unidentified. In addition, the microscopic results revealed that the malaria parasite rate in the residents in Yingjiang county was 0%, while that in Laza city was 1.5%.

Monitoring Plasmodium vivax chloroquine sensitivity along China-Myanmar border of Yunnan Province, China during 2008-2013.

BACKGROUND: Plasmodium vivax is the most widespread of the malaria parasites infecting human hosts. In malaria-eliminating settings, both imported and local malaria predominantly occurs in border areas, and most of them are P. vivax. Chloroquine (CQ) is the first-line drug for P. vivax treatment in China. To understand CQ sensitivity in P. vivax, in vivo monitoring of CQ resistance was conducted along the China-Myanmar border from 2008 to 2013. METHODS: Eligible patients with mono-infections of P. vivax were recruited to this study after obtaining full informed consent. CQ tablets for different categories of kg body weight ranges were given once a day for three days. Patients were followed up for 28 days. PCR was conducted to distinguish between re-infection and recrudescence, to confirm the Plasmodium species. The data were entered and analysed by the Kaplan-Meier method. Treatment outcome and sensitivity were classified according to the WHO recommended standards. RESULTS: 603 patients were completed valid follow-up. The fever clearance time and asexual parasite clearance times were, respectively, 22.2 ± 10.2 and 38.1 ± 12.6 hours. 594 (98.5%) patients were adequate clinical and parasitological response (ACPR), and nine (1.5%) patients, who were late clinical failure (LCF) or resistant response level I (RI), were imported from the neighbouring districts of Myanmar. CONCLUSION: In terms of efficacy, CQ is still effective for vivax malaria treatment. Plasmodium vivax CQ sensitivity had not significantly changed along the China-Myanmar border of Yunnan Province, China.

Multistimuli-Responsive Shape-Memory Composites with a Water-Assisted Self-Healing Function Based on Sodium Carboxymethyl Cellulose/Poly(vinyl alcohol)/MXene.

Recent advancements in artificial intelligence have propelled the development of shape-memory polymers (SMPs) with sophisticated, environment-sensitive capabilities. Despite the progress, most of the existing SMPs are limited to responding to a single stimulus and show poor functionality, which has severely hindered their future applications. Herein, we report a high-performance multistimuli-responsive shape-memory and self-healing composite film fabricated by embedding MXene nanosheets into a conventional shape-memory sodium carboxymethyl cellulose (CMC) and poly(vinyl alcohol) (PVA) matrix. The incorporation of photothermal MXene nanosheets not only enhances the composite films' mechanical strength but also provides efficient solar-thermal conversion and robust light-actuated shape-memory properties. The resultant composite films exhibit an exceptional shape-memory response to various stimuli including heat, light, and water. Meanwhile, the interfacial interactions can be modulated by adjusting the MXene content, thereby enabling precise manipulation of the shape-memory performance. Moreover, thanks to the intrinsic hydrophilicity of the components and the unique physically cross-linked network, the composite films also demonstrate an effective water-assisted self-healing capability with an impressive healing efficiency of 85.7%. This work offers insights into the development of multifunctional, multistimuli-responsive shape-memory composites, opening up new possibilities for future applications in smart technologies.

Case report of a novel mutation in the TNC gene in Chinese patients with nonsyndromic hearing loss.

RATIONALE: Hereditary hearing loss is known to exhibit a significant degree of genetic heterogeneity. Herein, we present a case report of a novel mutation in the tenascin-C (TNC) gene in Chinese patients with nonsyndromic hearing loss (NSHL). PATIENT CONCERNS: This includes a young deaf couple and their 2-year-old baby. DIAGNOSES: Based on the clinical information, hearing test, metagenomic next-generation sequencing (mNGS), Sanger sequencing, protein function and structure analysis, and model prediction, in our case, the study results revealed 2 heterozygous mutations in the TNC gene (c.2852C>T, p.Thr951Ile) and the TBC1 domain family member 24 (TBC1D24) gene (c.1570C>T, p.Arg524Trp). These mutations may be responsible for the hearing loss observed in this family. Notably, the heterozygous mutations in the TNC gene (c.2852C>T, p.Thr951Ile) have not been previously reported in the literature. INTERVENTIONS: Avoid taking drugs that can cause deafness, wearing hearing AIDS, and cochlear implants. OUTCOMES: Regular follow-up of family members is ongoing. LESSONS: The genetic diagnosis of NSHL holds significant importance as it helps in making informed treatment decisions, providing prognostic information, and offering genetic counseling for the patient's family.

Cooperative Sentinel Surveillance of Malaria in Laiza and Nearby Areas of Myanmar and Importation Threat Monitoring - China, 2019-2023.

Introduction: Laiza and nearby areas (LNA) in Myanmar are identified as the primary malaria hotspots in the bordering regions of Yunnan Province, China. Methods: Six sentinel surveillance sites were established at the China-Myanmar border in LNA to monitor malaria. Data from 2019 was used as a baseline to analyze malaria incidence and trends in LNA and Myanmar, as well as the importation of malaria cases into China from 2019 to 2023. Results: Plasmodium vivax was the predominant species, representing 99.95% (14,060/14,066) of confirmed malaria cases in LNA. A total of 8,356 malaria cases were identified in 2023, with an annual parasite incidence (API) of 19.78 per 100 person-years. Compared to 2019, the incidence rate ratio was 21.47 (95% confidence interval: 18.84, 24.48), indicating that the API in 2023 was 21.47 times higher than that in 2019. In Yunnan, out of 1,016 reported cases, 545 imported cases (53.64%) originated from LNA and spread to 18 (13.95%) out of 129 counties. Ten provinces in China, including Yunnan, reported imported malaria cases from LNA in Myanmar. Conclusions: The increase in population, particularly among internally displaced persons, along with inadequate healthcare services, has led to a notable resurgence of malaria in LNA. This resurgence poses a risk to preventing the re-emergence of malaria transmission in China. There is an urgent need for novel collaborative policies, as well as financial and technical assistance, to enhance malaria control efforts in LNA, Myanmar.

Serological surveillance on potential Plasmodium vivax exposure risk in a post-elimination setting.

China was declared malaria free in June of 2021. In the post-elimination setting, vigilant surveillance is essential to sustain malaria free status. Serological surveillance has been recognized as an efficient tool for assessing the immunity levels and exposure risk in a population. In this study, a cross-sectional serological survey was conducted in Yingjiang County, China, in August-September, 2021. The study sites were villages along the borders with Myanmar, which have no local transmission since the last indigenous case registered in 2016. A total of 923 participants from six villages were enrolled. The majority was aged > 36 years (56.12%) and 12.46% (115/923) participants had experienced malaria infection at least once. A magnetic- bead-based assay was used to test antibodies against Plasmodium vivax antigen PvMSP-119 to evaluate the prevalence of antibody positive subjects. A reversible catalytic model was used to assess the risk of exposure. The prevalence of anti-PvMSP-119 IgG was 12.84% [95% confidence interval (CI): 9.22%-16.47%], 13.93% (95% CI: 10.11%-17.74%), and 3.57% (95% CI: 1.40%-5.75%) in three different line-of-defense areas, which differed significantly (P < 0.0001). The prevalence of anti-PvMSP-119 IgG increased with age and no statistically significant difference was detected between the sexes. The reversible catalytic model indicated that the seropositive conversion rate and seronegative reversion rate were 0.0042, 0.0034, 0.0032 and 0.0024, 0.0004, 0.0065 in the first-, second-line-of-defense area and total areas, respectively, and the fitted value did not differ significantly from the observed value (P > 0.1). Although this study found the prevalence of antibody-positive subjects and the seroconversion rate in this post-elimination setting were lower than that in transmission setting, the population still had an exposure risk. Serological surveillance should be considered in post-elimination settings to provide valuable information with which to evaluate the risk of malaria re-establishment.

Quality Characteristics of Reduced-Fat Emulsified Sausages Made with Yeast Mannoprotein Enzymatically Prepared with a ß-1,6-glucanase.

Mannoproteins, as yeast polysaccharides, have been utilized in food the industry as dietary fibers, emulsifying agents or fat replacers. Mannoprotein MP112, produced from yeast by enzymatic hydrolysis of myxobacterial ß-1,6-glucanase GluM, exhibits excellent emulsifying properties in emulsion preparation. In this study, we aimed to examine the application of stable emulsion with the addition of mannoprotein MP112 (MP112 emulsion) to reduce the fat content of sausages. The addition of MP112 emulsion in emulsified sausages significantly reduced the fat content and increased the moisture and protein contents of emulsified sausages without the expense of their good sensory quality. Moreover, the textural properties of sausages were markedly improved with the higher hardness, chewiness and cohesiveness, especially in the 50-75% replacement ratio of MP112 emulsion. On the other hand, MP112 emulsion replacement of animal fat markedly improved the nutritional composition of emulsified sausages; they displayed a higher PUFA/SFA ratio and lower n-6/n-3 ratio due to their saturated fatty acids being replaced by poly-unsaturated fatty acids. Meanwhile, the oxidative stability of sausages was improved linearly, corresponding to the increased replacement ratio of MP112 emulsion. Our results show that mannoprotein-based emulsions could be used as potential fat alternatives in developing reduced-fat meat products.